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Sample records for alpha-induced luteal regression

  1. Gelatinases, endonuclease and Vascular Endothelial Growth Factor during development and regression of swine luteal tissue

    PubMed Central

    Ribeiro, Luciana Andrea; Turba, Maria Elena; Zannoni, Augusta; Bacci, Maria Laura; Forni, Monica

    2006-01-01

    Background The development and regression of corpus luteum (CL) is characterized by an intense angiogenesis and angioregression accompanied by luteal tissue and extracellular matrix (ECM) remodelling. Vascular Endothelial Growth Factor (VEGF) is the main regulator of angiogenesis, promoting endothelial cell mitosis and differentiation. After the formation of neovascular tubes, the remodelling of ECM is essential for the correct development of CL, particularly by the action of specific class of proteolytic enzymes known as matrix metalloproteinases (MMPs). During luteal regression, characterized by an apoptotic process and successively by an intense ECM and luteal degradation, the activation of Ca++/Mg++-dependent endonucleases and MMPs activity are required. The levels of expression and activity of VEGF, MMP-2 and -9, and Ca++/Mg++-dependent endonucleases throughout the oestrous cycle and at pregnancy were analyzed. Results Different patterns of VEGF, MMPs and Ca++/Mg++-dependent endonuclease were observed in swine CL during different luteal phases and at pregnancy. Immediately after ovulation, the highest levels of VEGF mRNA/protein and MMP-9 activity were detected. On days 5–14 after ovulation, VEGF expression and MMP-2 and -9 activities are at basal levels, while Ca++/Mg++-dependent endonuclease levels increased significantly in relation to day 1. Only at luteolysis (day 17), Ca++/Mg++-dependent endonuclease and MMP-2 spontaneous activity increased significantly. At pregnancy, high levels of MMP-9 and VEGF were observed. Conclusion Our findings, obtained from a precisely controlled in vivo model of CL development and regression, allow us to determine relationships among VEGF, MMPs and endonucleases during angiogenesis and angioregression. Thus, CL provides a very interesting model for studying factors involved in vascular remodelling. PMID:17137503

  2. ATF3 Expression in the corpus luteum: possible role in luteal regression

    USDA-ARS?s Scientific Manuscript database

    The present study investigated the induction and possible role of activating transcription factor 3 (ATF3) in the corpus luteum. Postpubertal cattle were treated at midcycle with prostaglandin F2alpha(PGF) for 0–4 hours. Luteal tissue was processed for immunohistochemistry, in situ hybridization, an...

  3. Metabolomics study on primary dysmenorrhea patients during the luteal regression stage based on ultra performance liquid chromatography coupled with quadrupole‑time‑of‑flight mass spectrometry.

    PubMed

    Fang, Ling; Gu, Caiyun; Liu, Xinyu; Xie, Jiabin; Hou, Zhiguo; Tian, Meng; Yin, Jia; Li, Aizhu; Li, Yubo

    2017-03-01

    Primary dysmenorrhea (PD) is a common gynecological disorder which, while not life‑threatening, severely affects the quality of life of women. Most patients with PD suffer ovarian hormone imbalances caused by uterine contraction, which results in dysmenorrhea. PD patients may also suffer from increases in estrogen levels caused by increased levels of prostaglandin synthesis and release during luteal regression and early menstruation. Although PD pathogenesis has been previously reported on, these studies only examined the menstrual period and neglected the importance of the luteal regression stage. Therefore, the present study used urine metabolomics to examine changes in endogenous substances and detect urine biomarkers for PD during luteal regression. Ultra performance liquid chromatography coupled with quadrupole‑time‑of‑flight mass spectrometry was used to create metabolomic profiles for 36 patients with PD and 27 healthy controls. Principal component analysis and partial least squares discriminate analysis were used to investigate the metabolic alterations associated with PD. Ten biomarkers for PD were identified, including ornithine, dihydrocortisol, histidine, citrulline, sphinganine, phytosphingosine, progesterone, 17‑hydroxyprogesterone, androstenedione, and 15‑keto‑prostaglandin F2α. The specificity and sensitivity of these biomarkers was assessed based on the area under the curve of receiver operator characteristic curves, which can be used to distinguish patients with PD from healthy controls. These results provide novel targets for the treatment of PD.

  4. Metabolomics study on primary dysmenorrhea patients during the luteal regression stage based on ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry

    PubMed Central

    Fang, Ling; Gu, Caiyun; Liu, Xinyu; Xie, Jiabin; Hou, Zhiguo; Tian, Meng; Yin, Jia; Li, Aizhu; Li, Yubo

    2017-01-01

    Primary dysmenorrhea (PD) is a common gynecological disorder which, while not life-threatening, severely affects the quality of life of women. Most patients with PD suffer ovarian hormone imbalances caused by uterine contraction, which results in dysmenorrhea. PD patients may also suffer from increases in estrogen levels caused by increased levels of prostaglandin synthesis and release during luteal regression and early menstruation. Although PD pathogenesis has been previously reported on, these studies only examined the menstrual period and neglected the importance of the luteal regression stage. Therefore, the present study used urine metabolomics to examine changes in endogenous substances and detect urine biomarkers for PD during luteal regression. Ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was used to create metabolomic profiles for 36 patients with PD and 27 healthy controls. Principal component analysis and partial least squares discriminate analysis were used to investigate the metabolic alterations associated with PD. Ten biomarkers for PD were identified, including ornithine, dihydrocortisol, histidine, citrulline, sphinganine, phytosphingosine, progesterone, 17-hydroxyprogesterone, androstenedione, and 15-keto-prostaglandin F2α. The specificity and sensitivity of these biomarkers was assessed based on the area under the curve of receiver operator characteristic curves, which can be used to distinguish patients with PD from healthy controls. These results provide novel targets for the treatment of PD. PMID:28098892

  5. Induction of luteal regression in the marmoset monkey (Callithrix jacchus) by a gonadotrophin-releasing hormone antagonist and the effects on subsequent follicular development.

    PubMed

    Hodges, J K; Green, D I; Cottingham, P G; Sauer, M J; Edwards, C; Lightman, S L

    1988-03-01

    Doses of 100 or 200 micrograms of a novel GnRH antagonist ([N-acetyl-D beta Na11-D-pCl-Phe2-D-Phe3-D-Arg6-Phe7-Arg8-D-Ala10]NH2 GnRH) (4 animals/dose) were administered on Days 10/11 of the luteal phase and induced a marked suppression of circulating bioactive LH and progesterone concentrations within 1 day of treatment (P less than 0.01). Thereafter, progesterone concentrations remained low or undetectable until after the next ovulation. Similar results were obtained when 200 micrograms antagonist were given on Days 5/6 of the luteal phase (N = 4). The interval from injection of antagonist (200 micrograms but not 100 micrograms) to ovulation (based on a rise in progesterone above 10 ng/ml) was significantly longer than that from prostaglandin-induced luteal regression to ovulation in control cycles (N = 4/treatment) (range, 13-15 days after antagonist vs 8-10 days after prostaglandin, P less than 0.01). This delay of 4-5 days was equivalent to the duration for which LH concentrations were significantly suppressed by 200 micrograms antagonist when administered to ovariectomized animals (N = 3). Corpus luteum function during the cycle after GnRH antagonist treatment appeared normal according to the pattern of circulating progesterone. These results show that corpus luteum function and preovulatory follicular development in the marmoset monkey are dependent on pituitary gonadotrophin secretion.

  6. Influence of inducing luteal regression before a modified fixed-time artificial insemination protocol in postpartum beef cows on pregnancy success.

    PubMed

    Perry, G A; Perry, B L; Krantz, J H; Rodgers, J

    2012-02-01

    Most fixed-time insemination protocols utilize an injection of GnRH at the beginning of the protocol to initiate a new follicular wave. However, the ability of GnRH to initiate a new follicular wave is dependent on the stage of the estrous cycle. We hypothesized that administering PGF(2α) 3 d before initiating a fixed-time AI protocol would improve synchrony of follicular waves and result in greater pregnancy success. Therefore, our objective was to determine whether inducing luteal regression 3 d before a fixed-time AI protocol would improve control of follicular turnover and pregnancy success to fixed-time AI. Multiparous crossbred cows at 3 locations (n = 108, 296, and 97) were randomly assigned to 1 of 2 treatments: 1) PGF(2α) [25 mg; intramuscularly (i.m.)] on d -9, GnRH (100 μg; i.m.) and insertion of a controlled internal drug-releasing device (CIDR) on d -6, PGF(2α) (25 mg; i.m.) and CIDR removal with PGF(2α) (25 mg; i.m.) at CIDR removal on d 0 (PG-CIDR) or 2) GnRH (100 μg; i.m.) and insertion of a CIDR on d -5 and CIDR removal with PGF(2α) (25 mg; i.m.) at CIDR removal and 4 to 6 h after CIDR removal (5-d CIDR). Cows were time-inseminated between 66 and 72 h (PG-CIDR) or 70 to 74 h (5-d CIDR) after CIDR removal, and GnRH was administered at the time of fixed-time AI. At location 1, ovulatory response to the first injection of GnRH was determined by ultrasonography at the time of GnRH and 48 h after GnRH administration. Among cows with follicles ≥10 mm in diameter, more (P = 0.03) PG-CIDR-treated cows ovulated after the initial GnRH injection (88%, 43/49) compared with the 5-d CIDR-treated cows (68%, 34/50). Pregnancy outcome was not influenced by location (P = 0.96), age of the animal (P = 1.0), cycling status (P = 0.99), BCS (P = 1.0), or any 2-way interactions (P ≥ 0.13). However, pregnancy success was influenced by synchronization protocol (P = 0.04). Pregnancy outcome was greater (P = 0.04) for the PG-CIDR protocol (64%) compared with the 5

  7. Luteal blood flow and luteal function

    PubMed Central

    Takasaki, Akihisa; Tamura, Hiroshi; Taniguchi, Ken; Asada, Hiromi; Taketani, Toshiaki; Matsuoka, Aki; Yamagata, Yoshiaki; Shimamura, Katsunori; Morioka, Hitoshi; Sugino, Norihiro

    2009-01-01

    Background Blood flow in the corpus luteum (CL) is associated with luteal function. The present study was undertaken to investigate whether luteal function can be improved by increasing CL blood flow in women with luteal phase defect (LFD). Methods Blood flow impedance in the CL was measured by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a resistance index (RI). The patients with both LFD [serum progesterone (P) concentrations < 10 ng/ml during mid-luteal phase] and high CL-RI (≥ 0.51) were given vitamin-E (600 mg/day, n = 18), L-arginine (6 g/day, n = 14) as a potential nitric oxide donor, melatonin (3 mg/day, n = 13) as an antioxidant, or HCG (2,000 IU/day, n = 10) during the subsequent menstrual cycle. Results In the control group (n = 11), who received no medication to increase CL blood flow, only one patient (9%) improved in CL-RI and 2 patients (18%) improved in serum P. Vitamin-E improved CL-RI in 15 patients (83%) and improved serum P in 12 patients (67%). L-arginine improved CL-RI in all the patients (100%) and improved serum P in 10 patients (71%). HCG improved CL-RI in all the patients (100%) and improved serum P in 9 patients (90%). Melatonin had no significant effect. Conclusion Vitamin-E or L-arginine treatment improved luteal function by decreasing CL blood flow impedance. CL blood flow is a critical factor for luteal function. PMID:19144154

  8. Expression of Aldo-keto Reductase 1C23 in the Equine Corpus Luteum in Different Luteal Phases

    PubMed Central

    KOZAI, Keisuke; HOJO, Takuo; TOKUYAMA, Shota; SZÓSTEK, Anna Z; TAKAHASHI, Masashi; SAKATANI, Miki; NAMBO, Yasuo; SKARZYNSKI, Dariusz J; OKUDA, Kiyoshi

    2014-01-01

    Regression of the corpus luteum (CL) is characterized by a decay in progesterone (P4) production (functional luteolysis) and disappearance of luteal tissues (structural luteolysis). In mares, structural luteolysis is thought to be caused by apoptosis of luteal cells, but functional luteolysis is poorly understood. 20α-hydroxysteroid dehydrogenase (20α-HSD) catabolizes P4 into its biologically inactive form, 20α-hydroxyprogesterone (20α-OHP). In mares, aldo-keto reductase (AKR) 1C23, which is a member of the AKR superfamily, has 20α-HSD activity. To clarify whether AKR1C23 is associated with functional luteolysis in mares, we investigated the expression of AKR1C23 in the CL in different luteal phases. The luteal P4 concentration and levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA were higher in the mid luteal phase than in the late and regressed luteal phases (P<0.05), but the level of 3β-HSD protein was higher in the late luteal phase than in the regressed luteal phase (P<0.05). The luteal 20α-OHP concentration and the level of AKR1C23 mRNA were higher in the late luteal phase than in the early and mid luteal phases (P<0.05), and the level of AKR1C23 protein was also highest in the late luteal phase. Taken together, these findings suggest that metabolism of P4 by AKR1C23 is one of the processes contributing to functional luteolysis in mares. PMID:24492656

  9. Mifepristone for luteal phase contraception.

    PubMed

    Croxatto, Horacio B

    2003-12-01

    The concept of luteal phase contraception and the use of mifepristone in clinical trials, which allows for testing of its validity, as well as clinical pharmacological research designed to understand its mode of action, are reviewed. Early luteal phase administration has a variety of morphological, physiological and biochemical effects on the endometrium that are likely to interfere with embryonic-endometrial interactions. In fact, specifically designed pilot clinical trials as well as data derived from emergency contraception studies indicate that early luteal phase administration of mifepristone is highly effective in preventing pregnancy, with minimal disturbance of hormonal parameters or menstrual cyclicity. Mid and late luteal phase administration of mifepristone at doses above 25 mg are highly effective in inducing endometrial bleeding in nonconceptional cycles. However, administration of mifepristone within the period between implantation and expected menses fails to induce bleeding in a significant proportion of cases, and furthermore the bleeding induced does not insure the termination of pregnancy. While the data suggest there is potential for a once-a-month contraceptive pill, it is likely that no molecule endowed with partial agonistic properties, like mifepristone, will completely and reliably suppress the essential functions of progesterone in order to achieve contraceptive efficacy comparable to that of modern contraceptive methods.

  10. Emerging roles of immune cells in luteal angiogenesis.

    PubMed

    Shirasuna, Koumei; Shimizu, Takashi; Matsui, Motozumi; Miyamoto, Akio

    2013-01-01

    In the mammalian ovary, the corpus luteum (CL) is a unique transient endocrine organ displaying rapid angiogenesis and time-dependent accumulation of immune cells. The CL closely resembles 'transitory tumours', and the rate of luteal growth equals that of the fastest growing tumours. Recently, attention has focused on multiple roles of immune cells in luteal function, not only in luteolysis (CL disruption by immune responses involving T lymphocytes and macrophages), but also in CL development (CL remodelling by different immune responses involving neutrophils and macrophages). Neutrophils and macrophages regulate angiogenesis, lymphangiogenesis, and steroidogenesis by releasing cytokines in the CL. In addition, functional polarisation of neutrophils (proinflammatory N1 vs anti-inflammatory N2) and macrophages (proinflammatory M1 vs anti-inflammatory M2) has been demonstrated. This new concept concurs with the phenomenon of immune function within the luteal microenvironment: active development of the CL infiltrating anti-inflammatory N2 and M2 versus luteal regression together with proinflammatory N1 and M1. Conversely, excessive angiogenic factors and leucocyte infiltration result in indefinite disordered tumour development. However, the negative feedback regulator vasohibin-1 in the CL prevents excessive tumour-like vasculogenesis, suggesting that CL development has well coordinated time-dependent mechanisms. In this review, we discuss the physiological roles of immune cells involved in innate immunity (e.g. neutrophils and macrophages) in the local regulation of CL development with a primary focus on the cow.

  11. Transforming growth factor Beta 1 stimulates profibrotic activities of luteal fibroblasts in cows.

    PubMed

    Maroni, Dulce; Davis, John S

    2012-11-01

    Luteolysis is characterized by angioregression, luteal cell apoptosis, and remodeling of the extracellular matrix characterized by deposition of collagen 1. Transforming growth factor beta 1 (TGFB1) is a potent mediator of wound healing and fibrotic processes through stimulation of the synthesis of extracellular matrix components. We hypothesized that TGFB1 stimulates profibrotic activities of luteal fibroblasts. We examined the actions of TGFB1 on luteal fibroblast proliferation, extracellular matrix production, floating gel contraction, and chemotaxis. Fibroblasts were isolated from the bovine corpus luteum. Western blot analysis showed that luteal fibroblasts expressed collagen 1 and prolyl 4-hydroxylase but did not express markers of endothelial or steroidogenic cells. Treatment of fibroblasts with TGFB1 stimulated the phosphorylation of SMAD2 and SMAD3. [(3)H]thymidine incorporation studies showed that TGFB1 caused concentration-dependent reductions in DNA synthesis in luteal fibroblasts and significantly (P < 0.05) reduced the proliferative effect of FGF2 and fetal calf serum. However, TGFB1 did not reduce the viability of luteal fibroblasts. Treatment of luteal fibroblasts with TGFB1 induced the expression of laminin, collagen 1, and matrix metalloproteinase 1 as determined by Western blot analysis and gelatin zymography of conditioned medium. TGFB1 increased the chemotaxis of luteal fibroblasts toward fibronectin in a transwell system. Furthermore, TGFB1 increased the fibroblast-mediated contraction of floating bovine collagen 1 gels. These results suggest that TGFB1 contributes to the structural regression of the corpus luteum by stimulating luteal fibroblasts to remodel and contract the extracellular matrix.

  12. Bovine luteal prolactin receptor expression: potential involvement in regulation of progesterone during the estrous cycle and pregnancy.

    PubMed

    Thompson, I M; Ozawa, M; Bubolz, J W; Yang, Q; Dahl, G E

    2011-05-01

    In the present study, we performed quantitative reverse-transcription PCR (qPCR) to examine changes in gene expression of prolactin receptor (long form: l-PRLR; short form: s-PRLR) and 20α-hydroxysteroid dehydrogenase (20α-HSD; EC 1.1.1.149) in the bovine corpus luteum (CL) throughout the estrous cycle and pregnancy. Western blotting was used to determine protein abundance. Bovine CL were collected and luteal stages (n = 6/stage) were classified by macroscopic observation as early (d 1 to 4 after ovulation), mid (d 5 to 10), late (d 11 to 17), and regressing (d 18 to 20). A CL of pregnancy (n = 6) was determined by the presence of conceptus (d 28 to term). The mRNA for both forms of PRLR were expressed at all the luteal stages. Expression of s-PRLR and l-PRLR mRNA was less (P < 0.01) during early and regressing luteal stages compared with mid and late stages. Expression of s-PRLR mRNA in CL of pregnancy was greater (P < 0.01) than early, mid, and regressing CL and did not differ from late luteal stage expression. A greater (P < 0.01) expression of l-PRLR mRNA was observed in pregnant vs. early and regressing CL. In addition, qPCR showed the presence of 20α-HSD mRNA during all luteal stages of the estrous cycle, with the greatest (P < 0.01) expression observed in the regressing luteal stage. Western blotting revealed protein abundance of both PRLR isoforms during all luteal stages and pregnancy, with a predominance of the s-PRLR protein. Densitometry analysis indicated that protein abundances of s-PRLR were greater (P < 0.05) than l-PRLR during early, mid, and late luteal stages and did not differ during the regressing luteal stage. Protein abundances of 20α-HSD were least (P < 0.05) during the early luteal stage. In conclusion, results of the current study suggest a possible involvement of PRLR, especially s-PRLR, in the regulation of progesterone secretion and metabolism during the bovine estrous cycle and pregnancy.

  13. Gestating for 22 months: luteal development and pregnancy maintenance in elephants

    PubMed Central

    Lueders, Imke; Niemuller, Cheryl; Rich, Peter; Gray, Charlie; Hermes, Robert; Goeritz, Frank; Hildebrandt, Thomas B.

    2012-01-01

    The corpus luteum, a temporally established endocrine gland, formed on the ovary from remaining cells of the ovulated follicle, plays a key role in maintaining the early mammalian pregnancy by secreting progesterone. Despite being a monovular species, 2–12 corpora lutea (CLs) were found on the elephant ovaries during their long pregnancy lasting on average 640 days. However, the function and the formation of the additional CLs and their meaning remain unexplained. Here, we show from the example of the elephant, the close relationship between the maternally determined luteal phase length, the formation of multiple luteal structures and their progestagen secretion, the timespan of early embryonic development until implantation and maternal recognition. Through three-dimensional and Colour Flow ultrasonography of the ovaries and the uterus, we conclude that pregnant elephants maintain active CL throughout gestation that appear as main source of progestagens. Two LH peaks during the follicular phase ensure the development of a set of 5.4 ± 2.7 CLs. Accessory CLs (acCLs) form prior to ovulation after the first luteinizing hormone (LH) peak, while the ovulatory CL (ovCL) forms after the second LH peak. After five to six weeks (the normal luteal phase lifespan), all existing CLs begin to regress. However, they resume growing as soon as an embryo becomes ultrasonographically apparent on day 49 ± 2. After this time, all pregnancy CLs grow significantly larger than in a non-conceptive luteal phase and are maintained until after parturition. The long luteal phase is congruent with a slow early embryonic development and luteal rescue only starts ‘last minute’, with presumed implantation of the embryo. Our findings demonstrate a highly successful reproductive solution, different from currently described mammalian models. PMID:22719030

  14. Improving the luteal phase after ovarian stimulation: reviewing new options.

    PubMed

    Yding Andersen, C; Vilbour Andersen, K

    2014-05-01

    The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using the GnRHa trigger suggest an association between the reproductive outcome after IVF treatment and the mid-luteal-phase serum progesterone concentration. It appears that a minimum mid-luteal progesterone threshold of approximately 80-100 nmol/l exists, which, when surpassed, results in reduced early pregnancy loss and an increased live birth rate. Further, the trade off between the HCG bolus and the subsequent risk of ovarian hyperstimulation syndrome has resulted in a trend to reduce the HCG bolus from 10,000 IU to 6500-5000 IU, which augments the HCG/LH deficiency during the early/mid-luteal phase. The mid-luteal HCG/LH shortage results in an altered progesterone profile, showing the highest concentration during the early luteal phase, contrasting with the mid-luteal peak seen in the natural menstrual cycle. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  15. Prospective evaluation of luteal phase length and natural fertility.

    PubMed

    Crawford, Natalie M; Pritchard, David A; Herring, Amy H; Steiner, Anne Z

    2017-03-01

    To evaluate the impact of a short luteal phase on fecundity. Prospective time-to-pregnancy cohort study. Not applicable. Women trying to conceive, ages 30-44 years, without known infertility. Daily diaries, ovulation prediction testing, standardized pregnancy testing. Subsequent cycle fecundity. Included in the analysis were 1,635 cycles from 284 women. A short luteal phase (≤11 days including the day of ovulation) occurred in 18% of observed cycles. Mean luteal phase length was 14 days. Significantly more women with a short luteal phase were smokers. After adjustment for age, women with a short luteal phase had 0.82 times the odds of pregnancy in the subsequent cycle immediately following the short luteal phase compared with women without a short luteal phase. Women with a short luteal length in the first observed cycle had significantly lower fertility after the first 6 months of pregnancy attempt, but at 12 months there was no significant difference in cumulative probability of pregnancy. Although an isolated cycle with a short luteal phase may negatively affect short-term fertility, incidence of infertility at 12 months was not significantly higher among these women. NCT01028365. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Evaluation of bovine luteal blood flow by using color Doppler ultrasonography.

    PubMed

    Lüttgenau, J; Bollwein, H

    2014-04-01

    Since luteal vascularization plays a decisive role for the function of the corpus luteum (CL), the investigation of luteal blood flow (LBF) might give valuable information about the physiology and patho-physiology of the CL. To quantify LBF, usually Power mode color Doppler ultrasonography is used. This method detects the number of red blood cells moving through the vessels and shows them as color pixels on the B-mode image of the CL. The area of color pixels is measured with computer-assisted image analysis software and is used as a semiquantitative parameter for the assessment of LBF. Although Power mode is superior for the evaluation of LBF compared to conventional color Doppler ultrasonography, which detects the velocity of blood cells, it is still not sufficiently sensitive to detect the blood flow in the small vessels in the center of the bovine CL. Therefore, blood flow can only be measured in the bigger luteal vessels in the outer edge of the CL. Color Doppler ultrasonographic studies of the bovine estrous cycle have shown that plasma progesterone (P4) concentration can be more reliably predicted by LBF than by luteal size (LS), especially during the CL regression. During the midluteal phase, cows with low P4 level showed smaller CL, but LBF, related to LS, did not differ between cows with low and high P4 levels. In contrast to non-pregnant cows, a significant rise in LBF was observed three weeks after insemination in pregnant cows. However, LBF was not useful for an early pregnancy diagnosis due to high LBF variation among cows. When the effects of an acute systemic inflammation and exogenous hormones on the CL are examined, the LBF determination is more sensitive than LS assessment. In conclusion, color Doppler ultrasonography of the bovine CL provides additional information on luteal function compared to measurements of LS and plasma P4, but its value as a parameter concerning assessment of fertility in cows has to be clarified.

  17. Transcriptomes of bovine ovarian follicular and luteal cells

    USDA-ARS?s Scientific Manuscript database

    RNA expression analysis was performed on four somatic ovarian cell types using a gene array panel: the granulosa cells (GCs) and theca cells (TCs) of the dominant follicle and the large luteal cells (LLCs) and small luteal cells (SLCs) of the corpus luteum. The normalized linear microarray data was ...

  18. Treatment of luteal phase defects in assisted reproduction.

    PubMed

    Muñoz, Elkin; Taboas, Esther; Portela, Susana; Aguilar, Jesús; Fernandez, Iria; Muñoz, Luis; Bosch, Ernesto

    2013-07-01

    Abnormal luteal function is a common issue in assisted reproduction techniques associated with ovarian stimulation probably due to low levels of LH in the middle and in the late luteal phase. This defect seems to be associated with supraphysiological steroid levels at the end of follicular phase. The luteal phase insufficiency has not got a diagnostic test which has proven reliable in a clinical setting. Luteal phase after ovarian stimulation becomes shorter and insufficient, resulting in lower pregnancy rates. Luteal phase support with progesterone or hCG improves pregnancy outcomes and no differences are found among different routes of administration. However, hCG increases the risk of ovarian hyperstimulation syndrome. In relation to the length of luteal support, the day of starting it remains controversial and it does not seem necessary to continue once a pregnancy has been established. After GnRHa triggering ovulation, intensive luteal support or hCG bolus can overcome the defect in luteal phase, but more studies are needed to show the LH utility as support.

  19. Corpora lutea of pregnant and pseudopregnant domestic cats reveal similar steroidogenic capacities during the luteal life span.

    PubMed

    Zschockelt, Lina; Amelkina, Olga; Siemieniuch, Marta J; Koster, Stefanie; Jewgenow, Katarina; Braun, Beate C

    2014-10-01

    luteal stages of pseudopregnancy. Concentrations of P4 were higher in the development/maintenance compared to the regression stages (p=0.01). We conclude that cat CL of the same histomorphological stage are characterised by identical steroidogenic capacities independently of an on-going pregnancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Effects of testosterone and 5alpha-dihydrotestosterone on luteal lifespan in dairy heifers.

    PubMed

    Silvia, W J; Jacobs, A L; Hayes, S H

    1989-11-01

    Endogenous concentrations of testosterone increase approximately 7 d prior to estrus in cattle and goats. Inhibition of testosterone synthesis results in a delay of luteal regression in both species. The purpose of this experiment was to determine if treatment with testosterone or 5alpha-dihydrotestosterone (DHT), 2 to 6 d prior to the endogenous rise in testosterone, would result in premature luteal regression. Sixteen heifers were randomly assigned to one of three treatment groups: 1) Control (n = 6); 2) testosterone (100 mug, n = 5); or 3) DHT (100 mug, n = 5). Each heifer received a single injection of the appropriate steriod on Day 8, 9, 10, 11 or 12 post estrus. Jugular venous blood samples were collected at frequent intervals for 24 h to quantify testosterone, and then daily for 14 d to quantify progesterone. Concentrations of testosterone increased within 15 min of injection of testosterone, and reached a maximum at 30 min. Concentrations were maintained at > 2 ng/ml throughout the first 24 h after injection. Based on concentrations of progesterone, neither androgen had any effect on the lifespan of the corpus luteum or the level of luteal function.

  1. Isolation and functional aspects of free luteal cells

    SciTech Connect

    Luborsky, J.L.; Berhrman, H.R.

    1985-01-01

    Methods of luteal cell isolation employ enzymatic treatment of luteal tissue with collagenase and deoxyribonuclease. Additional enzymes such as hyaluronidase or Pronase are also used in some instances. Isolated luteal cells retain the morphological characteristics of steroid secreting cells after isolation. They contain mitochondria, variable amounts of lipid droplets, and an extensive smooth endoplasmic reticulum. Isolated luteal cells have been used in numerous studies to examine the regulation of steriodogenesis by luteinizing hormone (LH). LH receptor binding studies were employed to quantitate specific properties of hormone-receptor interaction in relation to cellular function. Binding of (/sup 125/I)LH to bovine luteal cells and membranes was compared and it was concluded that the enzymatic treatment used to isolate cells did not change the LH receptor binding kinetics.

  2. Histological and endocrine characterisation of the annual luteal activity in Eurasian lynx (Lynx lynx).

    PubMed

    Carnaby, Kim; Painer, Johanna; Söderberg, Arne; Gavier-Widèn, Dolores; Göritz, Frank; Dehnhard, Martin; Jewgenow, Katarina

    2012-10-01

    Lynx presents a unique sexual cycle with persistent corpora lutea (CLs) and elevated serum progesterone (P₄) throughout parturition and lactation. In other mammals, CLs normally disintegrate after parturition, therefore the aim of our study was to characterise the annual life cycle of lynx CLs. Ovaries from Eurasian lynxes were obtained from the National Veterinary Institute in Sweden, where tissues from killed lynx were stored at -20 °C. Ovaries from 66 animals were weighed; each corpus luteum was segmented for histology and hormone analysis. Ovary and CLs weights were constant throughout the year, peaking during pregnancy. In non-pregnant lynxes, the seasonal level of intraluteal steroids was steady for P₄ (3.2±1.9 s.d. μg/g, n=53) and total oestrogens (18.3±15.5 s.d. ng/g, n=53). Within histology slides, structurally intact luteal cells were found throughout the year with the highest incidence in March/April; evidence of luteal regression was predominantly found in post-breeding season. Ovaries from pregnant animals contained two types of CLs. Group A was bigger in size with large luteal cells (P₄, 72.3±65.4 s.d. μg/g; oestrogen, 454.0±52.4 s.d. ng/g). In contrast, group B were smaller, with greater luteal regression and lower steroid concentrations (P₄, 8.3±2.9 s.d. μg/g; oestrogen, 31.5±20.4 s.d. ng/g). Our results suggest that structural luteolysis proceeds throughout the year and into next breeding cycle, resulting in two CLs types on the same ovary.

  3. The bovine luteal histological composition: a topographic point of view.

    PubMed

    Cools, S; Van den Broeck, W; De Vliegher, S; Piepers, S; Opsomer, G

    2013-04-01

    High-yielding dairy cows are struggling with a high incidence of embryonic loss, among others caused by an insufficient peripheral progesterone concentration which for its part might be associated with an impaired luteal progesterone production. This impaired capacity to produce progesterone might be reflected in the histology of the gland. The aim of the present pilot study was the assessment of the variation in cell density within a bovine luteal gland (LG), to examine whether it is possible to analyse histologically the functionality of the gland based on one single tissue sample. Six LGs (stage II or III) were harvested out of just as many healthy cows at the slaughterhouse. The luteal cell density was assessed by calculating the nuclear density (ND) of the different luteal cell types on haematoxylin-eosin-stained histological sections from a number of topographic regions evenly spread throughout the glands, to give an overview of the pattern of cellular distribution within the whole gland. Cells were differentiated into 'large luteal cells', 'small luteal cells' and 'non-steroidogenic cells'. Results show that the cellular density, within a tissue sample is not significantly influenced by its location in relation to the gland's equatorial plane. However, the position with respect to the polar axis of the gland has a decisive effect, as the ND is significantly higher (p < 0.05) in the peripheral regions (outer zone) when compared with the central regions (inner zone) of the gland, and this counts for all three cell types.

  4. Spectral Measurements of Alpha-induced Radioluminescence in Various Gases

    DOE PAGES

    Brett, Jaclyn; Koehler, Katrina Elizabeth; Bischak, Michael; ...

    2017-09-06

    Radioluminescent emission in Ar, N2, O2, and dry air at P=1 atm was observed induced by 5 MeV α particles. The wavelength range with a single detector spanned 250–1100 nm, extending the range well into the UV and IR bands with a single detector. Measured spectral lines for alpha-induced luminescence were corrected for detector transmission and intensities compared to previous work. The exploration of multiple gases over a wide frequency range opens the door to security and remote sensing applications, where different environments are routinely encountered. Finally, this work provides spectra that can be used in guiding future filter developmentmore » focusing on remote alpha detection.« less

  5. The effect of metritis on luteal function in dairy cows

    PubMed Central

    2013-01-01

    Background Disturbed uterine involution impairs ovarian function in the first weeks after calving. This study analyzed the long-term effect of metritis on luteal function of 47 lactating Holstein-Friesian cows during the first four postpartum estrous cycles. Cows with abnormal uterine enlargement and malodorous lochia were classified as having metritis (group M, n = 18), and all others were considered healthy (group H, n = 29). Luteal size was measured once between days 9 and 13 of the first (group H, n = 11; group M, n = 12), second (group H, n = 23; group M, n = 18) and fourth (group H, n = 11; group M, n = 7) postpartum luteal phases. Serum progesterone concentration was measured at the same time. Sixteen cows (group H, n = 9; group M, n = 7) underwent transvaginal luteal biopsy for gene expression analysis of steroidogenic regulatory proteins during the second and fourth cycles. Cows with persistence of the corpus luteum (CL) underwent determination of luteal size, luteal biopsy and serum progesterone measurement once between days 29 and 33, followed by prostaglandin treatment to induce luteolysis. The same procedures were repeated once between days 9 and 13 of the induced cycle. Results The cows in group M had smaller first-cycle CLs than the cows in group H (p = 0.04), but progesterone concentrations did not differ between groups. Luteal size, progesterone concentration and gene expression did not differ between the two groups during the second and fourth cycles. Compared with healthy cows (10%), there was a trend (p = 0.07) toward a higher prevalence of persistent CLs in cows with metritis (33%). Persistent CLs were limited to the first cycle. Persistent CLs and the induced cyclic CLs did not differ with regard to the variables investigated. Conclusions An effect of metritis on luteal activity was apparent in the first postpartum estrous cycle. However, after the first postpartum cycle, no differences occurred

  6. Establishment and characterization of a telomerase immortalized porcine luteal cells.

    PubMed

    Zhang, Liang; Huang, Yong; Wang, Zhenyu; Luo, Xiaomao; Zhang, Hongling; Du, Qian; Chang, Lingling; Zhao, Xiaomin; Tong, Dewen

    2017-05-01

    Luteal cells play a crucial role in pregnancy through secreting progesterone to maintain pregnancy and support of fetus. However, low cellular yields and inability to passage primary porcine luteal cells (PLCs) in vitro limit the luteal cell study. Therefore, developing an immortalized porcine luteal cell line is necessary for studying luteal cells activity and function in different diseases. In this study, primary PLCs were obtained from gilts at day 30 to day 50 of gestation and immortalized by human telomerase reverse transcriptase (hTERT). The porcine corpus luteal cell line (hTERT-PLCs) expressed hTERT gene steady, maintained high hTERT activity and normal karyotype. The phase contrast microscope and transmission electron microscope observation showed primary PLCs and hTERT-PLCs were polygonal and exhibited abundant mitochondria, smooth endoplasmic reticulum and lipid droplets. 3β hydroxysteroid dehydrogenase (3βHSD) and Oil-Red-O staining showed that hTERT-PLCs at passage 30 and 50 were similar to primary PLCs. The hTERT-PLCs expressed steroidogenesis-related proteins, enzymes and receptors, such as steroidogenic acute regulatory protein, P450 cholesterol side-chain cleavage, 3βHSD, 20αHSD, luteinizing hormone receptor, progesterone receptor, prolactin receptor, estrogen receptorα/β, as well as primary PLCs. Consequently, hTERT-PLCs could secret progesterone and exhibited similar responses to luteinizing hormone and prostaglandin F2α as primary PLCs. In addition, the hTERT-PLCs did not show neoplastic transformation or anchorage independent growth. In summary, we developed an immortalized porcine luteal cell line which maintained its originally morphological, biological and functional characteristics. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Involvement of Mst1 in tumor necrosis factor-{alpha}-induced apoptosis of endothelial cells

    SciTech Connect

    Ohtsubo, Hideki; Ichiki, Toshihiro Imayama, Ikuyo; Ono, Hiroki; Fukuyama, Kae; Hashiguchi, Yasuko; Sadoshima, Junichi; Sunagawa, Kenji

    2008-03-07

    Mammalian sterile 20-kinase 1 (Mst1), a member of the sterile-20 family protein kinase, plays an important role in the induction of apoptosis. However, little is know about the physiological activator of Mst1 and the role of Mst1 in endothelial cells (ECs). We examined whether Mst1 is involved in the tumor necrosis factor (TNF)-{alpha}-induced apoptosis of ECs. Western blot analysis revealed that TNF-{alpha} induced activation of caspase 3 and Mst1 in a time- and dose-dependent manner. TNF-{alpha}-induced Mst1 activation is almost completely prevented by pretreatment with Z-DEVD-FMK, a caspase 3 inhibitor. Nuclear staining with Hoechst 33258 and fluorescence-activated cell sorting of propidium iodide-stained cells showed that TNF-{alpha} induced apoptosis of EC. Diphenyleneiodonium, an inhibitor of NADPH oxidase, and N-acetylcysteine, a potent antioxidant, also inhibited TNF-{alpha}-induced activation of Mst1 and caspase 3, as well as apoptosis. Knockdown of Mst1 expression by short interfering RNA attenuated TNF-{alpha}-induced apoptosis but not cleavage of caspase 3. These results suggest that Mst1 plays an important role in the induction of TNF-{alpha}-induced apoptosis of EC. However, positive feedback mechanism between Mst1 and caspase 3, which was shown in the previous studies, was not observed. Inhibition of Mst1 function may be beneficial for maintaining the endothelial integrity and inhibition of atherogenesis.

  8. Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.

    PubMed

    Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog-Bon; Lee, Sang-Rae; Kong, Il-Keun; Ryoo, Jae-Woong; Park, Young-Il; Chang, Kyu-Tae; Lee, Dong-Seok

    2014-09-15

    We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Notch Signaling Pathway Regulates Progesterone Secretion in Murine Luteal Cells.

    PubMed

    Wang, Jing; Liu, Shuangmei; Peng, Lichao; Dong, Qiming; Bao, Riqiang; Lv, Qiulan; Tang, Min; Hu, Chuan; Li, Gang; Liang, Shangdong; Zhang, Chunping

    2015-10-01

    Notch signaling is an evolutionarily conserved pathway, which involves in various cell life activities. Other studies and our report showed that the Notch signaling plays very important role in follicle development in mammalian ovaries. In luteal cells, Notch ligand, delta-like ligand 4, is involved in normal luteal vasculature. In this study, murine luteal cells were cultured in vitro and treated with Notch signaling inhibitors, L-658,458 and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT). We found that L-658,458 and DAPT treatment decrease basal and human chorionic gonadotropin (hCG)-stimulated progesterone secretion. On the contrary, overexpression of intracellular domain of Notch3 increased basal and hCG-stimulated progesterone secretion. Further studies demonstrated that Notch signaling regulated the expression of steroidogenic acute regulatory protein and CYP11A, 2 key enzymes for progesterone synthesis. In conclusion, Notch signaling plays important role in regulating progesterone secretion in murine luteal cells.

  10. The clinical relevance of luteal phase deficiency: a committee opinion.

    PubMed

    2012-11-01

    Luteal phase deficiency (LPD) has been described in healthy normally menstruating women and in association with other medical conditions. While progesterone is important for the process of implantation and early embryonic development, LPD, as an independent entity causing infertility, has not been proven. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Transcriptomes of bovine ovarian follicular and luteal cells.

    PubMed

    Romereim, Sarah M; Summers, Adam F; Pohlmeier, William E; Zhang, Pan; Hou, Xiaoying; Talbott, Heather A; Cushman, Robert A; Wood, Jennifer R; Davis, John S; Cupp, Andrea S

    2017-02-01

    Affymetrix Bovine GeneChip® Gene 1.0 ST Array RNA expression analysis was performed on four somatic ovarian cell types: the granulosa cells (GCs) and theca cells (TCs) of the dominant follicle and the large luteal cells (LLCs) and small luteal cells (SLCs) of the corpus luteum. The normalized linear microarray data was deposited to the NCBI GEO repository (GSE83524). Subsequent ANOVA determined genes that were enriched (≥2 fold more) or decreased (≤-2 fold less) in one cell type compared to all three other cell types, and these analyzed and filtered datasets are presented as tables. Genes that were shared in enriched expression in both follicular cell types (GCs and TCs) or in both luteal cells types (LLCs and SLCs) are also reported in tables. The standard deviation of the analyzed array data in relation to the log of the expression values is shown as a figure. These data have been further analyzed and interpreted in the companion article "Gene expression profiling of ovarian follicular and luteal cells provides insight into cellular identities and functions" (Romereim et al., 2017) [1].

  12. Osmotic stress sensitizes naturally resistant cells to TNF-alpha-induced apoptosis.

    PubMed

    Franco, D L; Nojek, I M; Molinero, L; Coso, O A; Costas, M A

    2002-10-01

    Most cells are naturally resistant to TNF-alpha-induced cell death and become sensitized when NF-kappaB transactivation is blocked or in the presence of protein synthesis inhibitors that prevent the expression of anti-apoptotic genes. In this report we analyzed the role of osmotic stress on TNF-alpha-induced cell death. We found that it sensitizes the naturally resistant HeLa cells to TNF-alpha-induced apoptosis, with the involvement of an increase in the activity of several kinases, the inhibition of Bcl-2 expression, and a late increase on NF-kappaB activation. Cell death occurs regardless of the enhanced NF-kappaB activity, whose inhibition produces an increase in apoptosis. The inhibition of p38 kinase, also involved in NF-kappaB activation, significantly increases the effect of osmotic stress on TNF-alpha-induced cell death.

  13. Expression of GnRH receptor in the canine corpus luteum, and luteal function following deslorelin acetate-induced puberty delay.

    PubMed

    Kaya, D; Gram, A; Kowalewski, M P; Schäfer-Somi, S; Kuru, M; Boos, A; Aslan, S

    2017-09-30

    The goals of this study were as follows: (Experiment 1) to examine the basic capability of canine corpora lutea (CL) to respond to GnRH by assessing expression of gonadotropin-releasing hormone receptor (GnRH-R) in luteal samples collected throughout the luteal lifespan from non-pregnant dogs, and (Experiment 2) to investigate the effects of pre-pubertal application of the GnRH agonist deslorelin acetate on luteal function following the first oestrus. Mature CL were collected during the mid-luteal phase (days 30-45) from treated and control bitches. Transcript levels of several factors were determined: estrogen receptors (ESR1/ERα, ESR2/ERβ), progesterone (P4)-receptor (PGR), prolactin receptor (PRLR), PGE2-synthase (PTGES) and PGE2 receptors (PTGER2/EP2, PTGER4/EP4), vascular endothelial growth factor (VEGFA) and VEGF receptors (VEGFR1 and VEGFR2), cyclooxygenase 2 (COX2/PTGS2), steroidogenic acute regulatory protein (STAR) and 3β-hydroxysteroid dehydrogenase (3βHSD). Additionally, levels of Kisspeptin 1 (Kiss1) and its receptor (KISS1-R) were evaluated. Although generally low, GnRH-R expression was time dependent and was elevated during early dioestrus, with a significant decrease towards luteal regression. In deslorelin-treated and control dogs, its expression was either low or frequently below the detection limit. EP2 and VEGFR1 were higher in the treated group, which could be caused by a feedback mechanism after long-term suppression of reproductive activity. Despite large individual variations, 3βHSD was higher in the deslorelin-treated group. This, along with unchanged STAR expression, was apparently not mirrored in increased luteal functionality, because similar P4 levels were detected in both groups. Finally, the deslorelin-mediated long-term delay of puberty does not have negative carry-over effects on subsequent ovarian functionality in bitches. © 2017 Blackwell Verlag GmbH.

  14. A novel physiological culture system that mimics luteal angiogenesis.

    PubMed

    Robinson, R S; Hammond, A J; Mann, G E; Hunter, M G

    2008-03-01

    Luteal inadequacy is a major cause of poor embryo development and infertility. Angiogenesis, the formation of new blood vessels, is an essential process underpinning corpus luteum (CL) development and progesterone production. Thus, understanding the factors that regulate angiogenesis during this critical time is essential for the development of novel strategies to alleviate luteal inadequacy and infertility. This study demonstrates the development of a physiologically relevant primary culture system that mimics luteal angiogenesis. This system incorporates all luteal cell types (e.g. endothelial, steroidogenic cells, fibroblasts and pericytes). Using this approach, endothelial cells, identified by the specific marker von Willebrand factor (VWF), start to form clusters on day 2, which then proliferate and develop thread-like structures. After 9 days in culture, these tubule-like structures lengthen, thicken and form highly organized intricate networks resembling a capillary bed. Development of the vasculature was promoted by coating wells with fibronectin, as determined by image analysis (P<0.001). Progesterone production increased with time and was stimulated by LH re-enforcing the physiological relevance of the model in mimicking in vivo luteal function. LH also increased the area stained positively for VWF by twofold (P<0.05). Development of this endothelial cell network was stimulated by fibroblast growth factor 2 and vascular endothelial growth factor A, which increased total area of VWF positive staining on day 9, both independently (three- to fourfold; P<0.01) and in combination (tenfold; P<0.001). In conclusion, the successful development of endothelial cell networks in vitro provides a new opportunity to elucidate the physiological control of the angiogenic process in the developing CL.

  15. Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor positive breast cancer

    PubMed Central

    Love, Richard R.; Hossain, Syed Mozammel; Hussain, Md. Margub; Mostafa, Mohammad Golam; Laudico, Adriano V.; Siguan, Stephen Sixto S.; Adebamowo, Clement; Sun, Jing-zhong; Fei, Fei; Shao, Zhi-Ming; Yunjiang, Liu; Akram Hussain, Syed Md.; Zhang, Baoning; Lin, Cheng; Panigaro, Sonar; Walta, Fardiana; Chuan, Jiang Hong; Mirasol-Lumague, Maria Rica; Yip, Cheng-Har; Navarro, Narciso S.; Huang, Chiun-sheng; Lu, Yen-shen; Ferdousy, Tahmina; Salim, Reza; Akhter, Chameli; Nahar, Shamsun; Uy, Gemma; Young, Gregory S.; Hade, Erinn M.; Jarjoura, David

    2016-01-01

    Purpose In premenopausal women with metastatic hormone receptor positive breast cancer, hormonal therapy is the first line therapy. GnRH + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favorably influenced long-term outcomes. Methods 249 premenopausal women with incurable or metastatic hormone receptor positive breast cancer entered a trial in which they were randomized to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression free survival in the two randomized groups and by hormone confirmed menstrual cycle phase. Results Overall survival (OS) and progression-free survival were not demonstrated to be different in the two randomized groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels of <2ng/ml (anovulatory patients) (adjusted hazard ratio 1.46, 95% CI: 0.89–2.41, p=0.14) compared to patients in luteal phase with progesterone 2ng/ml or higher. Median overall survival was 2.0 years (95% CI: 1.7 – 2.3) and OS at 4 years was 26%. Conclusions The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT 00293540 PMID:27107325

  16. Luteal development and progesterone levels during pregnancy of the viviparous temperate lizard Barisia imbricata imbricata (Reptilia: Anguidae).

    PubMed

    Martínez-Torres, Martín; Elena Hernández-Caballero, Marta; Alvarez-Rodriguez, Carmen; Alba Luis-Díaz, Juana; Ortíz-López, Guadalupe

    2003-06-01

    The relationship between plasma progesterone (P(4)) levels and the formation and degeneration of the corpus luteum (CL) was assessed monthly during gestation of the viviparous lizard Barisia imbricata imbricata. Histochemical activity of the delta(5-4) isomerase 3 beta-hydroxysteroide dehydrogenase (delta(5-4)3beta-HSD) in the luteal tissue and embryonic development were also observed. Females were gravid throughout winter and great part of spring (late November or early December until late May or early June). Corpus luteum development occurred in the first third of gestation (December and January) when the embryo reached developmental stage 27. Four sequential stages were identified during development and three stages during regression of the CL. The follicular and thecal tissue participated in the formation of the luteal cell mass. According to Xavier's classification, the CL of B. i. imbricata is a subtype from Type III. The activity of delta(5-4)3beta-HSD was observed mainly in the luteal cell mass. The first degenerative changes in the CL were observed in the early second third of the gestation and continued gradually until parturition. Progesterone levels increased in early pregnancy and reached its highest level during January (3.07+/-1.04 ng/ml) when mature corpora lutea were present. Gradual diminution in progesterone concentrations occurred in the second and last third of pregnancy and coincided with advanced degenerative changes and diminution in histochemical activity of delta(5-4)3beta-HSD in the luteal tissue. These observations suggest that the CL is the major source of progesterone during pregnancy of B. i. imbricata.

  17. Androstenedione acts on the coeliac ganglion and modulates luteal function via the superior ovarian nerve in the postpartum rat.

    PubMed

    Vallcaneras, Sandra S; Casais, Marilina; Anzulovich, Ana C; Delgado, Silvia M; Sosa, Zulema; Telleria, Carlos M; Rastrilla, Ana M

    2011-07-01

    Androstenedione can affect luteal function via a neural pathway in the late pregnant rat. Here, we investigate whether androstenedione is capable of opposing to regression of pregnancy corpus luteum that occurs after parturition, indirectly, from the coeliac ganglion. Thus, androstenedione was added into the ganglionar compartment of an ex vivo coeliac ganglion-superior ovarian nerve-ovary system isolated from non-lactating rats on day 4 postpartum. At the end of incubation, we measured the abundance of progesterone, androstenedione and oestradiol released into the ovarian compartment. Luteal mRNA expression and activity of progesterone synthesis and degradation enzymes, 3β-hydroxysteroid-dehydrogenase (3β-HSD) and 20α-hydroxysteroid-dehydrogenase (20α-HSD), respectively, as well as the aromatase, Bcl-2, Bax, Fas and FasL transcript levels, were also determined. Additionally, we measured the ovarian release of norepinephrine, nitric oxide and luteal inducible nitric oxide synthase (iNOS) mRNA expression. The presence of androstenedione in the ganglion compartment significantly increased the release of ovarian progesterone, androstenedione and oestradiol without modifying 3β-HSD and 20α-HSD activities or mRNA expression. The ovarian release of oestradiol in response to the presence of androstenedione in the ganglion compartment declined with time of incubation in accord with a reduction in the aromatase mRNA expression. Androstenedione added to the ganglion compartment decreased FasL mRNA expression, without affecting luteal Bcl-2, Bax and Fas transcript levels; also increased the release of norepinephrine, decreased the release of nitric oxide and increased iNOS mRNA. In summary, on day 4 after parturition, androstenedione can mediate a luteotropic effect acting at the coeliac ganglion and transmitting to the ovary a signaling via a neural pathway in association with increased release of norepinephrine, decreased nitric oxide release, and decreased expression

  18. Time related changes in luteal prostaglandin synthesis and steroidogenic capacity during pregnancy, normal and antiprogestin induced luteolysis in the bitch.

    PubMed

    Kowalewski, Mariusz Pawel; Beceriklisoy, Hakki Bülent; Aslan, Selim; Agaoglu, Ali Reha; Hoffmann, Bernd

    2009-11-01

    In nonpregnant and pregnant dogs the corpora lutea (CL) are the only source of progesterone (P4) which shows an almost identical secretion pattern until the rapid decrease of P4 prior to parturition. For the nonpregnant dog clear evidence has been obtained that physiological luteal regression is devoid of a functional role of the PGF2alpha-system and seems to depend on the provision of StAR. Yet in pregnant dogs the rapid prepartal luteal regression, coinciding with an increase of PGF2alpha, may be indicative for different regulatory mechanisms. To assess this situation and by applying semi-quantitative Real Time (Taq Man) RT-PCR, expression patterns were determined for the following factors in CL of pregnant and prepartal dogs and of mid-pregnant dogs treated with the antiprogestin Aglepristone: cyclooxygenase 2 (Cox2), prostaglandin E2 synthase (PGES), prostaglandin F2alpha synthase (PGFS), its receptors (EP2, EP4 an FP), the steroidogenic acute regulatory protein (StAR), 3beta-hydroxysteroid-dehydrogenase (3betaHSD) and the progesterone receptor (PR). Peripheral plasma P4 concentrations were determined by RIA. CL were collected via ovariohysterectomy from pregnant bitches (n=3-5) on days 8-12 (Group 1, pre-implantation period), days 18-25 (Group 2, post-implantation period), days 35-40 (Group 3, mid-gestation period) and during the prepartal progesterone decline (Group 4). Additionally, CL were obtained from groups of 5 mid-pregnant dogs (days 40-45) 24h, respectively 72h after the second treatment with Aglepristone. Expression of Cox2 and PGES was highest during the pre-implantation period, that of PGFS and FP during the post-implantation period. EP4 and EP2 revealed a constant expression pattern throughout pregnancy with a prepartal upregulation of EP2. 3betaHSD and StAR decreased significantly from the pre-implatation period to prepartal luteolysis, it was matched by the course of P4 concentrations. Expression of the PR was higher during mid-gestation and

  19. Endocrine disruptors and human corpus luteum: in vitro effects of phenols on luteal cells function.

    PubMed

    Romani, Federica; Tropea, Anna; Scarinci, Elisa; Dello Russo, Cinzia; Lisi, Lucia; Catino, Stefania; Lanzone, Antonio; Apa, Rosanna

    2013-01-01

    Endocrine disruptors are well known to impair fertility. The aim of the present study was to investigate the effects of bisphenol A (BPA) and nonylphenol (p-NP) on human luteal function in vitro. In particular, in luteal cells isolated from 21 human corpora lutea progesterone, prostaglandin (PG) F2α, PGE2 and vascular endothelial growth factor (VEGF) release, as well as VEGF expression were evaluated. BPA and p-NP negatively affected both luteal steroidogenesis and luteotrophic/ luteolytic factors balance, without influencing VEGF mRNA expression. Actually, BPA and p-NP impaired human luteal cells function in vitro, underlining the already suggested correlation between phenols and reproductive failure.

  20. Follicular flushing in natural cycle IVF does not affect the luteal phase - a prospective controlled study.

    PubMed

    von Wolff, M; Kohl Schwartz, A; Stute, P; Fäh, M; Otti, G; Schürch, R; Rohner, S

    2017-07-01

    In contrast to multifollicular IVF, follicular flushing seems to increase the efficacy of monofollicular IVF treatments such as natural cycle IVF (NC-IVF). However, because follicular flushing causes loss of granulosa cells, it might negatively affect luteal phase length and endocrine function of the luteal body. A prospective cohort Phase II study was performed in 24 women undergoing NC-IVF. Women underwent a reference cycle with human chorionic gonadotrophin-induced ovulation without follicle aspiration and analysis of the length of the luteal phase and luteal concentrations of progesterone and oestradiol. In addition, they underwent a NC-IVF cycle which was performed identically but follicles were aspirated and flushed three times. The luteal phase was shorter in 29.2%, equal in 16.7% and longer in 50.0% of cases following flushing of the follicles. Overall, neither difference in luteal phase length was significant [median duration (interquartile range) in reference cycle: 13 (12; 14.5), IVF (flushing) cycle: 14 (12.5; 14.5), median difference (95% CI): 0.5 (-0.5 to 1.5)] nor median progesterone and oestradiol concentrations. In conclusion, follicular flushing in NC-IVF affects neither the length of the luteal phase nor the luteal phase concentrations of progesterone and oestradiol, questioning the need for luteal phase supplementation. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  1. Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus, pregnancy and normal and induced parturition

    PubMed Central

    2011-01-01

    Background Endocrine mechanisms governing canine reproductive function remain still obscure. Progesterone (P4) of luteal origin is required for maintenance of pregnancy. Corpora lutea (CL) are gonadotrop-independent during the first third of dioestrus; afterwards prolactin (PRL) is the primary luteotropic factor. Interestingly, the increasing PRL levels are accompanied by decreasing P4 concentrations, thus luteal regression/luteolysis occurs in spite of an increased availability of gonadotropic support. PRL acts through its receptor (PRLr), the expression of which has not yet been thoroughly investigated at the molecular and cellular level in the dog. Methods The expression of PRLr was assessed in CL of non-pregnant dogs during the course of dioestrus (days 5, 15, 25, 35, 45, 65 post ovulation; p.o.) as well as in CL, the utero/placental compartments (Ut/Pl) and interplacental free polar zones (interplacental sites) from pregnant dogs during the pre-implantation, post-implantation and mid-gestation period of pregnancy and during the normal and antigestagen-induced luteolysis. Expression of PRLr was tested by Real Time PCR, immunohistochemistry and in situ hybridization. Results In non-pregnant CL the PRLr expression was significantly upregulated at day 15 p.o. and decreased significantly afterwards, towards the end of dioestrus. CL of pregnancy showed elevated PRLr expression until mid gestation while prepartal downregulation was observed. Interestingly, placental but not interplacental expression of PRLr was strongly time-related; a significant upregulation was observed towards mid-gestation. Within the CL PRLr was localized to the luteal cells; in the Ut/Pl it was localized to the fetal trophoblast and epithelial cells of glandular chambers. Moreover, in mid-pregnant animals treated with an antigestagen, both the luteal and placental, but not the uterine PRLr were significantly downregulated. Conclusions The data presented suggest that the luteal provision of P4

  2. Anti-inflammatory effect of resveratrol on TNF-{alpha}-induced MCP-1 expression in adipocytes

    SciTech Connect

    Zhu Jian; Yong Wei; Wu Xiaohong; Yu Ying; Lv Jinghuan; Liu Cuiping; Mao Xiaodong; Zhu Yunxia; Xu Kuanfeng; Han Xiao Liu Chao

    2008-05-02

    Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-{alpha}-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-{alpha}-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-{alpha}-induced MCP-1 transcription. Nuclear factor (NF)-{kappa}B was determined to play a major role in the TNF-{alpha}-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-{kappa}B complex and subsequently suppressed NF-{kappa}B transcriptional activity in TNF-{alpha}-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies.

  3. Hypertonic saline attenuates TNF-alpha-induced NF-kappaB activation in pulmonary epithelial cells.

    PubMed

    Nydam, Trevor L; Moore, Ernest E; McIntyre, Robert C; Wright, Franklin L; Gamboni-Robertson, Fabia; Eckels, Phillip C; Banerjee, Anirban

    2009-05-01

    Resuscitation with hypertonic saline (HTS) attenuates acute lung injury (ALI) and modulates postinjury hyperinflammation. TNF-alpha-stimulated pulmonary epithelium is a major contributor to hemorrhage-induced ALI. We hypothesized that HTS would inhibit TNF-alpha-induced nuclear factor (NF)-kappaB proinflammatory signaling in pulmonary epithelial cells. Therefore, we pretreated human pulmonary epithelial cells (A549) with hypertonic medium (180 mM NaCl) for 30 min, followed by TNF-alpha stimulation (10 ng/mL). Key regulatory steps and protein concentrations in this pathway were assessed for significant alterations. Hypertonic saline significantly reduced TNF-alpha-induced intercellular adhesion molecule 1 levels and NF-kappaB nuclear localization. The mechanism is attenuated phosphorylation and delayed degradation of IkappaB alpha. Hypertonic saline did not alter TNF-alpha-induced p38 mitogen-activated protein kinase phosphorylation or constitutive vascular endothelial growth factor expression, suggesting that the observed inhibition is not a generalized suppression of protein phosphorylation or cellular function. These results show that HTS inhibits TNF-alpha-induced NF-kappaB activation in the pulmonary epithelium and, further, our understanding of its beneficial effects in hemorrhage-induced ALI.

  4. Analysis of recombinant human tumour necrosis factor-alpha-induced CD4 expression on human eosinophils.

    PubMed Central

    Hossain, M; Okubo, Y; Horie, S; Sekiguchi, M

    1996-01-01

    We examined the hypothesis that one of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression. Human eosinophils were cultured with various concentrations of recombinant human TNF-alpha (rhTNF-alpha) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil-derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross-linking of CD4 on eosinophils. The rhTNF-alpha induced CD4 expression on human eosinophils in a dose- and time-dependent fashion; rhTNF-alpha-induced CD4 expression was significantly inhibited by 10(-6) M cycloheximide, 10(-8) M dexamethasone, or 10(-6) M herbimycin A. Recombinant human interferon-gamma inhibited rhTNF-alpha-induced CD4 expression in a dose-dependent manner. However, cross-linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF-alpha-induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity. PMID:8690465

  5. The relationship between the production and the anti-gonadotrophic action of prostaglandin F 2 alpha in luteal cells from the marmoset monkey (Callithrix jacchus) in the early and mid-luteal phase.

    PubMed

    Webley, G E; Michael, A E; Abayasekara, D R E

    2010-04-01

    To address the potential luteolytic role for prostaglandin F(2 alpha) (PGF(2 alpha)) in the corpus luteum of the common marmoset monkey (Callithrix jacchus), the ability of marmoset luteal cells, maintained in monolayer culture, to produce PGF(2 alpha) was determined in vitro in the presence and absence of human chorionic gonadotrophin (hCG) and other established pharmacological modulators of PGF(2 alpha) synthesis. We also assessed the effects of the PGF(2 alpha) analogue, cloprostenol, on progesterone output from luteal cells isolated in the early luteal phase versus the mid-luteal phase (days 3 and 14 post ovulation, respectively). Cloprostenol had no effect on progesterone output from luteal cells isolated on day 3 of the luteal phase, whereas it significantly inhibited both basal and hCG-stimulated progesterone synthesis by day 14 luteal cells during the culture period 48-72 h (P<0.001). Intra-luteal PGF(2 alpha) concentrations were 5-fold higher in luteal cells isolated in the early luteal phase than in mid-luteal phase cells (16.5+/-3.5 versus 3.5+/-0.6 pmol/10(5) cells). While PGF(2 alpha) production was unaffected by hCG in vitro, it was decreased by indomethacin (1000 ng/ml) (P<0.05) and stimulated by the calcium ionophore A23187 (10 micromol/l) (P<0.05) in luteal cells from both stages of the luteal phase. Phospholipase A(2) did not influence PGF(2 alpha) production by day 3 luteal cells whereas at 10 IU/ml, it significantly stimulated PGF(2 alpha) production by day 14 luteal cells (P<0.05). Hence, the timing of luteolysis in the common marmoset monkey appears to involve changes in both the luteal cell response to and production of PGF(2 alpha).

  6. Receptors for gonadotrophin and prostaglandin F2 alpha in bovine corpora lutea of early, mid and late luteal phase.

    PubMed

    Rao, C V; Estergreen, V L; Carman, F R; Moss, G E

    1979-07-01

    A total of 15 corpora lutea representing early (day 3), mid (day 13) and late luteal phase (day 20 and 21-24) were obtained by ovariectomy on cycling cows. The luteal weights and peripheral plasma progesterone levels just prior to ovariectomy, were consistent with the above luteal phases. The specific binding of [125I]human chorionic gonadotrophin to membranes prepared from corpora lutea was significantly higher (P less than 0.01) for days 13 and 20 than for days 3 and 21-24. The binding in day 21-24 corpora lutea was higher (P less than 0.01) than day 3. Although there was no different either in number or affinity (apparent dissociation constant (Kd) = 0.04 nM) of gonadotrophin receptors in days 13 and 20 corpora lutea, only in the former did the binding correlate well with plasma progesterone levels. The specific binding of [3H]prostaglanding (PG)F2 alpha to the membranes of the same corpora lutea showed a progressive increase (P less than 0.01) from day 3, reached the highest value at a time when corpora lutea were actively regressing (day 20) and the decline (P less than 0.01) by day 21-24. Although a considerable number of PGF2 alpha receptors existed at day 13, the affinity of these same receptors was 203 times lower (Kd = 3458 nM) than the affinity of receptors in day 20 corpora lutea (Kd = 17 nM). In summary, the above results show that gonadotrophin receptors correlate with luteotrophic, whereas PGF2 alpha receptors correlate with luteolytic phases in bovine corpora lutea.

  7. Embryo transfer and luteal support in natural cycles.

    PubMed

    Vlaisavljevic, Veljko

    2007-06-01

    Embryo transfer policy and luteal supplementation was reviewed, comparing literature data and the results from the Maribor IVF Centre. A retrospective analysis of 1024 cycles in patients undergoing IVF, intracytoplasmic sperm injection (ICSI) or testicular sperm aspiration in unstimulated cycles was carried out using four different approaches for cycle monitoring. This showed that the most successful protocol for monitoring was administration of human chorionic gonadotrophin (HCG) when serum oestradiol was >0.49 nmol/l and follicle diameter was at least 15 mm. The implantation rate per transferred embryo was higher when a blastocyst was transferred (42.8%) rather than a day-2 embryo (23.5%) in the same monitoring protocol. Analysis of the influence of patient age on the success of oocyte retrieval, oocyte fertilization, embryo transfer rate and delivery rate demonstrates that patient age does not influence the rate of positive oocyte retrieval or fertilization rate as much as it influences pregnancy rate per embryo transfer. The delivery rate per cycle was dramatically influenced by age in patients over 38 years. There is no clear evidence in the literature as to whether luteal phase support is necessary in natural cycles for IVF/ICSI. Comparing the data, a higher pregnancy rate was observed if HCG was administered after embryo transfer.

  8. Arsenite enhances tumor necrosis factor-{alpha}-induced expression of vascular cell adhesion molecule-1

    SciTech Connect

    Tsou, T.-C. . E-mail: tctsou@nhri.org.tw; Yeh, Szu Ching; Tsai, E.-M.; Tsai, F.-Y.; Chao, H.-R.; Chang, Louis W.

    2005-11-15

    Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-{alpha} (TNF-{alpha}), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-{alpha}-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-{kappa}B (NF-{kappa}B). To elucidate the role of GSH in regulation of AP-1, NF-{kappa}B, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific {gamma}-glutamylcysteine synthetase ({gamma}-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-{alpha}-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-{kappa}B activations by TNF-{alpha}. Moreover, we found that depletion of GSH would also attenuate the TNF-{alpha}-induced VCAM-1 expression with a down-regulation of the TNF-{alpha}-induced NF-{kappa}B activation and without significant effect on AP-1. On the other hand, the TNF-{alpha}-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-{kappa}B activity, suggesting that activation of both AP-1 and NF-{kappa}B was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-{alpha}-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-{kappa}B activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions

  9. Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss

    PubMed Central

    Jukic, Anne Marie; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.

    2015-01-01

    Background Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. Objectives We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. Methods Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. Results Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: –0.5 days (95% CI: –0.9, –0.1), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: –0.8 days (95% CI: –1.2, –0.4), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.02), p = 0.001]. Conclusions BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle–specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies. Citation Jukic

  10. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    SciTech Connect

    Zhong, Xia; Li, Xiaonan; Liu, Fuli; Tan, Hui; Shang, Deya

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  11. Dehydrocostus lactone enhances tumor necrosis factor-alpha-induced apoptosis of human leukemia HL-60 cells.

    PubMed

    Oh, G S; Pae, H O; Chung, H T; Kwon, J W; Lee, J H; Kwon, T O; Kwon, S Y; Chon, B H; Yun, Young Gab

    2004-05-01

    Sesquiterpene lactones have raised considerable interest because of their ability to block the activation of nuclear transcription factor-kappaB (NF-kappaB). NF-kappaB plays an important role in the resistance of cancer cells to the induction of apoptosis by anticancer drugs and tumor necrosis factor-alpha (TNF-alpha). Pharmacological inhibition of NF-kappaB offers the promise of enhancing the efficacy of anticancer therapies. Here, we demonstrate that dehydrocostus lactone (DL), the major sesquiterpene lactone isolated from the roots of Saussurea lappa, inhibits NF-kappaB activation by preventing TNF-alpha-induced degradation and phosphorylation of its inhibitory protein I-kappaB alpha in human leukemia HL-60 cells and that DL renders HL-60 cells susceptible to TNF-alpha-induced apoptosis by enhancing caspase-8 and caspase-3 activities.

  12. Atropine, sodium cromoglycate, and thymoxamine in PGF2 alpha-induced bronchoconstriction in extrinsic asthma.

    PubMed Central

    Patel, K R

    1975-01-01

    In six patients with extrinsic bronchial asthma the inhalation of prostaglandin (PG) F2 alpha in a small dosage produced significant bronchoconstriction, whereas PGE2 produced bronchodilatation. In these patients cholinergic blockade with atropine partially inhibited the PGF2 alpha-induced bronchoconstriction, but the alpha-receptor-blocking drug thymoxamine and sodium cromoglycate did not. These results suggest that the effect of PGF2 alpha is mediated through cholinergic receptors in the airways, and this effect is grossly exaggerated in asthma. The failure to inhibit PGF2 alpha-induced bronchoconstriction with sodium cromoglycate and the observation of an inhibitory effect of sodium cromoglycate in both allergic and exercise asthma suggest that locally formed PGF2 alpha may not be the main factor in the pathogenesis of bronchial asthma. PMID:124195

  13. Transcriptome analysis reveals differences in mechanisms regulating cessation of luteal function in pregnant and non-pregnant dogs.

    PubMed

    Zatta, Sophie; Rehrauer, Hubert; Gram, Aykut; Boos, Alois; Kowalewski, Mariusz Pawel

    2017-09-27

    In the domestic dog, corpora lutea (CL) are the only source of progesterone (P4), both in pregnant and non-pregnant cycles because there is no placental steroidogenesis. The absence of an endogenous luteolysin in absence of pregnancy results in long-lasting physiological pseudopregnancy, strongly contrasting with the acute luteolysis observed prepartum. The underlying biological mechanisms and the involvement of P4 signalling remain, however, not fully understood. Therefore, here, next-generation sequencing (RNA-Seq) was performed on CL from the late luteal phase and compared with normally luteolyzing CL collected at the prepartum P4 decrease. The contrast "luteal regression over luteolysis" yielded 1595 differentially expressed genes (DEG). The CL in late luteal regression were predominantly associated with functional terms linked to extracellular matrix (p = 5.52e-05). Other terms related to transcriptional activity (p = 2.45e-04), and steroid hormone signalling (p = 2.29e-04), which were more highly represented in late regression than during luteolysis. The prepartum luteolysis was associated with immune inflammatory responses (p = 2.87e-14), including acute-phase reaction (p = 4.10e-06). Immune system-related events were also more highly represented in CL derived from normal luteolysis (p = 7.02e-04), compared with those from dogs in which luteolysis was induced with an antigestagen (1480 DEG in total). Additionally, the withdrawal of P4 at mid-gestation resulted in 92 DEG; over-represented terms enriched in antigestagen-treated dogs were related to the inflammatory response (p = 0.005) or response to IL1 (p = 7.29e-05). Terms related to proliferation, e.g., centrosome organization (p = 0.002) and steroid metabolic processes (p = 0.001), prevailed at mid-gestation. Thereby, our results revealed the nature of luteotropic effects of P4 within canine CL. It appears that, even though they result in diminished steroidogenic output, the effect of

  14. The role of adrenergic activation on murine luteal cell viability and progesterone production.

    PubMed

    Wang, Jing; Tang, Min; Jiang, Huaide; Wu, Bing; Cai, Wei; Hu, Chuan; Bao, Riqiang; Dong, Qiming; Xiao, Li; Li, Gang; Zhang, Chunping

    2016-09-15

    Sympathetic innervations exist in mammalian CL. The action of catecholaminergic system on luteal cells has been the focus of a variety of studies. Norepinephrine (NE) increased progesterone secretion of cattle luteal cells by activating β-adrenoceptors. In this study, murine luteal cells were treated with NE and isoprenaline (ISO). We found that NE increased the viability of murine luteal cells and ISO decreased the viability of luteal cells. Both NE and ISO promoted the progesterone production. Nonselective β-adrenergic antagonist, propranolol reversed the effect of ISO on cell viability but did not reverse the effect of NE on cell viability. Propranolol blocked the influence of NE and ISO on progesterone production. These results reveal that the increase of luteal cell viability induced by NE is not dependent on β-adrenergic activation. α-Adrenergic activation possibly contributes to it. Both NE and ISO increased progesterone production through activating β-adrenergic receptor. Further study showed that CyclinD2 is involved in the increase of luteal cell induced by NE. 3β-Hydroxysteroid dehydrogenase, LHR, steroidogenic acute regulatory protein (StAR), and PGF2α contribute to the progesterone production induced by NE and ISO. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Luteal phase support for assisted reproductive technologies: between past, present and future.

    PubMed

    Lo Monte, G; Piva, I; Bazzan, E; Marci, R; Ogrin, C

    2013-12-01

    The luteal phase is defined as the period between ovulation and either the establishment of a pregnancy or the onset of menses two weeks later. Assisted reproductive technologies (ART), and in particular controlled ovarian stimulation (COS), negatively interfere with the endocrine mechanisms normally regulating the luteal phase. Up to now, there is no generally accepted opinion as to the most appropriate therapeutic schemes for luteal phase support in ART cycles. Progesterone-based protocols are the most frequently adopted, while alternative regimens including human chorionic gonadotropin (hCG) and GnRH agonists (GnRH-a) are controversial. A GnRH-a can be used instead of hCG for ovulation triggering and the effectiveness of luteal phase support in such new protocols is the object of a growing number of experimental studies. Currently, vaginal progesterone is considered as the first line therapy for luteal phase support (LPS). The starting-time and the duration of luteal phase supplementation after the onset of pregnancy are still debated. Despite the lack of clinical or biological evidence supporting the efficacy of luteal phase support in intrauterine insemination cycles, the use of progesterone has become a well-established practice.

  16. Characterization of hormonal profiles during the luteal phase in regularly menstruating women.

    PubMed

    Ecochard, Rene; Bouchard, Thomas; Leiva, Rene; Abdulla, Saman; Dupuis, Olivier; Duterque, Olivia; Garmier Billard, Marie; Boehringer, Hans; Genolini, Christophe

    2017-07-01

    To characterize the variability of hormonal profiles during the luteal phase in normal cycles. Observational study. Not applicable. Ninety-nine women contributing 266 menstrual cycles. The women collected first morning urine samples that were analyzed for estrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FSH, and LH. The women had serum P tests (twice per cycle) and underwent ultrasonography to identify the day of ovulation. The luteal phase was divided into three parts: the early luteal phase with increasing PDG (luteinization), the midluteal phase with PDG ≥10 μg/mg Cr (progestation), and the late luteal phase (luteolysis) when PDG fell below 10 μg/mg Cr. Long luteal phases begin with long luteinization processes. The early luteal phase is marked by low PDG and high LH levels. Long luteinization phases were correlated with low E1G and low PDG levels at day 3. The length of the early luteal phase is highly variable between cycles of the same woman. The duration and hormonal levels during the rest of the luteal phase were less correlated with other characteristics of the cycle. The study showed the presence of a prolonged pituitary activity during the luteinization process, which seems to be modulated by an interaction between P and LH. This supports a luteal phase model with three distinct processes: the first is a modulated luteinization process, whereas the second and the third are relatively less modulated processes of progestation and luteolysis. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Glutathione regulation of redox-sensitive signals in tumor necrosis factor-alpha-induced vascular endothelial dysfunction.

    PubMed

    Tsou, Tsui-Chun; Yeh, Szu Ching; Tsai, Feng-Yuan; Chen, Jein-Wen; Chiang, Huai-Chih

    2007-06-01

    We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-alpha)-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-alpha induces various biological effects on vascular cells, TNF-alpha dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-alpha concentrations, we adopted the lower TNF-alpha (0.2 ng/ml) to rule out the possible involvement of other TNF-alpha-induced biological effects. Inhibition of glutathione synthesis by l-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-alpha-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-alpha-induced nuclear factor-kappaB (NF-kappaB) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-alpha. Inhibition of ERK, JNK, or NF-kappaB attenuates TNF-alpha-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-alpha induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-kappaB in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-alpha. Although AP-1 activation by the lower TNF-alpha was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-alpha-induced adhesion molecule expression.

  18. Glutathione regulation of redox-sensitive signals in tumor necrosis factor-{alpha}-induced vascular endothelial dysfunction

    SciTech Connect

    Tsou, T.-C. . E-mail: tctsou@nhri.org.tw; Yeh, S.C.; Tsai, F.-Y.; Chen, J.-W.; Chiang, H.-C.

    2007-06-01

    We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-{alpha})-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-{alpha} induces various biological effects on vascular cells, TNF-{alpha} dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-{alpha} concentrations, we adopted the lower TNF-{alpha} (0.2 ng/ml) to rule out the possible involvement of other TNF-{alpha}-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-{alpha}-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-{alpha}-induced nuclear factor-kappaB (NF-{kappa}B) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-{alpha}. Inhibition of ERK, JNK, or NF-{kappa}B attenuates TNF-{alpha}-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-{alpha} induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-{kappa}B in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-{alpha}. Although AP-1 activation by the lower TNF-{alpha} was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-{alpha}-induced adhesion molecule expression.

  19. Evaluation of models to induce low progesterone during the early luteal phase in cattle.

    PubMed

    Beltman, M E; Roche, J F; Lonergan, P; Forde, N; Crowe, M A

    2009-10-15

    Two experiments were designed to evaluate models for generation of low circulating progesterone concentrations during early pregnancy in cattle. In Experiment 1, 17 crossbred heifers (Bos taurus) were assigned to either prostaglandin F(2alpha) (PGF(2alpha)) administration on Days 3, 3.5, and 4 (PG3; n=9) or to control (n=8). Blood samples were collected from heifers from Days 1 to 9 for progesterone assay. Progesterone concentrations were decreased (P<0.03) between 18 and 48h after first PGF(2alpha) treatment in heifers assigned to PG3 compared with that of controls. In Experiment 2, 39 crossbred heifers detected in estrus were inseminated (Day 0) and assigned to either (1) PGF(2alpha) administration on Days 3, 3.5, and 4 (PG3; n=10), (2) PGF(2alpha) administration on Days 3, 3.5, 4, and 4.5 (PG4; n=10), (3) Progesterone Releasing Intravaginal Device (PRID) insertion on Day 4.5 with PGF(2alpha) administration on Days 5 and 6 (PRID+PGF(2alpha); n=10), or (4) control (n=9). Blood samples were collected daily until Day 15, and conceptus survival rate was determined at slaughter on Day 16. Progesterone concentrations during the sampling period in the PG3 and PG4 groups did not differ but were less than that of controls (P<0.01). After an initial peak, progesterone concentrations in the PRID+PGF(2alpha) group were similar to that of controls. More heifers in the PG4 group (6 of 10) had complete luteal regression than did those in the PG3 group (3 of 10). Conceptus survival rate on Day 16 did not differ between groups. There was a significant correlation between progesterone concentration on Days 5 and 6 and conceptus size on Day 16. In summary, treatment with PGF(2alpha) on Days 3, 3.5, and 4 postestrus appeared to provide the best model to induce reduced circulating progesterone concentrations during the early luteal phase in cattle.

  20. Prostaglandin F2 alpha stimulates progesterone secretion by porcine luteal cells in vitro throughout the estrous cycle.

    PubMed

    Gadsby, J E; Earnest, K L

    1994-08-01

    In this study we examined the stimulatory effects of PGF2 alpha on progesterone secretion by porcine luteal cells on different days of the estrous cycle, and the effects of PGF2 alpha, A23187 and PMA on progesterone secretion by isolated large and small luteal cells, in vitro. Corpora lutea were obtained from cycling pigs (days 6-16), collagenase dispersed and luteal cells incubated in medium 199 in the absence or presence of increasing doses of PGF2 alpha, A23187, and PMA. Progesterone concentrations in spent media were measured by RIA. PGF2 alpha stimulation of progesterone secretion by mixed luteal cells did not vary significantly throughout the estrous cycle. Progesterone secretion by large, but not small, luteal cells was increased (p < 0.05) in a dose-dependent fashion by PGF2 alpha. A23187 also caused a dose-dependent increase in progesterone secretion by large luteal cells but inhibited small luteal cells. Progesterone secretion by both large and small luteal cells was significantly increased by increasing doses of PMA. We conclude that the stimulatory response of luteal cells to PGF2 alpha in vitro did not correlate with PGF2 alpha receptor concentrations (not measured in this study), and we speculate that calcium/protein kinase C may be involved in mediating the stimulatory action of PGF2 alpha on luteal cell progesterone secretion.

  1. Estrogen Promotes Luteolysis by Redistributing Prostaglandin F2α Receptors Within Primate Luteal Cells*

    PubMed Central

    Kim, Soon Ok; Markosyan, Nune; Pepe, Gerald J.; Duffy, Diane M.

    2015-01-01

    Prostaglandin F2α (PGF2α) has been proposed as a functional luteolysin in primates. However, administration of PGF2α or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2α receptors (PTGFR) or responsiveness to PGF2α at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized to the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production by luteal cells obtained at mid-late and late luteal phases but did not decrease progesterone production by granulosa or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates. PMID:25687410

  2. Effects of beta-carotene and vitamin A on bovine luteal function

    SciTech Connect

    Graves-Hoagland, R.L.

    1987-01-01

    Initially, the direct effects of B-carotene and vitamin A on progesterone (P4) production were studied by exposing dispersed luteal cells to these compounds in vitro. There were no positive relationships between P4 and B-carotene or vitamin A. However, a negative, and perhaps toxic, effect of a large dose of B-carotene on P4 reproduction was noted. A positive relationship between plasma B-carotene and percent change of P4 in the medium of dispersed luteal cells was demonstrated when these plasma metabolites were measured in slaughterhouse cows from which CL were obtained for incubation. This relationship was only present during the winter when plasma levels of B-carotene and vitamin A were considerably lower. Preliminary investigations into the mechanism of action of B-carotene and/or vitamin A were initiated. Luteal tissue ribonucleic acid (RNA), deoxyribonucleic acid (DNA), the RNA to DNA ratio and total protein concentration were measured to study the influence of plasma levels of B-carotene and vitamin A on the protein synthetic capacity of luteal tissue. There were no relationships detected, however, RNA concentration and the RNA to DNA ratio of luteal tissue were greater during the summer. The percent binding of radiolabeled vitamin A was greater in the nuclear than in the cytoplasmic component of the luteal cell.

  3. A simple and economical method in purifying dairy goat luteal cells.

    PubMed

    Wang, Zhonghui; Chen, Shulin; Mo, Hongfei; Huang, Yingxue; Li, Jinyan; Sun, Jianbo; Liu, Lei; Zhao, Shantin

    2013-08-01

    As an important cell model, luteal cells are used to study the reproductive cycle and pregnancy maintenance, but there has not yet had a simple and economical method in purifing goat luteal cells. In order to find a good method to isolate and purify the luteal cells from the Guan Zhong dairy goat corpus luteua, we compared the purification efficiency of Percoll density gradient centrifugation method with that of the differential detachment method using trypsin. After using these two methods for isolation, the purified cells were identified by staining for 3β-hydroxy steroid dehydrogenase activity. Cell diameter measurements and cell counting were used to categorize isolated cells from both methods. Cell proliferation activity of purified cells from both methods were studied by Cell Counting Kit-8 for 8 days. The results showed that, after Percoll discontinuous density gradient centrifugation, the purity of luteal cells was 98.2±1.2% in Percoll density layer of 30-40%. In comparison, the purity of luteal cells isolated in differential detachment by trypsin was 74.3±1.8%. Luteal cells purified from both methods stained positive for 3β-hydroxy steroid dehydrogenase activity, and cells purified by Percoll centrifugation showed a more rapid cell proliferation rate than cells purified by trypsin. In conclusion, this study has demonstrated that Percoll density gradient centrifugation was superior to the method of differential detachment in cell purification efficiency and in maintenance of cell proliferation activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Assessment of progesterone profiles and postpartum onset of luteal activity in spring calving Hereford beef suckler cattle

    PubMed Central

    2010-01-01

    Background Reproduction is the single greatest factor limiting beef cattle production. Previous research on beef suckler luteal activity has largely focused on the mechanisms, and duration, of postpartum anoestrus. However, the temporal pattern of luteal activity after resumption of post-partum ovarian activity, and the impact of pattern type on days open (DO) in purebred beef suckler cows, are unknown. Methods Progesterone concentration was measured in milk samples taken thrice weekly from 120 lactations, in 87 animals, on 3 farms, over two years. Onset of luteal activity (OLA) was defined as the first day milk progesterone concentration exceeded 3 ng/ml for two successive measurements, or exceeded 5 ng/ml once. It was defined as delayed if it occurred more than 61 days postpartum. A short initial luteal phase consisted of progesterone concentrations which exceeded 3 ng/ml for fewer than 4 sequential measurements. Temporal progesterone patterns were classified as: 1) Normal cyclicity; 2) Cessation of luteal activity; 3) Prolonged luteal activity; 4) Erratic phase: failure to conform to 1, 2 or 3. Data concerning parity, previous calving interval, breeding values, calf birth and 200-d weight were obtained from the Norwegian Beef Cattle Recording System database. Results The mean (SD) OLA was 41 d (20). Parity and calf birth weight were inversely correlated with OLA. Delayed OLA occurred in 14.4% of lactations. A short first luteal phase occurred in 61.5% of lactations, but this was unrelated to irregular luteal phase occurrence, pregnancy or DO. Irregular luteal phases occurred in 22% of lactations. The irregularities were: prolonged luteal phase (11%); cessation of luteal activity (5%); erratic luteal activity (6%). Early OLA was associated with prolonged luteal phases. DO was positively correlated with irregular luteal phases and negatively correlated with calf 200-d weight. Conclusions This study demonstrates that irregular luteal phases negatively affect

  5. Assessment of progesterone profiles and postpartum onset of luteal activity in spring calving Hereford beef suckler cattle.

    PubMed

    Martin, Adam D; Lystad, Marit L; Reksen, Olav; Ropstad, Erik; Waldmann, Andres; Nafstad, Ola; Karlberg, Knut

    2010-06-15

    Reproduction is the single greatest factor limiting beef cattle production. Previous research on beef suckler luteal activity has largely focused on the mechanisms, and duration, of postpartum anoestrus. However, the temporal pattern of luteal activity after resumption of post-partum ovarian activity, and the impact of pattern type on days open (DO) in purebred beef suckler cows, are unknown. Progesterone concentration was measured in milk samples taken thrice weekly from 120 lactations, in 87 animals, on 3 farms, over two years. Onset of luteal activity (OLA) was defined as the first day milk progesterone concentration exceeded 3 ng/ml for two successive measurements, or exceeded 5 ng/ml once. It was defined as delayed if it occurred more than 61 days postpartum. A short initial luteal phase consisted of progesterone concentrations which exceeded 3 ng/ml for fewer than 4 sequential measurements. Temporal progesterone patterns were classified as: 1) Normal cyclicity; 2) Cessation of luteal activity; 3) Prolonged luteal activity; 4) Erratic phase: failure to conform to 1, 2 or 3. Data concerning parity, previous calving interval, breeding values, calf birth and 200-d weight were obtained from the Norwegian Beef Cattle Recording System database. The mean (SD) OLA was 41 d (20). Parity and calf birth weight were inversely correlated with OLA. Delayed OLA occurred in 14.4% of lactations. A short first luteal phase occurred in 61.5% of lactations, but this was unrelated to irregular luteal phase occurrence, pregnancy or DO. Irregular luteal phases occurred in 22% of lactations. The irregularities were: prolonged luteal phase (11%); cessation of luteal activity (5%); erratic luteal activity (6%). Early OLA was associated with prolonged luteal phases. DO was positively correlated with irregular luteal phases and negatively correlated with calf 200-d weight. This study demonstrates that irregular luteal phases negatively affect reproductive performance in purebred beef

  6. Subfertility linked to combined luteal insufficiency and uterine progesterone resistance.

    PubMed

    Konno, Toshihiro; Graham, Amanda R; Rempel, Lea A; Ho-Chen, Jennifer K; Alam, S M Khorshed; Bu, Pengli; Rumi, M A Karim; Soares, Michael J

    2010-09-01

    Early pregnancy loss is common and can be caused by a range of factors. The Brown Norway (BN) rat exhibits reproductive dysfunction characterized by small litter size and pregnancy failure and represents a model for investigating early pregnancy loss. In this study, we investigated the establishment of pregnancy in the BN rat and gained insight into mechanisms causing its subfertility. Early stages of BN uteroplacental organization are unique. The BN primordial placenta is restricted in its development and correlates with limited BN uterine decidual development. BN uterine decidua was shown to be both structurally and functionally distinct and correlated with decreased circulating progesterone (P4) levels. Ovarian anomalies were also apparent in BN rats and included decreased ovulation rates and decreased transcript levels for some steroidogenic enzymes. Attempts to rescue the BN uterine decidual phenotype with steroid hormone therapy were ineffective. BN uteri were shown to exhibit reduced responsiveness to P4 but not to 17beta-estradiol. P4 resistance was associated with decreased transcript levels for the P4 receptor (Pgr), a P4 receptor chaperone (Fkbp4), and P4 receptor coactivators (Ncoa1 and Ncoa2). In summary, the BN rat exhibits luteal insufficiency and uterine P4 resistance, which profoundly affects its ability to reproduce.

  7. The HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis

    SciTech Connect

    Wang, Yisong

    2005-10-01

    Interferons (IFNs) exert antitumor effects in several human malignancies, but their mechanism of action is unclear. There is a great variability in sensitivity to IFN treatment depending on both tumor type and the individual patient. The reason for this variable sensitivity is not known. The fact that several IFN-induced anticellular effects are exerted through modulation of proto-oncogenes and tumor suppressor genes may indicate that the malignant genotype may be decisive in the cell's sensitivity to IFN. To determine if a deregulated oncogene could alter the cellular response to IFN, a mouse lymphoma cell line (J3D) was stably transfected with the viral human papillomavirus-16 (HPV-16) E7 oncogene. The E7-transfected cells and their respective mock-transfected sister clones were treated with IFN-{alpha} and examined for possible IFN-induced anticellular effects. We found that the E7-transfected clones were greatly sensitized to IFN-{alpha}-induced apoptosis compared with their mock-transfected counterparts. Induction of apoptosis in the transfected cells correlated with the ability of IFN to activate parts of the proapoptotic machinery specifically in these cells, including activation of caspases and the proapoptotic protein Bak. In summary, our data suggest that transfection of malignant cells with the E7 oncogene can sensitize them to IFN-{alpha}-induced apoptosis. This demonstrates that an oncogenic event may alter the cellular sensitivity to IFN and might also have implications for treatment of HPV related diseases with IFN.

  8. Role of nitric oxide in PGF2 alpha-induced ocular hyperemia.

    PubMed

    Astin, M; Stjernschantz, J; Selén, G

    1994-10-01

    The effect of nitric oxide synthase inhibition on prostaglandin F2 alpha (PGF2 alpha)-induced ocular hyperemia in the rabbit has been studied. PGF2 alpha was administered topically as the isopropyl ester (PGF2 alpha-IE) unilaterally, with the other eye serving as a control. The regional blood flow in the eye was determined with radioactively-labelled microspheres in conscious animals. Synthesis of nitric oxide (NO) was blocked by L-NMMA (200 mg kg-1 b.w., i.v.). PGF2 alpha-IE induced marked hyperemia of the surface structures of the eye (conjunctiva, eye lids, nictitating membrane, anterior sclera), as well as increased blood flow of the anterior uvea. L-NMMA blocked the hyperemia of the surface structures but not completely the increase in blood flow of the anterior uvea. PhXA41 (13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2 alpha-isopropyl ester), a selective prostaglandin FP-receptor agonist, had no significant effect on the ocular blood flow. These results indicate that PGF2 alpha causes surface hyperemia of the eye by activating nitric oxide synthase, but this mechanism seems to be only partly involved in the increase in blood flow of the ciliary processes and the iris. The PGF2 alpha-induced ocular hyperemia is unlikely to be mediated by FP receptors.

  9. The {alpha}-induced thick-target {gamma}-ray yield from light elements

    SciTech Connect

    Heaton, R.K. |

    1994-10-01

    The {alpha}-induced thick-target {gamma}-ray yield from light elements has been measured in the energy range 5.6 MeV {le} E{sub {alpha}} {le} 10 MeV. The {gamma}-ray yield for > 2.1 MeV from thick targets of beryllium, boron nitride, sodium fluoride, magnesium, aluminum and silicon were measured using the {alpha}-particle beam from the Lawrence Berkeley Laboratories 88 in. cyclotron. The elemental yields from this experiment were used to construct the {alpha}-induced direct production {gamma}-ray spectrum from materials in the SNO detector, a large volume ultra-low background neutrino detector located in the Creighton mine near Sudbury, Canada. This background source was an order of magnitude lower than predicted by previous calculations. These measurements are in good agreement with theoretical calculations of this spectrum based on a statistical nuclear model of the reaction, with the gross high energy spectrum structure being reproduced to within a factor of two. Detailed comparison of experimental and theoretical excitation population distribution of several residual nuclei indicate the same level of agreement within experimental uncertainties.

  10. Influence of omega-3 fatty acids on bovine luteal cell plasma membrane dynamics.

    PubMed

    Plewes, Michele R; Burns, Patrick D; Hyslop, Richard M; George Barisas, B

    2017-09-11

    Fish oil is a rich source of omega-3 fatty acids which disrupt lipid microdomain structure and affect mobility of the prostaglandin F2α (FP) receptor in bovine luteal cells. The objectives of this study were to determine the effects of individual omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on 1) membrane fatty acid composition, 2) lipid microdomain structure, and 3) lateral mobility of the FP receptor in bovine luteal cells. Ovaries were collected from a local abattoir (n=5/experiment). The corpus luteum was resected and enzymatically digested using collagenase to generate a mixed luteal cell population. In all experiments, luteal cells were treated with 0, 1, 10 or 100μM EPA or DHA for 72h to allow incorporation of fatty acids into membrane lipids. Results from experiment 1 show that culturing luteal cells in the presence of EPA or DHA increased these luteal fatty acids. In experiment 2, both EPA and DHA increased spatial distribution of lipid microdomains in a dose-dependent manner. Single particle tracking results from experiment 3 show that increasing both EPA and DHA concentrations increased micro- and macro-diffusion coefficients, increased domain size, and decreased residence time of FP receptors. Collectively, results from this study demonstrate similar effects of EPA and DHA on lipid microdomain structure and lateral mobility of FP receptors in cultured bovine luteal cells. Moreover, only 10μM of either fatty acid was needed to mimic the effects of fish oil. Copyright © 2017. Published by Elsevier B.V.

  11. Eicosapentaenoic acid inhibits TNF-{alpha}-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells

    SciTech Connect

    Kim, Hyeon Ho; Lee, Youngae; Eun, Hee Chul Chung, Jin Ho

    2008-04-04

    Eicosapentaenoic acid (EPA) is an omega-3 ({omega}-3) polyunsaturated fatty acid (PUFA), which has anti-inflammatory and anti-cancer properties. Some reports have demonstrated that EPA inhibits NF-{kappa}B activation induced by tumor necrosis factor (TNF)-{alpha} or lipopolysaccharide (LPS) in various cells. However, its detailed mode of action is unclear. In this report, we investigated whether EPA inhibits the expression of TNF-{alpha}-induced matrix metalloproteinases (MMP)-9 in human immortalized keratinocytes (HaCaT). TNF-{alpha} induced MMP-9 expression by NF-{kappa}B-dependent pathway. Pretreatment of EPA inhibited TNF-{alpha}-induced MMP-9 expression and p65 phosphorylation. However, EPA could not affect I{kappa}B-{alpha} phosphorylation, nuclear translocation of p65, and DNA binding activity of NF-{kappa}B. EPA inhibited TNF-{alpha}-induced p65 phosphorylation through p38 and Akt inhibition and this inhibition was IKK{alpha}-dependent event. Taken together, we demonstrate that EPA inhibits TNF-{alpha}-induced MMP-9 expression through inhibition of p38 and Akt activation.

  12. The coffee diterpene kahweol inhibits tumor necrosis factor-{alpha}-induced expression of cell adhesion molecules in human endothelial cells

    SciTech Connect

    Kim, Hyung Gyun; Kim, Ji Young; Hwang, Yong Pil; Lee, Kyung Jin; Lee, Kwang Youl; Kim, Dong Hee; Kim, Dong Hyun; Jeong, Hye Gwang . E-mail: hgjeong@chosun.ac.kr

    2006-12-15

    Endothelial cells produce adhesion molecules after being stimulated with various inflammatory cytokines. These adhesion molecules play an important role in the development of atherogenesis. Recent studies have highlighted the chemoprotective and anti-inflammatory effects of kahweol, a coffee-specific diterpene. This study examined the effects of kahweol on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. Kahweol inhibited the adhesion of TNF{alpha}-induced monocytes to endothelial cells and suppressed the TNF{alpha}-induced protein and mRNA expression of the cell adhesion molecules, VCAM-1 and ICAM-1. Furthermore, kahweol inhibited the TNF{alpha}-induced JAK2-PI3K/Akt-NF-{kappa}B activation pathway in these cells. Overall, kahweol has anti-inflammatory and anti-atherosclerotic activities, which occurs partly by down-regulating the pathway that affects the expression and interaction of the cell adhesion molecules on endothelial cells.

  13. Mid-luteal estradiol levels of poor/good responders and intracytoplasmic sperm injection

    PubMed Central

    Rehman, Rehana; Tariq, Sundus; Tariq, Saba; Hashmi, Faisal; Baig, Mukhtiar

    2017-01-01

    Objective: To assess mid-luteal estradiol (E2) levels in poor and good responders and determine its effect on the outcome after intracytoplasmic sperm injection (ICSI). Methods: The current study was carried out in females who underwent ICSI from June 2011 to September 2013 in “Islamabad Clinic Serving Infertile Couples”. They were categorized into good and poor responders on the basis of female age ≤40 years, basal follicle stimulating hormone ≤12 mIU/ml, and antral follicle count >5, respectively. Their mid-luteal E2 measured on the day of embryo transfer was stratified into groups (A-E) on the basis of 20th, 40th, 60th and 80th percentile values. The outcome was categorized into non-pregnant with beta human chorionic Gonadotrophin (hCG) 5-25 m IU/ml, and clinical pregnancy with beta hCG>25 m IU/ml. Results: The conception rate was 12% (63/513) in poor responders and 72% (237/329) in good responders respectively. The mid-luteal E2 levels were higher in conception as compared to non-conception cycles (p<0.001) in good and poor responders. Conclusion: Maximum pregnancies in poor and good responders (53% and 98% respectively) with mid-luteal E2 levels above 80th percentiles confirm the role of the increase in mid-luteal E2 for augmentation in conception rate of females after ICSI. PMID:28367196

  14. Prostaglandin F2 alpha synthesis and metabolism by luteal phase endometrium in vitro.

    PubMed

    Brumsted, J R; Chapitis, J; Deaton, J L; Riddick, D H; Gibson, M

    1989-11-01

    Differences in prostaglandin (PG) F2 alpha synthesis and degradation were sought between early luteal endometrium (histology day 15 to 22, n = 6) and late luteal endometrium (histology day 23 to 28, n = 6). In addition, alterations in PGF2 alpha synthesis and degradation in response to 17 beta-estradiol (E2) and progesterone (P) were examined to clarify the mechanism of steroid modulation of endometrial PG production (n = 12). Endometrium was maintained in tissue culture and the concentration of PGF2 alpha and 13,14 dehydro-15 keto F2 alpha (DHKF2 alpha) was determined in spent media by radioimmunoassay. Prostaglandin F2 alpha and DHKF2 alpha output from luteal endometrium exposed to P and E2 + P were both significantly reduced when compared with no addition or E2 treatments. This implies that the modulation of PGF2 alpha output by P in vitro is secondary to altered synthesis. There was an increase in PGF2 alpha output from late luteal endometrium when compared with early luteal endometrium in the P and E2 + P treatments, but DHKF2 alpha remained unchanged. These data imply that the temporal increase in PGF2 alpha output is the result of alterations in both PG synthesis and catabolism.

  15. Clinostat rotation induces apoptosis in luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Yang, Hyunwon; Bhat, Ganapathy K.; Sridaran, Rajagopala

    2002-01-01

    Recent studies have shown that microgravity induces changes at the cellular level, including apoptosis. However, it is unknown whether microgravity affects luteal cell function. This study was performed to assess whether microgravity conditions generated by clinostat rotation induce apoptosis and affect steroidogenesis by luteal cells. Luteal cells isolated from the corpora lutea of Day 8 pregnant rats were placed in equal numbers in slide flasks (chamber slides). One slide flask was placed in the clinostat and the other served as a stationary control. At 48 h in the clinostat, whereas the levels of progesterone and total cellular protein decreased, the number of shrunken cells increased. To determine whether apoptosis occurred in shrunken cells, Comet and TUNEL assays were performed. At 48 h, the percentage of apoptotic cells in the clinostat increased compared with that in the control. To investigate how the microgravity conditions induce apoptosis, the active mitochondria in luteal cells were detected with JC-1 dye. Cells in the control consisted of many active mitochondria, which were evenly distributed throughout the cell. In contrast, cells in the clinostat displayed fewer active mitochondria, which were distributed either to the outer edge of the cell or around the nucleus. These results suggest that mitochondrial dysfunction induced by clinostat rotation could lead to apoptosis in luteal cells and suppression of progesterone production.

  16. Clinostat rotation induces apoptosis in luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Yang, Hyunwon; Bhat, Ganapathy K.; Sridaran, Rajagopala

    2002-01-01

    Recent studies have shown that microgravity induces changes at the cellular level, including apoptosis. However, it is unknown whether microgravity affects luteal cell function. This study was performed to assess whether microgravity conditions generated by clinostat rotation induce apoptosis and affect steroidogenesis by luteal cells. Luteal cells isolated from the corpora lutea of Day 8 pregnant rats were placed in equal numbers in slide flasks (chamber slides). One slide flask was placed in the clinostat and the other served as a stationary control. At 48 h in the clinostat, whereas the levels of progesterone and total cellular protein decreased, the number of shrunken cells increased. To determine whether apoptosis occurred in shrunken cells, Comet and TUNEL assays were performed. At 48 h, the percentage of apoptotic cells in the clinostat increased compared with that in the control. To investigate how the microgravity conditions induce apoptosis, the active mitochondria in luteal cells were detected with JC-1 dye. Cells in the control consisted of many active mitochondria, which were evenly distributed throughout the cell. In contrast, cells in the clinostat displayed fewer active mitochondria, which were distributed either to the outer edge of the cell or around the nucleus. These results suggest that mitochondrial dysfunction induced by clinostat rotation could lead to apoptosis in luteal cells and suppression of progesterone production.

  17. Clinostat rotation induces apoptosis in luteal cells of the pregnant rat.

    PubMed

    Yang, Hyunwon; Bhat, Ganapathy K; Sridaran, Rajagopala

    2002-03-01

    Recent studies have shown that microgravity induces changes at the cellular level, including apoptosis. However, it is unknown whether microgravity affects luteal cell function. This study was performed to assess whether microgravity conditions generated by clinostat rotation induce apoptosis and affect steroidogenesis by luteal cells. Luteal cells isolated from the corpora lutea of Day 8 pregnant rats were placed in equal numbers in slide flasks (chamber slides). One slide flask was placed in the clinostat and the other served as a stationary control. At 48 h in the clinostat, whereas the levels of progesterone and total cellular protein decreased, the number of shrunken cells increased. To determine whether apoptosis occurred in shrunken cells, Comet and TUNEL assays were performed. At 48 h, the percentage of apoptotic cells in the clinostat increased compared with that in the control. To investigate how the microgravity conditions induce apoptosis, the active mitochondria in luteal cells were detected with JC-1 dye. Cells in the control consisted of many active mitochondria, which were evenly distributed throughout the cell. In contrast, cells in the clinostat displayed fewer active mitochondria, which were distributed either to the outer edge of the cell or around the nucleus. These results suggest that mitochondrial dysfunction induced by clinostat rotation could lead to apoptosis in luteal cells and suppression of progesterone production.

  18. Stimulation of LH, FSH, and luteal blood flow by GnRH during the luteal phase in mares.

    PubMed

    Castro, T; Oliveira, F A; Siddiqui, M A R; Baldrighi, J M; Wolf, C A; Ginther, O J

    2016-03-01

    A study was performed on the effect of a single dose per mare of 0 (n = 9), 100 (n = 8), or 300 (n = 9) of GnRH on Day 10 (Day 0 = ovulation) on concentrations of LH, FSH, and progesterone (P4) and blood flow to the CL ovary. Hormone concentration and blood flow measurements were performed at hours 0 (hour of treatment), 0.25, 0.5, 1, 2, 3, 4, and 6. Blood flow was assessed by spectral Doppler ultrasonography for resistance to blood flow in an ovarian artery before entry into the CL ovary. The percentage of the CL with color Doppler signals of blood flow was estimated from videotapes of real-time color Doppler imaging by an operator who was unaware of mare identity, hour, or treatment dose. Concentrations of LH and FSH increased (P < 0.05) at hour 0.25 and decreased (P < 0.05) over hours 1 to 6; P4 concentration was not altered by treatment. Blood flow resistance decreased between hours 0 and 1, but the decrease was greater (P < 0.05) for the 100-μg dose than for the 300-μg dose. The percentage of CL with blood flow signals increased (P < 0.05) between hours 0 and 1 with no significant difference between the 100- and 300-μg doses. The results supported the hypothesis that GnRH increases LH concentration, vascular perfusion of the CL ovary, and CL blood flow during the luteal phase; however, P4 concentration was not affected.

  19. Nicotine Pretreatment Increases Dysphoric Effects of Alcohol in Luteal-Phase Female Volunteers

    PubMed Central

    Penetar, David M.; Kouri, Elena M.; McCarthy, Elissa M.; Lilly, Michelle M.; Peters, Erica N.; Juliano, Trisha M.; Lukas, Scott E.

    2009-01-01

    The present report shows that nicotine enhances some of alcohol’s positive and negative effects in women and that these effects are most pronounced during the luteal phase of the menstrual cycle. Ten low progesterone and 10 high progesterone/luteal-phase women received nicotine patch pretreatments (placebo or 21 mg) 3 hours before an alcohol challenge (0.4 g/kg). Subjective effects were recorded on mood adjective scales and the Addiction Research Center Inventory (ARCI). Heart rate and skin temperature were recorded. Luteal-phase women reported peak positive (e.g. “stimulated”) and peak negative effects (e.g. “clumsy”, “dizzy”) almost twice as great as low progesterone women. PMID:19440397

  20. Colour Doppler Ultrasonography as a Tool to Assess Luteal Function in Santa Inês Ewes.

    PubMed

    Figueira, L M; Fonseca, J F; Arashiro, Ekn; Souza-Fabjan, Jmg; Ribeiro, Acs; Oba, E; Viana, Jhm; Brandão, F Z

    2015-08-01

    The aim of this study was to evaluate luteal dynamics in the Santa Inês ewes using colour Doppler (CD) ultrasonography. Oestrus was synchronized in nulliparous females (n = 18), and subsequently, they were only teased (n = 6) or teased and mated (n = 12). Blood samples were collected daily for plasma progesterone (P4 ) concentrations. Ultrasonographic images of corpora lutea (CL) in CD mode were obtained for further analysis in its largest diameter. The CD mode allowed an early sequential monitoring of CL that was visualized by the first time 0.77 ± 0.62 days after ovulation, with luteal area 29.68 ± 13.21 mm(2) . During the luteogenesis, a progressive increase was observed, followed by a plateau of luteal area, vascularization area and plasma concentrations of P4 reaching maximum values in D11 (124.0 ± 38.0 mm(2) , 52.78 ± 24.08 mm(2) and 11.23 ± 4.89 ng/ml, respectively). In the luteolysis, the plasma concentrations of P4 decreased sharply, whereas luteal and vascularization area gradually. The vascularization area was positively correlated with plasma concentrations of P4 during the luteogenesis (r = 0.22) and luteolysis (r = 0.48). The luteal dynamics of Santa Inês ewes showed patterns similar to those observed in other sheep breeds studied. The CD ultrasonography has the potential to be used as a tool to assess luteal function in sheep.

  1. Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials

    PubMed Central

    Doblinger, Jakob; Cometti, Barbara; Trevisan, Silvia; Griesinger, Georg

    2016-01-01

    Objective To summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment. Design Data from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level. Setting University affiliated reproductive medicine unit. Patients Subcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30kg/m2. Interventions Subcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients. Main outcome measures Ongoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk. Results The administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk. Conclusion No statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support. PMID:26991890

  2. Outpatient management of severe early OHSS by administration of GnRH antagonist in the luteal phase: an observational cohort study

    PubMed Central

    2012-01-01

    Background Management of established severe OHSS requires prolonged hospitalization, occasionally in intensive care units, accompanied by multiple ascites punctures, correction of intravascular fluid volume and electrolyte imbalance. The aim of the present study was to evaluate whether it is feasible to manage women with severe OHSS as outpatients by treating them with GnRH antagonists in the luteal phase. Methods This is a single-centre, prospective, observational, cohort study. Forty patients diagnosed with severe OHSS, five days post oocyte retrieval, were managed as outpatients after administration of GnRH antagonist (0.25 mg) daily from days 5 to 8 post oocyte retrieval, combined with cryopreservation of all embryos. The primary outcome measure was the proportion of patients with severe OHSS, in whom outpatient management was not feasible. Results 11.3% (95% CI 8.3%-15.0%) of patients (40/353) developed severe early OHSS. None of the 40 patients required hospitalization following luteal antagonist administration and embryo cryopreservation. Ovarian volume, ascites, hematocrit, WBC, serum oestradiol and progesterone decreased significantly (P < 0.001) by the end of the monitoring period, indicating rapid resolution of severe OHSS. Conclusions The current study suggests, for the first time, that successful outpatient management of severe OHSS with antagonist treatment in the luteal phase is feasible and is associated with rapid regression of the syndrome, challenging the dogma of inpatient management. The proposed management is a flexible approach that minimizes unnecessary embryo transfer cancellations in the majority (88.7%) of high risk for OHSS patients. PMID:22938051

  3. Interpretation of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range.

    PubMed Central

    Wathen, N C; Perry, L; Lilford, R J; Chard, T

    1984-01-01

    Single serum progesterone determinations were made in 79 apparently normal women with a regular menstrual cycle. A normal range (40 subjects) was derived from the concentrations in the follicular phase and used to define an "anovular" range for luteal phase values (nine out of 39 subjects). The remaining luteal phase values were used to construct an "ovular" range for the luteal phase and, within this range, to define a group of values (less than the 20th centile) which could be described as a "defective luteal phase." The cut off limits between ovular and anovular and between normal and defective luteal phases were respectively two and four times the follicular phase median. It is proposed that the numerical findings of this study may be used as a rule of thumb for defining normality and abnormality from a single serum progesterone determination. PMID:6418326

  4. Logistic Regression

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-12-01

    The logistic regression originally is intended to explain the relationship between the probability of an event and a set of covariables. The model's coefficients can be interpreted via the odds and odds ratio, which are presented in introduction of the chapter. The observations are possibly got individually, then we speak of binary logistic regression. When they are grouped, the logistic regression is said binomial. In our presentation we mainly focus on the binary case. For statistical inference the main tool is the maximum likelihood methodology: we present the Wald, Rao and likelihoods ratio results and their use to compare nested models. The problems we intend to deal with are essentially the same as in multiple linear regression: testing global effect, individual effect, selection of variables to build a model, measure of the fitness of the model, prediction of new values… . The methods are demonstrated on data sets using R. Finally we briefly consider the binomial case and the situation where we are interested in several events, that is the polytomous (multinomial) logistic regression and the particular case of ordinal logistic regression.

  5. Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway.

    PubMed

    Di Bona, Danilo; Cippitelli, Marco; Fionda, Cinzia; Cammà, Calogero; Licata, Anna; Santoni, Angela; Craxì, Antonio

    2006-08-01

    Unresponsiveness to IFN-alpha is common in chronic hepatitis C. Since conditions associated with an increased oxidative stress (advanced age, steatosis, fibrosis, iron overload, and alcohol consumption) reduce the likelihood of response, we hypothesized that oxidative stress may affect the antiviral actions of IFN-alpha. We examined in a human hepatocellular carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a generator of oxidative stress, on the IFN-alpha signaling pathway. Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. The reduced expression of these genes was associated to H2O2 -mediated suppression of the IFN-alpha-induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFN-alpha-inducible genes. This was accomplished by preventing the IFN-alpha-induced tyrosine phosphorylation of STAT-1 and STAT-2 through the inactivation of the upstream receptor associated tyrosine kinases, JAK-1 and Tyk-2. The suppression was fast, occurring within 5mins of pretreatment with H2O2, and did not require protein synthesis. In conclusion, oxidative stress impairs IFN-alpha signaling and might cause resistance to the antiviral action of IFN-alpha in chronically HCV infected patients with high level of oxidative stress in the liver.

  6. Effect of Zanthoxylum schinifolium on TNF-alpha-induced vascular inflammation in human umbilical vein endothelial cells.

    PubMed

    Cao, Li Hua; Lee, Yun Jung; Kang, Dae Gill; Kim, Jin Sook; Lee, Ho Sub

    2009-01-01

    Pro-inflammatory cytokines induce the injury of endothelial cells in response to increases of adhesion molecules, leading to vascular inflammation and the development of atherosclerosis. In this study, we evaluated an ethanol extract of Zanthoxylum schinifolium (EZS) to determine if it inhibits the expressions of cellular adhesion molecules in human umbilical vein endothelial cells (HUVEC). When pretreatment of HUVEC with EZS, EZS suppressed the expression levels of cell adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-), and E-selectin induced by TNF-alpha. The adhesion of HL-60 cells to TNF-alpha-induced endothelial cells was decreased significantly in a concentration-dependent manner. Furthermore, TNF-alpha-induced MCP-1 and IL-8 mRNA expression levels were also attenuated by pretreatment with EZS. In addition, EZS suppressed TNF-alpha-induced production of reactive oxygen species (ROS). EZS inhibited NF-kappaB activation and IkappaB-alpha phosphorylation induced by TNF-alpha, subsequent degradation of IkappaB-alpha. Finally, EZS inhibited TNF-alpha-induced p38 MAPK and c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these results demonstrate that EZS suppresses vascular inflammatory process, which may be closely related to the inhibition of ROS, JNK, p38 MAPK and NF-kappaB activation in HUVEC.

  7. Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced cell damage in human renal proximal tubular epithelial cells.

    PubMed

    Kagawa, Toru; Takao, Toshihiro; Horino, Taro; Matsumoto, Reiko; Inoue, Kousuke; Morita, Tatsuhito; Hashimoto, Kozo

    2008-06-01

    We investigated the effect of angiotensin II (AII) type 1 (AT1) and angiotensin II type 2 (AT2) receptor blockers on tumour necrosis factor alpha (TNF-alpha)-induced cell damage in human renal proximal tubular epithelial cells (RPTEC). The lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) release into the medium after TNF-alpha treatment in RPTEC were determined using modified commercial procedures. In addition, the levels of caspase 3/7 activity in RPTEC were measured after TNF-alpha treatment with AlphaTau1 or AT2 receptor blockers. Finally we investigated the change of p22phox protein levels after TNF-alpha with AlphaTau1 or AT2 receptor blockers in RPTEC. Tumour necrosis factor alpha (10(-8) mol/L) significantly increased LDH and NAG release into the medium from RPTEC. AlphaTau1 receptor blockers, olmesartan and valsartan (10(-9)-10(-6) mol/L) showed a significant reduction on TNF-alpha-induced LDH and NAG release in RPTEC. AT2 receptor blocker, PD123319 (10(-7)-10(-5) mol/L) also decreased TNF-alpha-induced LDH and NAG release in RPTEC. Blockade of both AlphaTau1 and AT2 receptor indicated additional reduction on TNF-alpha-induced LDH and NAG release. TNF-alpha (10(-8) mol/L) treatment showed small but significant increases of caspase 3/7 activity in RPTEC, and AT1 and AT2 receptor blockers (10(-8) mol/L) comparably decreased TNF-alpha-induced caspase 3/7 activity. Significant increases of p22phox protein levels were observed in TNF-alpha-treated group in RPTEC. However, only AlphaTau1 (10(-8) mol/L) but not AT2 (10(-5) mol/L) receptor blocker significantly decreased TNF-alpha-induced p22phox protein levels. The present study demonstrates that TNF-alpha induces renal tubular cell damage in RPTEC and AT1/AT2 receptor blockers showed cytoprotective effects probably via at least partly different mechanism.

  8. A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer.

    PubMed

    Lee, Vivian Chi Yan; Li, Raymond Hang Wun; Yeung, William Shu Biu; Pak Chung, H O; Ng, Ernest Hung Yu

    2017-05-01

    Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate? The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate. The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone. This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015. Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days. The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET. This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support. The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET. No external funding was used and there were no competing interests. clinicaltrial.gov identifier: NCT01931384. 23/8/2013. 30/8/2013.

  9. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT DURING PREGNANCY

    EPA Science Inventory

    Effects of Bromodichloromethane (BDCM) on Ex Vivo Luteal Function In the Pregnant F344 Rat

    Susan R. Bielmeier1, Ashley S. Murr2, Deborah S. Best2, Jerome M. Goldman2, and Michael G. Narotsky2

    1Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC 27599,...

  10. Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role Redefined!!

    PubMed Central

    Malik, Sonia

    2016-01-01

    Role of progesterone in reproductive medicine is evolving with its suggested clinical role for the hormonal and nonhormonal actions in reproductive medicine. The main function of progesterone is to induce ‘secretory’ changes in endometrium that is further complimented by its immunomodulatory and anti-inflammatory actions. It positively modulates PIBF, NK cells and HOXA 10 genes for better implantation. MHRA recommends Serum Progesterone levels ≥14ng/ml in the mid-luteal phase for supporting pregnancy adequately. Oral Natural Micronized Progesterone SR formulation represents a therapeutic advance in this direction offering ‘therapeutic compliance’ with oral formulation while avoiding the local side effects related to long-term patient compliance in reproductive disorders. The formulation offers round the clock efficiency and efficacy with single dose administration thereby improving patient convenience and compliance. This formulation has been marketed globally since 1986 utilizing the well validated drug delivery system involving Methylcellulose base. The clinical utility of this formulation is further suggested especially in various conditions related with luteal phase insufficiency and Bad obstetric history (BOH) or luteal phase support in ART. The level of evidence has been quite robust with several clinical studies including Prescription Event Monitoring and Investigator initiated studies supporting the clinical role of oral NMP SR formulation especially in ‘Real world’ clinic settings for Luteal phase insufficiency that may be physiological or iatrogenic. PMID:27042538

  11. A controlled study of light therapy in women with late luteal phase dysphoric disorder.

    PubMed

    Lam, R W; Carter, D; Misri, S; Kuan, A J; Yatham, L N; Zis, A P

    1999-06-30

    Previous studies suggest that light therapy, as used to treat seasonal affective disorder, may be beneficial for pre-menstrual depressive disorders. We conducted a six-menstrual cycle randomized, double-blind, counter-balanced, crossover study of dim vs. bright light therapy in women with late luteal phase dysphoric disorder (LLPDD). Fourteen women who met DSM-III-R criteria for LLPDD completed two menstrual cycles of prospective baseline monitoring of pre-menstrual symptoms, followed by two cycles of each treatment. During the 2-week luteal phase of each treatment cycle, patients were randomized to receive 30 min of evening light therapy using: (1) 10000 lx cool-white fluorescent light (active condition); or (2) 500 lx red fluorescent light (placebo condition), administered by a light box at their homes. After two menstrual cycles of treatment, patients were immediately crossed over to the other condition for another two cycles. Outcome measures were assessed at the mid-follicular and luteal phases of each cycle. Results showed that the active bright white light condition significantly reduced depression and pre-menstrual tension scores during the symptomatic luteal phase, compared to baseline, while the placebo dim red light condition did not. These results suggest that bright light therapy is an effective treatment for LLPDD.

  12. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT

    EPA Science Inventory

    EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.

    S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive T...

  13. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT

    EPA Science Inventory

    EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.

    S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive T...

  14. Effects of IL8 and immune cells on the regulation of luteal progesterone secretion

    USDA-ARS?s Scientific Manuscript database

    Recent studies suggest that chemokines may mediate the luteolytic action of PGF2a (PGF). Our objective was to identify chemokines induced by PGF in vivo and to determine the effects of IL8 on specific luteal cell types in vitro. Midcycle cows were injected with saline or PGF, ovaries were removed ...

  15. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT

    EPA Science Inventory

    EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.

    S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive T...

  16. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT

    EPA Science Inventory

    EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.

    S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive T...

  17. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT DURING PREGNANCY

    EPA Science Inventory

    Effects of Bromodichloromethane (BDCM) on Ex Vivo Luteal Function In the Pregnant F344 Rat

    Susan R. Bielmeier1, Ashley S. Murr2, Deborah S. Best2, Jerome M. Goldman2, and Michael G. Narotsky2

    1Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC 27599,...

  18. Endometrial prostaglandin synthases, ovarian steroids, and oxytocin receptors in mares with oxytocin-induced luteal maintenance.

    PubMed

    Rebordão, Maria R; Galvão, António; Pinto-Bravo, Pedro; Pinheiro, Joana; Gamboa, Sandra; Silva, Elisabete; Mateus, Luísa; Ferreira-Dias, Graça

    2017-01-01

    Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin F2α, E2 and I2 synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration. Control mares (n = 5; C group) received 6 mL of saline im, whereas OXT (60 units/mare) was administered im (n = 6; OXT group), every 12 hours, on days 7 to 14 postovulation. After endometrial biopsy in groups C (Day 10) and OXT (Day 24), luteolysis occurred within 3 or 6 days, respectively. Luteal maintenance took place in 4 of 6 (67%) of OXT-treated mares. Progesterone in C group was the highest on biopsy day (P < 0.05). In OXT mares, PTGS2, ESR1 (P < 0.05), PTGES, PTGIS, PGR, and ESR2 (P < 0.01) gene transcription decreased, whereas OXTR increased (P < 0.05) in comparison with the C group. In OXT-treated mares, endometrial ESR2 protein expression decreased (P < 0.05), but OXTR increased (P < 0.05) compared with control animals. In both experimental groups, PTGS2 was mainly immunolocalized in surface epithelium, whereas AKR1C3, PTGES, PTGIS, and PGR were in surface and glandular epithelia. ESR1 and ESR2 were found in glandular epithelium and OXTR in stromal cells. High immunolabeling for PTGES, PTGIS, PGR, and OXTR and low for ESR2 was detected in endometrium of OXT-group mares with extended diestrus. Prolonged luteal function associated with chronic OXT treatment may be related to different spatial expression of OXTR and PGR in the endometrium. The observed reduction of endometrial ESR2 may be responsible for the maintenance of PGR in luminal and glandular

  19. Swainsonine differentially affects steroidogenesis and viability in caprine luteal cells in vitro.

    PubMed

    Huang, Yong; Li, Wei; Zhao, Xiaomin; Ding, Li; Yu, Gaoshui; Dong, Feng; Du, Qian; Xu, Xingang; Tong, Dewen

    2013-07-01

    Plants containing swainsonine (SW) have been reported to impair reproductive function and fertility after long-term ingestion by livestock. However, direct effects of SW on luteal cell steroidogenesis remain unclear. In this study, primary and transfected luteal cells were used to investigate the effects of SW on progesterone secretion and cell viability and the mechanisms involved in these processes. After treatment with various concentrations of SW for 24 or 48 hours, progesterone production and the number of living cells were assessed using radioimmunoassay and trypan blue dye exclusion assay, respectively. Lower concentrations of SW enhanced basal, 22R-hydroxycholesterol- or pregnenolone-stimulated progesterone secretion (P < 0.05), whereas higher concentrations of SW inhibited progesterone secretion (P < 0.05). Lower concentrations of SW promoted expression of P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase, two key enzymes involved in luteal cell steroidogenesis, at mRNA and protein levels (P < 0.05), but did not affect expression of steroidogenic acute regulatory protein and cell proliferation. In contrast, higher concentrations of SW inhibited luteal cell proliferation by inducing growth phase 1/quiescent state cell cycle arrest and apoptosis (P < 0.05). Taken together, these results demonstrated that lower concentrations of SW induced progesterone production through upregulation of P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase without affecting cell viability, whereas higher concentrations of SW induced cell cycle arrest and apoptosis and impaired steroidogenesis. These findings provided new insights into understanding the effect of SW on luteal cell steroidogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Fusion protein of CDR mimetic peptide with Fc inhibit TNF-alpha induced cytotoxicity.

    PubMed

    Qin, Weisong; Feng, Jiannan; Li, Yan; Lin, Zhou; Shen, Beifen

    2006-02-01

    The variable regions of antibodies play central roles in the binding with antigens. Based on the model of a tumour necrosis factor-alpha (TNF-alpha) neutralizing monoclonal antibody (named as Z12) with TNF-alpha, heavy chain CDR2 (HCDR2) and light chain CDR3 (LCDR3) of Z12 were found to be the most responsible to bind with TNF-alpha. A mimetic peptide (PT) was designed based on the sequence derived from HCDR2 and LCDR3. Fusion protein PT-Fc was constructed by linking PT with Fc of human IgG1 through a flexible linker (GGGGGS). The primary structural characteristics of Fc and PT-Fc were analyzed, including the flexibility, hydrophilicity and epitopes. It was demonstrated that PT and Fc in the fusion protein possessed bio-function properly and non-interfering with each other. Furthermore, PT-Fc was expressed in Escherichia coli by fusion with thioredoxin (Trx). After trx-PT-Fc was cleaved with recombinant enterokinase, PT-Fc was obtained. The results of in vitro cytotoxic assays showed that both PT and PT-Fc could efficiently inhibit TNF-alpha induced apoptosis on L929 cells. At the same micromole concentration, the inhibition activity of PT-Fc was significantly higher than PT.

  1. DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

    SciTech Connect

    Kuzuhara, T. Suganuma, M.; Oka, K.; Fujiki, H.

    2007-11-03

    Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggests a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.

  2. Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet-activating factor biosynthesis

    PubMed Central

    1994-01-01

    Tumor necrosis factor (TNF) alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Therefore, it was suggested that the angiogenic properties of this agent might be consequent to the production of secondary mediators. Since TNF-alpha stimulates the synthesis of platelet-activating factor (PAF) by monocytes and endothelial cells, we investigated the possible involvement of PAF in the angiogenic effect of TNF-alpha. Angiogenesis was studied in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model the angiogenesis induced by TNF-alpha was shown to be inhibited by WEB 2170, a specific PAF receptor antagonist. Moreover, in mice injected with TNF-alpha, PAF was detected within the Matrigel, 6 and 24 h after TNF-alpha injection. The synthesis of PAF within the Matrigel was concomitant with the early migration of endothelial cells and infiltration of monocytes. No infiltration of lymphocytes or polymorphonuclear leukocytes was observed. Synthetic PAF as well as PAF extracted and purified from mice challenged with TNF-alpha induced a rapid angiogenic response, inhibited by WEB 2170. These results suggest that the angiogenic effect of TNF-alpha is, at least in part, mediated by PAF synthesized from monocytes and/or endothelial cells infiltrating the Matrigel plug. PMID:7516414

  3. Mutation analysis of tumor necrosis factor alpha-induced protein 3 gene in Hodgkin lymphoma.

    PubMed

    Etzel, Barbara-Magdalena; Gerth, Melanie; Chen, Yuan; Wünsche, Elisa; Facklam, Tina; Beck, James F; Guntinas-Lichius, Orlando; Petersen, Iver

    2017-03-01

    Survival and proliferation of Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (CHL), are dependent on constitutive activation of nuclear factor kB (NF-κB). A20, encoded by TNF alpha-induced protein 3 (TNFAIP3), one of the inhibitors of NF-kB, was found to be inactivated by deletions and/or point mutations in CHL. TNFAIP3 mutations were examined in 37 patients with CHL by using PCR and direct sequencing. In addition, protein expression of A20 was evaluated by immunohistochemistry. Epstein-Barr virus (EBV) status of HL samples was determined by EBV EBER chromogenic in situ hybridization (ISH). We identified 8 mutation positive cases in a collective of 37 investigated cases (22%). Mutations were most frequent in the nodular sclerosis subtype. Our results revealed the tendency that cases harboring A20 mutations were negative for A20 staining. None of A20 mutation-positive CHL cases showed EBV infection. Our study confirms the involvement of the TNFAIP3 tumor suppressor gene in CHL. A20 may represent a suppressor of human lymphoma and provide a critical molecular link between chronic inflammation and cancer. None of A20 mutation-positive CHL cases showed EBV infection. This fact suggests complementing functions of TNFAIP3 inactivation and EBV infection in CHL pathogenesis and may represent an interesting point of further investigations. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. Interferon alpha-inducible protein 6 regulates NRASQ61K-induced melanomagenesis and growth

    PubMed Central

    Gupta, Romi; Forloni, Matteo; Bisserier, Malik; Dogra, Shaillay Kumar; Yang, Qiaohong; Wajapeyee, Narendra

    2016-01-01

    Mutations in the NRAS oncogene are present in up to 20% of melanoma. Here, we show that interferon alpha-inducible protein 6 (IFI6) is necessary for NRASQ61K-induced transformation and melanoma growth. IFI6 was transcriptionally upregulated by NRASQ61K, and knockdown of IFI6 resulted in DNA replication stress due to dysregulated DNA replication via E2F2. This stress consequentially inhibited cellular transformation and melanoma growth via senescence or apoptosis induction depending on the RB and p53 pathway status of the cells. NRAS-mutant melanoma were significantly more resistant to the cytotoxic effects of DNA replication stress-inducing drugs, and knockdown of IFI6 increased sensitivity to these drugs. Pharmacological inhibition of IFI6 expression by the MEK inhibitor trametinib, when combined with DNA replication stress-inducing drugs, blocked NRAS-mutant melanoma growth. Collectively, we demonstrate that IFI6, via E2F2 regulates DNA replication and melanoma development and growth, and this pathway can be pharmacologically targeted to inhibit NRAS-mutant melanoma. DOI: http://dx.doi.org/10.7554/eLife.16432.001 PMID:27608486

  5. Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-alpha-induced VCAM-1 expression.

    PubMed

    Meng, Charles Q; Zheng, X Sharon; Ni, Liming; Ye, Zhihong; Simpson, Jacob E; Worsencroft, Kimberly J; Hotema, Martha R; Weingarten, M David; Skudlarek, Jason W; Gilmore, Joshua M; Hoong, Lee K; Hill, Russell R; Marino, Elaine M; Suen, Ki-Ling; Kunsch, Charles; Wasserman, Martin A; Sikorski, James A

    2004-03-22

    Novel chalcone derivatives have been discovered as potent inhibitors of TNF-alpha-induced VCAM-1 expression. Thienyl or benzothienyl substitution at the meta-position of ring B helps boost potency while large substitution at the para-position on ring B is detrimental. Various substitutions are tolerated on ring A. A lipophilicity-potency relationship has been observed in several sub-series of compounds.

  6. Fish meal supplementation increases bovine plasma and luteal tissue omega-3 fatty acid composition.

    PubMed

    White, N R; Burns, P D; Cheatham, R D; Romero, R M; Nozykowski, J P; Bruemmer, J E; Engle, T E

    2012-03-01

    The objective of this experiment was to determine if dietary inclusion of fish meal would increase plasma and luteal tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Seventeen nonlactating Angus cows (2 to 8 yr of age) were housed in individual pens and fed a corn silage-based diet for approximately 60 d. Diets were supplemented with fish meal at 5% DMI (a rich source of eicosapentaenoic acid and docosahexaenoic acid; n = 9 cows) or corn gluten meal at 6% DMI (n = 8 cows). Body weights and jugular blood samples were collected immediately before the initiation of supplementation and every 7 d thereafter for 56 d to monitor plasma n-3 fatty acid composition and BW. Estrous cycles were synchronized using 2 injections of PGF(2α) administered at 14-d intervals. The ovary bearing the corpus luteum was surgically removed at midcycle (between d 10 and 12) after estrus synchronization, which corresponded to approximately d 60 of supplementation. The ovary was transported to the laboratory, and approximately 1.5 g of luteal tissue was stored at -80°C until analyzed for n-3 fatty acid content. Initial and ending BW did not differ (P > 0.10) between cows supplemented with fish meal and those with corn gluten meal. Plasma eicosapentaenoic acid was greater (P < 0.05) beginning at d 7 of supplementation and docosahexaenoic was greater (P < 0.05) beginning at d 14 of supplementation for cows receiving fish meal. Luteal tissue collected from fish meal-supplemented cows had greater (P < 0.05) luteal n-3 fatty acids and reduced (P < 0.05) arachidonic acid and n-6 to n-3 ratio as compared with tissue obtained from cows supplemented with corn gluten meal. Our data show that fish meal supplementation increases luteal n-3 fatty acid content and reduces available arachidonic acid content, the precursor for PGF(2α). The increase in luteal n-3 fatty acids may reduce PGF(2α) intraluteal synthesis after breeding resulting in increased fertility in cattle.

  7. The relationship between serum adiponectin and postpartum luteal activity in high-producing dairy cows.

    PubMed

    Kafi, Mojtaba; Tamadon, Amin; Saeb, Mehdi

    2015-05-01

    The aims of the present study were to initially determine the pattern of serum adiponectin concentrations during a normal estrous cycle in high-producing postpartum dairy cows and then evaluate the relationship between the serum concentrations of adiponectin and insulin with the commencement of postpartum luteal activity and ovarian activities in clinically healthy high-producing Holstein dairy cows. During a normal estrous cycle of cows (n = 6), serum adiponectin concentrations gradually decreased (P < 0.05) after ovulation by Day-17 estrous cycle and then increased before the next ovulation. Cows with higher peak of milk yield had lower serum adiponectin concentrations by week 7 postpartum (P = 0.01). Serum adiponectin and insulin concentrations in cows with different postpartum luteal activity (based on the progesterone profile) were evaluated using the following class of cows: normal (≤45 days, n = 11) and delayed (>45 days, n = 11) commencement of luteal activity (C-LA) and four different profiles of normal luteal activity (NLA, n = 5), prolonged luteal phase (n = 6), delayed first ovulation (n = 6), and anovulation (AOV, n = 5). Serum adiponectin concentrations decreased gradually by week 3 postpartum in NLA and then increased; whereas in AOV and delayed first ovulation, they were decreased after week 3 postpartum (P < 0.05). Moreover, serum adiponectin concentrations in NLA were more than AOV at weeks 5 and 7 postpartum (P = 0.05). The increase in the milk yield from weeks 1 to 7 postpartum in prolonged luteal phase (P = 0.05) and AOV (P = 0.04) cows was more than that of NLA cows. Insulin concentrations were almost maintained at a stable level in NLA cows (P > 0.05), whereas they increased in the other groups (P < 0.05). Moreover, adiponectin concentrations in cows with C-LA greater than 45 days decreased more than those with C-LA 45 days or less after week 3 postpartum (P = 0.002). Serum adiponectin concentrations at week 7 postpartum were lower in

  8. The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

    PubMed

    Luan, Y Y; Yao, Y M; Sheng, Z Y

    2013-01-01

    Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

  9. NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway

    SciTech Connect

    Kim, Nam Hee; Jung, Hye Jin; Shibasaki, Futoshi; Kwon, Ho Jeong

    2010-01-15

    Nuclear factor-{kappa}B (NF-{kappa}B) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene) propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-{kappa}B activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-{alpha})-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effect of NBBA on TNF-{alpha}-induced NF-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.

  10. Biodentine Reduces Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells.

    PubMed

    El Karim, Ikhlas A; McCrudden, Maelíosa T C; McGahon, Mary K; Curtis, Tim M; Jeanneau, Charlotte; Giraud, Thomas; Irwin, Chris R; Linden, Gerard J; Lundy, Fionnuala T; About, Imad

    2016-04-01

    The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. Immunofluorescent staining revealed TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha-induced TRPA1 responses after Biodentine treatment. In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Dehydroepiandrosterone inhibits the TNF-alpha-induced inflammatory response in human umbilical vein endothelial cells.

    PubMed

    Gutiérrez, Gisela; Mendoza, Criselda; Zapata, Estrella; Montiel, Angélica; Reyes, Elba; Montaño, Luis Felipe; López-Marure, Rebeca

    2007-01-01

    Dehydroepiandrosterone (DHEA) has a protective role against atherosclerosis. We determined the effect of pharmacological doses of DHEA upon the adhesion of monocytic U937 cells to human umbilical vein endothelial cells (HUVEC), as well as the expression of adhesion and chemoattractant molecules, the translocation of NF-kappaB, the degradation of IkappaB-alpha and the production of reactive oxygen species (ROS) in HUVEC. Adhesion of U937 cells to DHEA-treated HUVEC was evaluated by co-culture experiments using [(3)H]-thymidine-labeled U937 cells. The expression of adhesion and chemoattractant molecules was evaluated by flow cytometry and RT-PCR, respectively; NF-kappaB translocation was determined by Electrophoretic Mobility Shift Assay (EMSA) and IkappaB-alpha degradation by Western blot. ROS production was determined by the reduction of fluorescent DCFDA. TNF-alpha was used to induce inflammatory responses in HUVEC. One hundred micromolar of DHEA-treatment inhibited the TNF-alpha-induced expression of ICAM-1, E-selectin, ROS production and U937 cells adhesion to HUVEC, and interfered with NF-kappaB translocation and IkappaB-alpha degradation. DHEA at the above mention concentration also inhibited the mRNA expression of MCP-1 and IL-8 in basal conditions but not in TNF-alpha-stimulated conditions. Our results suggest that DHEA inhibits the expression of molecules involved in the inflammatory process, therefore it could be used as an alternative in the treatment of chronic inflammatory diseases such as atherosclerosis.

  12. Corpus luteum development and function after supplementation of long-acting progesterone during the early luteal phase in beef cattle.

    PubMed

    Pugliesi, G; Oliveria, M L; Scolari, S C; Lopes, E; Pinaffi, F V; Miagawa, B T; Paiva, Y N; Maio, J R G; Nogueira, G P; Binelli, M

    2014-02-01

    Strategic supplementation of P4 may be used to increase conception rates in cattle, but timing of supplementation in relation to ovulation, mass of supplementary P4 and formulation of the P4-containing supplement has not been determined for beef cattle. Effects of supplementation of long-acting progesterone (P4) on Days 2 or 3 post-ovulation on development, function and regression of corpus luteum (CL) were studied in beef cattle. Cows were synchronized with an oestradiol/P4-based protocol and treated with 150 or 300 mg of long-acting P4 on Day 2 or 3 post-ovulation (6-7 cows/group). Colour-doppler ultrasound scanning and blood sample collection were performed from Day 2-21.5. Plasma P4 concentrations were greater (p < 0.05) from Day 2.5-5.5 in the Day 2-treated groups and from Day 3.5-5.5 in the Day 3-treated cows than in the control group. CL area and blood flow during Day 2-8.5 did not differ (p > 0.05) among groups, suggesting no effect of P4 treatment on luteal development. The frequency of cows that began luteolysis before Day 15 was greater (p < 0.04) in cows treated with 300 mg than in the controls, but there were no differences between non-treated and 150 mg-treated cows. The interval from pre-treatment ovulation to functional and structural luteolysis was shorter (p < 0.01) in the combined P4-treated groups than in the control cows. In conclusion, was showed for the first time that long-acting P4 supplementation on Day 2 or 3 post-ovulation increases P4 concentrations for ≥3 day, has no effect on luteal development, but anticipates the beginning of luteolysis in beef cattle. © 2013 Blackwell Verlag GmbH.

  13. Influence of Reproductive Aging of the Cow on Luteal Function and Period 1 mRNA Expression

    USDA-ARS?s Scientific Manuscript database

    In rodents, disruption of the circadian clock genes results in increased incidence of anovulation, irregular estrous cycles, decreased luteal function, and accelerated reproductive ageing. In cattle, reproductive ageing is associated with decreased numbers of follicles in the ovary, decreased lutea...

  14. Luteinizing hormone inhibits conversion of pregnenolone to progesterone in luteal cells from rats on day 19 of pregnancy.

    PubMed

    Stocco, C O; Deis, R P

    1999-03-01

    We have previously reported that intrabursal ovarian administration of LH at the end of pregnancy in rats induces a decrease in luteal progesterone (P4) synthesis and an increase in P4 metabolism. However, whether this local luteolytic effect of LH is exerted directly on luteal cells or on other structures, such as follicular or stromal cells, to modify luteal function is unknown. The aim of the present study was to determine the effect of LH on isolated luteal cells obtained on Day 19 of pregnancy. Incubation of luteal cells with 1, 10, 100, or 1000 ng/ml of ovine LH (oLH) for 6 h did not modify basal P4 production. The addition to the culture medium of 22(R)-hydroxycholesterol (22R-HC, 10 microgram/ml), a membrane-permeable P4 precursor, or pregnenolone (10(-2) microM) induced a significant increase in P4 accumulation in the medium in relation to the control value. When luteal cells were preincubated for 2 h with oLH, a significant (p < 0.01) reduction in the 22R-HC- or pregnenolone-stimulated P4 accumulation was observed. Incubation of luteal cells with dibutyryl cAMP (1 mM, a cAMP analogue) plus isobutylmethylxanthine (1 mM, a phosphodiesterase inhibitor) also inhibited pregnenolone-stimulated P4 accumulation. Incubation with an inositol triphosphate synthesis inhibitor, neomycin (1 mM), or an inhibitor of intracellular Ca2+ mobilization, (8,9-N, N-diethylamino)octyl-3,4,5-trimethoxybenzoate (1 mM), did not prevent the decrease in pregnenolone-stimulated P4 secretion induced by oLH. It was concluded that the luteolytic action of LH in late pregnancy is due, at least in part, to a direct action on the luteal cells and that an increase in intracellular cAMP level might mediate this effect.

  15. Acetaminophen does not affect 24-h body temperature or sleep in the luteal phase of the menstrual cycle.

    PubMed

    Baker, Fiona C; Driver, Helen S; Paiker, Janice; Rogers, Geoffrey G; Mitchell, Duncan

    2002-04-01

    Body temperature and sleep change in association with increased progesterone in the luteal phase of the menstrual cycle in young women. The mechanism by which progesterone raises body temperature is not known but may involve prostaglandins, inducing a thermoregulatory adjustment similar to that of fever. Prostaglandins also are involved in sleep regulation and potentially could mediate changes in sleep during the menstrual cycle. We investigated the possible role of central prostaglandins in mediating menstrual-associated 24-h temperature and sleep changes by inhibiting prostaglandin synthesis with a therapeutic dose of the centrally acting cyclooxygenase inhibitor acetaminophen in the luteal and follicular phases of the menstrual cycle in young women. Body temperature was raised, and nocturnal amplitude was blunted, in the luteal phase compared with the follicular phase. Acetaminophen had no effect on the body temperature profile in either menstrual cycle phase. Prostaglandins, therefore, are unlikely to mediate the upward shift of body temperature in the luteal phase. Sleep changed during the menstrual cycle: on the placebo night in the luteal phase the women had less rapid eye movement sleep and more slow-wave sleep than in the follicular phase. Acetaminophen did not alter sleep architecture or subjective sleep quality. Prostaglandin inhibition with acetaminophen, therefore, had no effect on the increase in body temperature or on sleep in the midluteal phase of the menstrual cycle in young women, making it unlikely that central prostaglandin synthesis underlies these luteal events.

  16. Internalization of 125I-human choriogonadotropin in bovine luteal slices. A biochemical study.

    PubMed

    Chegini, N; Rao, C V; Carman, F R

    1984-04-01

    Various intracellular organelles as well as outer cell membranes of bovine corpora lutea intrinsically contain gonadotropin receptors (Rao et al., J biol chem 256 (1981) 2628 [5]). In order to investigate whether exogenously added human choriogonadotropin (hCG) can internalize and bind to the intracellular sites, bovine luteal slices that had been carefully checked with respect to structural and functional integrity were incubated with 0.1 nM 125I-hCG. Following incubation, specific radioactivity was found to be associated with various intracellular organelles, but not with cytosol. The order of radioactivity uptake by subcellular organelles following a 2-h incubation was: Golgi medium greater than Golgi heavy greater than Golgi light greater than plasma membranes = rough endoplasmic reticulum greater than mitochondria-lysosomes- greater than nuclei. The 5'-nucleotidase activity and electron microscopic examination of the fractions revealed that the presence of radioactivity in the intracellular organelles cannot be attributed solely to plasma membrane contamination. The internalization and intracellular binding of 125I-hCG was time and temperature-dependent. Only excess unlabeled hCG and hLH (but not hCG subunits, FSH and PRL) competed with 125I-hCG for internalization in luteal slices. Very little or no 125I-hCG added was internalized in liver or kidney slices; luteal, liver and kidney slices accumulated neither 125I-BSA nor 125I. The radioactivity eluted from various luteal subcellular organelles was able to rebind to fresh corresponding organelles and came off Sepharose 6B columns in a position corresponding to native 125I-hCG. The gel filtration profile of detergent-solubilized radioactivity revealed that 125I-hCG was macromolecular bound. The degraded and altered 125I-hCG was found in the incubation media.

  17. Luteal Phase Dynamics of Follicle Stimulating and Luteinizing Hormones in Obese and Normal Weight Women

    PubMed Central

    Roth, Lauren W.; Allshouse, Amanda A.; Bradshaw-Pierce, Erica L.; Lesh, Jennifer; Chosich, Justin; Kohrt, Wendy; Bradford, Andrew P.; Polotsky, Alex J.; Santoro, Nanette

    2014-01-01

    Summary Objectives Female obesity is a state of relative hypogonadotrophic hypogonadism. The aim of this study is to examine gonadotrophin secretion and response to GnRH in the luteal phase of the menstrual cycle and to investigate the pharmacodynamics and pharmacokinetics of endogenous and exogenous LH in obese women. Design Participants underwent a luteal phase frequent blood sampling study. Endogenous LH pulsatility was observed, gonadotrophin releasing hormone (GnRH) was given in 2 weight based doses, and GnRH antagonist was administered followed by recombinant LH. Patients Regularly menstruating obese (n=10) and normal weight (n=10) women Measurements Endogenous hypothalamic-pituitary function (as measured by LH pulsatility), pituitary sensitivity (GnRH induced LH secretion), pharmacodynamics of endogenous LH, and pharmacokinetics of exogenous LH were compared between the obese and normal weight groups. Results There were no statistically significant differences in endogenous LH pulsatility or pituitary responses to two weight-based doses of GnRH between the obese and normal weight women. There were no differences in the pharmacodynamics of endogenous LH or the pharmacokinetics of exogenous LH between the groups. FSH dynamics did not differ between the groups throughout the study. Conclusions The relative hypogonadotrophic hypogonadism of obesity cannot be explained by differences in LH and FSH luteal phase dynamics or differences in endogenous LH pharmacodynamics or exogenous LH pharmacokinetics. Clinical trial registration number NCT01457703, www.clinicaltrials.gov PMID:24576183

  18. Luteal phase HCG support for unexplained recurrent pregnancy loss - a low hanging fruit?

    PubMed

    Fox, Chelsea; Azores-Gococo, Denise; Swart, Linda; Holoch, Kristin; Savaris, Ricardo F; Likes, Creighton E; Miller, Paul B; Forstein, David A; Lessey, Bruce A

    2017-03-01

    Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies and accounts for only 1-5% of pregnancy failures. Treatment options for unexplained RPL (uRPL) are limited. Previous studies suggest a link between delayed implantation and pregnancy loss. Based on this, a timely signal for rescue of the corpus luteum (CL) using human chorionic gonadotrophin (HCG) could improve outcomes in women with uRPL. This retrospective cohort study included 98 subjects with uRPL: 45 underwent 135 monitored cycles without HCG support; and 53 underwent 142 cycles with a single mid-luteal HCG injection. Based on Log-rank Mantel-Cox survival curves, miscarriage rate and time to pregnancy decreased in the HCG group (P = 0.0005). Women receiving luteal HCG support had an increased chance of an ongoing pregnancy compared with those not receiving it (RR = 2.4; 95% CI 1.4-3.6; number need to treat (NNT) = 7; 95% CI 4-18). Subjects receiving HCG support had a significant absolute risk reduction (ARR) of miscarriage (P < 0.001; ARR = 11.5%; 95% CI 3.6-19.5; NNT = 9(5-27). These data suggest restoration of synchrony and CL support improves outcomes in women with RPL. Further randomized controlled trials of luteal-phase HCG in women with RPL appears warranted. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Timing luteal support in ART: a systematic review F & S 19112 revision non-highlighted

    PubMed Central

    Connell, Matthew T.; Szatkowski, Jennifer M.; Terry, Nancy; DeCherney, Alan H.; Propst, Anthony M.; Hill, Micah J.

    2015-01-01

    Objective To summarize the available published randomized controlled trial data regarding timing of progesterone supplementation during the luteal phase of patients undergoing ART. Design A systematic review. Setting Not applicable. Patient(s) Undergoing in vitro fertilization. Intervention(s) Different starting times of progesterone for luteal support. Main Outcome Measure(s) Clinical pregnancy and live birth. Results Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed due to a high degree of clinical heterogeneity in regards to the timing, dose, and route of progesterone. Two studies compared progesterone initiated before oocyte retrieval versus the day of oocyte retrieval and pregnancy rates were 5–12% higher when starting progesterone on the day of oocyte retrieval. One study compared starting progesterone on post retrieval day 6 versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing progesterone start times on the day of oocyte retrieval versus two or three days post retrieval showed no significant differences in pregnancy. Conclusions There appears to be a window for progesterone start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. While some studies have suggested a potential benefit in delaying vaginal progesterone start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define progesterone start time for luteal support after ART. PMID:25638420

  20. N-acetylcysteine impairs survival of luteal cells through mitochondrial dysfunction.

    PubMed

    Löhrke, Berthold; Xu, Jinxian; Weitzel, Joachim M; Krüger, Burkhard; Goldammer, Tom; Viergutz, Torsten

    2010-04-01

    N-acetylcysteine (NAC) is known as an antioxidant and used for mucus viscosity reduction. However, this drug prevents or induces cell death depending on the cell type. The response of steroidogenic luteal cells to NAC is unknown. Our data shows that NAC can behave as an antioxidant or prooxidant in dependency on the concentration and mitochondrial energization. NAC elevated the flowcytometric-measured portion of hypodiploid (dying) cells. This rise was completely abolished by aurintricarboxylic acid, an inhibitor of topoisomerase II. NAC increased the secretion of nitric oxide and cellular nitrotyrosine. An image analysis indicated that cells pretreated with NAC and loaded with DHR showed a fluorescent structure probably elicited by the oxidative product of DHR, rhodamine 123 that sequesters mitochondrially. Pretreating luteal cells with NAC or adding NAC directly to mitochondrial fractions followed by assessing the mitochondrial transmembrane potential difference (Deltapsi) by the JC-1 technique demonstrated a marked decrease in Deltapsi. A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering. Thus, in steroidogenic luteal cells from healthy mature corpus luteum, NAC impairs cellular survival by interfering with mitochondrial metabolism. The protonophore-induced recovering of NAC-provoked decrease in Deltapsi indicates that an ATP synthase-favored route of H(+) re-entry to the matrix is essentially switched off by NAC while other respiratory chain complexes remain intact. These data may be important for therapeutic timing of treatments with NAC. (c) 2010 International Society for Advancement of Cytometry.

  1. A specific profile of luteal phase progesterone is associated with the development of premenstrual symptoms.

    PubMed

    Lovick, Thelma A; Guapo, Vinicius G; Anselmo-Franci, Janete A; Loureiro, Camila M; Faleiros, Maria Clara M; Del Ben, Cristina M; Brandão, Marcus L

    2017-01-01

    There is a consensus that the development of premenstrual dysphoric states is related to cyclical change in gonadal hormone secretion during the menstrual cycle. However, results from studies seeking to link symptom severity to luteal phase progesterone concentration have been equivocal. In the present study we evaluated not only the absolute concentrations of progesterone but also the kinetics of the change in progesterone concentration in relation to development of premenstrual symptoms during the last 10days of the luteal phase in a population of 46 healthy young adult Brazilian women aged 18-39 years, mean 26.5±6.7years. In participants who developed symptoms of premenstrual distress, daily saliva progesterone concentration remained stable during most of the mid-late luteal phase, before declining sharply during the last 3days prior to onset of menstruation. In contrast, progesterone concentration in asymptomatic women underwent a gradual decline over the last 8days prior to menstruation. Neither maximum nor minimum concentrations of progesterone in the two groups were related to the appearance or severity of premenstrual symptoms. We propose that individual differences in the kinetics of progesterone secretion and/or metabolism may confer differential susceptibility to the development of premenstrual syndrome.

  2. Levonorgestrel inhibits luteinizing hormone-stimulated progesterone production in rat luteal cells.

    PubMed

    Tellería, C M; Carrizo, D G; Deis, R P

    1994-08-01

    The effects of the synthetic progestin levonorgestrel (LNG) on basal and LH-stimulated progesterone production were studied in collagenase-dispersed luteal cells obtained from 9-day pregnant rats. Luteal cells responded to ovine LH (oLH) with an increase in progesterone output which was maximal at a dose of 100 ng/ml. No effect of LNG was observed at 0.1-10 microM, but at 100 microM, it inhibited basal progesterone production. On the other hand, a dose of 10 microM LNG suppressed the stimulation of progesterone secretion induced by oLH, dibutyryl-cAMP and pregnenolone. It is suggested that the possible mechanism of action of the progestin involves a post-cAMP site and, in some way, may lead to an interference with 3 beta-hydroxysteroid dehydrogenase activity, which catalyzes the formation of progesterone from pregnenolone, the last step of progesterone biosynthesis. This study provides a different point of view supporting an autocrine control mechanism by which progesterone, the principal steroidogenic product of luteal cells, may exert a negative ultra-short loop regulation of its own biosynthesis.

  3. Decreased progesterone receptor isoform expression in luteal phase fallopian tube epithelium and high-grade serous carcinoma

    PubMed Central

    Tone, Alicia A; Virtanen, Carl; Shaw, Patricia A; Brown, Theodore J

    2011-01-01

    We previously reported that BRCA1/2-mutated fallopian tube epithelium (FTE) collected during the luteal phase exhibits gene expression profiles more closely resembling that of high-grade serous carcinoma (HGSC) specimens than FTE collected during the follicular phase or from control patients. Since the luteal phase is characterised by high levels of progesterone, we determined whether the expression of progesterone receptor (PR) and PR-responsive genes was altered in FTE obtained from BRCA mutation carriers during the luteal phase of the menstrual cycle. RT-qPCR confirmed a decreased expression of PR mRNA in FTE during the luteal phase relative to follicular phase, in both BRCA1/2 mutation carriers and control patients. Immunohistochemistry using isoform-specific antibodies confirmed a low level of both PR-A and PR-B in HGSC and a lower level of staining in FTE samples obtained during the luteal phase compared with the follicular phase. No significant difference in PR-A or PR-B staining was found based on patient BRCA mutation status. Analysis of our previously reported gene expression profiles based upon known PR-A- and PR-B-specific target genes did not partition samples by BRCA mutation status, indicating that overall FTE PR response is not altered in BRCA mutation carriers. HGSC samples grouped separately from other samples, consistent with the observed loss of PR expression. These findings indicate no overall difference in PR signalling in FTE as a function of BRCA mutation status. Thus, the molecular similarity of BRCA1/2-mutated luteal phase FTE and HGSC likely results from an altered response to luteal phase factors other than progesterone. PMID:21263043

  4. Development of a bovine luteal cell in vitro culture system suitable for co-culture with early embryos.

    PubMed

    Batista, M; Torres, A; Diniz, P; Mateus, L; Lopes-da-Costa, L

    2012-10-01

    The cross talk between the corpus luteum (CL) and the early embryo, potentially relevant to pregnancy establishment, is difficult to evaluate in the in vivo bovine model. In vitro co-culture of bovine luteal cells and early embryos (days 2-8 post in vitro fertilization) may allow the deciphering of this poorly understood cross talk. However, early embryos and somatic cells require different in vitro culture conditions. The objective of this study was to develop a bovine luteal cell in vitro culture system suitable for co-culture with early embryos in order to evaluate their putative steroidogenic and prostanoid interactions. The corpora lutea of the different stages of the estrous cycle (early, mid, and late) were recovered postmortem and enriched luteal cell populations were obtained. In experiments 1 and 2, the effects of CL stage, culture medium (TCM, DMEM-F12, or SOF), serum concentration (5 or 10%), atmosphere oxygen tension (5 or 20%), and refreshment of the medium on the ability of luteal cells to produce progesterone (P(4)) were evaluated. The production of P(4) was significantly increased in early CL cultures, and luteal cells adapted well to simple media (SOF), low serum concentrations (5%), and oxygen tensions (5%). In experiment 3, previous luteal cell cryopreservation did not affect the production of P(4), PGF(2α), and PGE(2) compared to fresh cell cultures. This enables the use of pools of frozen-thawed cells to decrease the variation in cell function associated with primary cell cultures. In experiment 4, mineral oil overlaying culture wells resulted in a 50-fold decrease of the P(4) quantified in the medium, but had no effect on PGF(2α) and PGE(2) quantification. In conclusion, a luteal cell in vitro culture system suitable for the 5-d-long co-culture with early embryos was developed.

  5. Inhibitory effect of polyphenol cyanidin on TNF-alpha-induced apoptosis through multiple signaling pathways in endothelial cells.

    PubMed

    Xu, Jin-Wen; Ikeda, Katsumi; Yamori, Yukio

    2007-08-01

    The aim of this study was to investigate the inhibitory effect of non-aglycone cyanidin on TNF-alpha-induced endothelial cell apoptosis and its mechanism through enhancing expression of thioredoxin in endothelial cells. We found that exposure of the serum-starved BAECs to TNF-alpha increased significantly the number of dead cells, the cleaved caspase-3 and cleaved poly(ADP-ribose)polymerase (RARP)assayed by Western blot, whereas supplementation with cyanidin considerably suppressed these events. Inhibitors of the Akt, ERK1/2, Src kinase and transfection with a dominant-negative Akt cDNA blocked the inhibitory effect of cyanidin on cleaved caspase-3. Cyanidin significantly elevated expression of endothelial nitric oxide synthase (eNOS) and thioredoxin (Trx). The increased Trx expression was blocked by siRNA transfection of cGMP-dependent protein kinase (PKG) and by using a PKG inhibitor, KT5823. Cyanidin also ameliorated TNF-alpha-induced decrease of Trx S-nitrosylation and intracellular glutathione and elevation of 4-hydroxynonenal (4-HNE), a major aldehydic product of lipid peroxidation. Furthermore, cyanidin also restored S-nitrosylation of caspase-3 and reduced the rise in expression and acetylation of tumor suppression gene p53. However, KT5823 or L-NAME, an inhibitor of eNOS, removed the preventive effects of cyanidin. Our data show that inhibitory effect of cyanidin on TNF-alpha-induced apoptosis involves multiple pathways, such as Akt activation, eNOS and thioredoxin expression in endothelial cells.

  6. Alpha-induced reaction cross-section for Sm, U, Np targets: influence of hexadecapole deformation and deformed surface diffuseness

    NASA Astrophysics Data System (ADS)

    Alavi, S. A.; Dehghani, V.

    2017-06-01

    Alpha-induced reactions on 154Sm, 233,235,236,238U, and 237Np deformed nuclei are studied theoretically. The effects of hexadecapole deformation, deformed surface diffuseness parameter, and orientation on barrier height and position, fusion cross-section at any angle, and fusion cross-section have been investigated. Both hexadecapole deformation and deformed surface diffuseness can affect barrier characteristics and enhance fusion cross-section. Good agreement between experimental data and theoretical calculations with quadrupole and hexadecapole deformation and deformed surface diffuseness were observed for the 4He+154Sm, 235U, 237Np reactions.

  7. Characterization of luteal dynamics in lactating Holstein cows for 32 days after synchronization of ovulation and timed artificial insemination.

    PubMed

    Ricci, A; Carvalho, P D; Amundson, M C; Fricke, P M

    2017-10-04

    Approximately 20 to 30% of cows diagnosed not pregnant 32 d after timed artificial insemination (TAI) lack a corpus luteum (CL), and cows submitted to a resynchronization protocol in the absence of a CL have about 10% fewer pregnancies per AI (P/AI) than cows with a CL. An understanding of luteal dynamics after synchronization of ovulation and TAI may help refine strategies for reinseminating cows failing to conceive. Lactating Holstein cows (n = 141) were synchronized for first TAI using a Double-Ovsynch protocol. Thrice weekly from 4 to 32 d after TAI, blood samples were collected for evaluation of plasma progesterone (P4) concentrations, and CL diameter was measured using transrectal ultrasonography. Pregnancy status was determined using transrectal ultrasonography 32 d after TAI. Nonsynchronized cows (n = 4) were removed from the study. For cows diagnosed pregnant 32 d after TAI (n = 57), P4 increased from 4 to 15 d and then remained constant until 32 d after TAI, whereas CL volume increased from 4 to 11 d and then remained constant until 32 d after TAI. For cows diagnosed not pregnant 32 d after TAI (n = 80), P4 profiles were evaluated using statistical cluster analysis based on the day after TAI that P4 decreased to <1 ng/mL, resulting in 5 clusters: (1) CL regression 15 d after TAI (1.3%), (2) CL regression 18 to 22 d after TAI (55.0%), (3) CL regression 25 to 27 d after TAI (17.5%), (4) CL regression 29 to 32 d after TAI (5.0%), and (5) CL maintained until 32 d after TAI (21.3%). Plasma pregnancy-associated glycoprotein (PAG) levels at 25 and 32 d after TAI differed among clusters and were below the cut-off value of the assay for the classification of cows as not pregnant for cows in clusters 2, 3, and 4, whereas more than half of the cows in cluster 5 had increased plasma PAG levels. We conclude that at least half of the nonpregnant cows that maintained their CL until 32 d after TAI were initially pregnant but underwent early pregnancy loss based on

  8. Effect of exogenous progesterone supplementation in the early luteal phase post-insemination on pregnancy per artificial insemination in Holstein-Friesian cows.

    PubMed

    Parr, M H; Crowe, M A; Lonergan, P; Evans, A C O; Rizos, D; Diskin, M G

    2014-11-10

    One of the main determining factors of pregnancy per artificial insemination (P/AI) is an optimum concentration of progesterone (P4) in the early luteal phase. This study examined the effects of P4 supplementation on P/AI in lactating Holstein-Friesian cows. A total of 453 cows in 8 spring-calving herds were used in the study. Following AI, cows were randomly assigned to 1 of 2 treatment groups: (1) no subsequent treatment (control; n=221); (2) insertion of a Controlled Internal Drug Release device (CIDR) from day 4 to day 9 post-estrus (supplemented; n=232). Pregnancy per AI was determined by transrectal ultrasonography at day 30 following AI. Insertion of a CIDR increased concentrations of milk P4 in supplemented cows by 4.78ng/mL between day 4 and 4.5 in comparison with a 0.55ng/mL increase in control cows. Progesterone supplementation from day 4 to 9 after AI decreased P/AI by 12 percentage points (56 vs 44%). There was a positive linear and quadratic relationship between P/AI and milk concentration of P4 on day 4 post-estrus in control cows. An optimum concentration of 2.5ng/mL on day 4 was calculated from the logistic regression curve to achieve a probability of P/AI of 65%. When both treatments groups were included in the analysis, there was no association between P/AI and concentrations of P4 on day 4. The results of the study indicate that supplementation with P4 initiated in the early luteal phase had a negative effect on P/AI in dairy cows. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Involvement of stomach ghrelin and hypothalamic neuropeptides in tumor necrosis factor-alpha-induced hypophagia in mice.

    PubMed

    Endo, Mizuki; Masaki, Takayuki; Seike, Masataka; Yoshimatsu, Hironobu

    2007-04-05

    This study aimed to clarify the interaction of tumor necrosis factor-alpha (TNF-alpha), an anorexigenic cytokine, with ghrelin, an orexigenic peptide secreted by the stomach lining, and hypothalamic neuropeptides in the regulation of food intake in mice. The peripheral administration of TNF-alpha dose-dependently decreased the 24-h cumulative food intake compared with the administration of saline. Reduced food intake was observed at 6 h and 24 h. The same TNF-alpha treatment significantly decreased the plasma level of ghrelin at 6 h and 24 h after treatment compared with the control levels. These changes were accompanied by a significant reduction in the expression of ghrelin mRNA in the stomach at 24 h after treatment. TNF-alpha treatment also resulted in a significant increase in expression of pro-opiomelanocortin (POMC) mRNA and a significant decrease in expression of agouti-related protein (AGRP) mRNA in the hypothalamus at 6 h after treatment. Finally, the pre-administration of ghrelin, reversed the TNF-alpha-induced hypophagia in mice at 6 and 24 h. Taken together, these findings suggest that hypothalamic POMC and AGRP and stomach ghrelin may be involved in TNF-alpha-induced hypophagia in mice.

  10. [Protection effect of amentoflavone in Selaginella tamariscina against TNF-alpha-induced vascular injury of endothelial cells].

    PubMed

    Zheng, Xiao-ke; Liu, Cai-xia; Zhai, Ying-ying; Li, Ling-ling; Wang, Xiao-lan; Feng, Wei-sheng

    2013-09-01

    This study is to observe the protection effect of amentoflavone (AMT) in Selaginella tamariscina against TNF-alpha-induced vascular inflammation injury of endothelial cells. On the basis of TNF-alpha induced human umbilical vein endothelial cell, observe the influence of AMT on endothelial active factor, the contents of SOD and MDA, the protein expression of vascular endothelial adhesion molecules and inflammatory factor; study the effect of its common related signal pathways such as NF-kappaB; research the effect of AMT against TNF-a induced human umbilical vein endothelial cell injury by means of MTT, ELISA, Western blotting and the cell immunofluorescence. The results showed that AMT could increase the content of NO and decrease the levels of VCAM-1, E-selectin, IL-6, IL-8 and ET-1; enhance the activity of SOD, reduce the content of MDA; downregulate the protein expressions of VCAM-1, E-selectin, NF-kappaBp65 and up-regulate IkappaBalpha, attenuate the NF-kappaBp65 transfer to cell nucleus. AMT has the effect of protect vascular endothelial and maybe via the signal pathway of NF-kappaB to down-regulate the inflammation factor and oxidative damage factor of downstream.

  11. Inhibitory effects of ginger oil on spontaneous and PGF2alpha-induced contraction of rat myometrium.

    PubMed

    Buddhakala, Nopparat; Talubmook, Chusri; Sriyotha, Poonsook; Wray, Susan; Kupittayanant, Sajeera

    2008-03-01

    Solvent extracts of ginger, the rhizome of Zingiber officinale Roscoe (Zingiberaceae), have been extensively studied for their pharmacological activities in smooth muscles. However, the effects of ginger essential oil on smooth muscle contractility have not been elucidated. The aims of the study were to investigate the effects of ginger oil on rat myometrial contractility. We particularly examined the effects on phasic contractions arising either spontaneously or with PGF (2) (alpha) stimulation. Ginger oil was obtained by hydrodistillation and its constituents analyzed using gas chromatography and mass spectrometry. Rats were humanely killed by asphyxiation with CO (2), and longitudinal uterine smooth muscles were isolated. Isometric force was measured and the effects of ginger oil studied. It was found that citral was the main constituent of ginger oil (24 %). Ginger oil inhibited spontaneous contractions with an IC (50) of 50 microL/100 mL (10 - 150 microL/100 mL). The PGF (2) (alpha)-induced contractions were also significantly reduced by ginger oil. Increases in external calcium concentration completely reversed the relaxant effects of ginger oil. This was the case for both spontaneous and PGF (2) (alpha)-induced contractions. The effects of ginger oil were indistinguishable from those of pure citral. In conclusion, ginger oil is a potent inhibitor of phasic activity in rat uterus, irrespective of how it was produced. Our data suggest that the effects are largely due to citral, and could be via inhibition of L-type Ca channels.

  12. Increasing the dosage of progesterone (P) supplemention from the mid-luteal phase in women not attaining a mid-luteal homogeneous hyperechogenic (HH) pattern with sonography improves pregnancy rates (PRS) following frozen embryo transfer (ET).

    PubMed

    Check, J H; Dietterich, C; Cohen, R; Choe, J K; Amui, J; Brasile, D

    2010-01-01

    To determine if a mid-luteal phase non-homogeneous hyperechogenic (HH) endometrial echo pattern may lower pregnancy rates following frozen embryo transfer and to determine if raising the dosage of progesterone improves pregnancy outcome. Women not attaining an HH pattern at the mid-luteal phase following estrogen-progesterone replacement were randomly given (or not) an increase in progesterone dosage. Increasing the progesterone dosage in those not attaining an HH pattern significantly improved the pregnancy rate relative to controls not attaining an HH pattern and showed a trend for higher pregnancy rates than those with an HH pattern. The mid-luteal phase echo pattern should be evaluated for a non-HH pattern so that an increase in progesterone dosage could be provided possibly resulting in higher pregnancy rates.

  13. Sex steroids and personality traits in the middle luteal phase of healthy normally menstruating young professional women.

    PubMed

    Avgoustinaki, Pavlina D; Mitsopoulou, Effrosyni; Chlouverakis, Gregorios; Triantafillou, Theoni; Venihaki, Maria; Koukouli, Sofia; Margioris, Andrew N

    2012-01-01

    Sex steroids affect human behavior. The aim of the present study was to determine the associations, if any, between the circulating levels of gonadal and adrenal sex steroids in the mid luteal phase (21st day of a normal menstrual cycle, MC) of young professional women and psychometric parameters as assessed by the Minnesota Multiphasic Personality Inventory (MMPI). Our results are as follows: (a) The metabolic product of activated adrenal and gonadal androgens, 3alpha-diolG, was modestly but significantly associated with the social introversion scale (10-SI) (r=0.36, p<0.05), independently accounting for 13% of its variation across participants (R²=0.13, F(1,45)=6.58, p=0.014). (b) Total testosterone was significantly associated with the paranoia scale (6-Pa) (r=0.27, p<0.05). Multiple regression analyses indicated that 10% of the variability in paranoia scores could be independently explained by total testosterone levels (R²=0.10, F(1,57)=6.23, p=0.016). We were unable to find any association between the circulating androgens and scores on the masculinity-femininity scale (Mf). We were also unable to document any association between the weak adrenal androgens DHEA and DHEA-S and depression in contrast to several published reports. (c) Our data suggest a marginally significant association between progesterone and scores on the 7-Pt (obsessive/compulsive/psychasthenia) scale (r=0.27, p<0.05). However, only 7% of the 7-Pt variance was explained by progesterone (R²=0.071, F(1,50)=3.81, p=0.057). We have found that total testosterone was associated with the paranoia score, the metabolic product of activated androgens, 3alpha-diolG, to social introversion and, finally, progesterone to obsessive-compulsive behavior.

  14. Novel concepts on the role of prostaglandins on luteal maintenance and maternal recognition and establishment of pregnancy in ruminants.

    PubMed

    Arosh, Joe A; Banu, Sakhila K; McCracken, John A

    2016-07-01

    In ruminants, the corpus luteum (CL) of early pregnancy is resistant to luteolysis. Prostaglandin (PG)E2 is considered a luteoprotective mediator. Early studies indicate that during maternal recognition of pregnancy (MRP) in ruminants, a factor(s) from the conceptus or gravid uterus reaches the ovary locally through the utero-ovarian plexus (UOP) and protects the CL from luteolysis. The local nature of the embryonic antiluteolytic or luteoprotective effect precludes any direct effect of a protein transported or acting between the gravid uterus and CL in ruminants. During MRP, interferon tau (IFNT) secreted by the trophoblast of the conceptus inhibits endometrial pulsatile release of PGF2α and increases endometrial PGE2. Our recent studies indicate that (1) luteal PG biosynthesis is selectively directed toward PGF2α at the time of luteolysis and toward PGE2 at the time of establishment of pregnancy (ESP); (2) the ability of the CL of early pregnancy to resist luteolysis is likely due to increased intraluteal biosynthesis and signaling of PGE2; and (3) endometrial PGE2 is transported from the uterus to the CL through the UOP vascular route during ESP in sheep. Intrauterine co-administration of IFNT and prostaglandin E2 synthase 1 (PGES-1) inhibitor reestablishes endometrial PGF2α pulses and regresses the CL. In contrast, intrauterine co-administration of IFNT and PGES-1 inhibitor along with intraovarian administration of PGE2 rescues the CL. Together, the accumulating information provides compelling evidence that PGE2 produced by the CL in response to endometrial PGE2 induced by pregnancy may counteract the luteolytic effect of PGF2α as an additional luteoprotective mechanism during MRP or ESP in ruminants. Targeting PGE2 biosynthesis and signaling selectively in the endometrium or CL may provide luteoprotective therapy to improve reproductive efficiency in ruminants. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights

  15. Fibroblast growth factor 2 is a key determinant of vascular sprouting during bovine luteal angiogenesis.

    PubMed

    Woad, Kathryn J; Hunter, Morag G; Mann, George E; Laird, Mhairi; Hammond, Amanda J; Robinson, Robert S

    2012-01-01

    Fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF) A are thought to be key controllers of luteal angiogenesis; however, their precise roles in the regulation and coordination of this complex process remain unknown. Thus, the temporal and spatial patterns of endothelial network formation were determined by culturing mixed cell types from early bovine corpora lutea on fibronectin in the presence of FGF2 and VEGFA (6 h to 9 days). Endothelial cells, as determined by von Willebrand factor immunohistochemistry, initially grew in cell islands (days 0-3), before undergoing a period of vascular sprouting to display a more tubule-like appearance (days 3-6), and after 9 days in culture had formed extensive intricate networks. Mixed populations of luteal cells were treated with SU1498 (VEGF receptor 2 inhibitor) or SU5402 (FGF receptor 1 inhibitor) or control on days 0-3, 3-6 or 6-9 to determine the role of FGF2 and VEGFA during these specific windows. The total area of endothelial cells was unaffected by SU1498 treatment during any window. In contrast, SU5402 treatment caused maximal reduction in the total area of endothelial cell networks on days 3-6 vs controls (mean reduction 81%; P<0.001) during the period of tubule initiation. Moreover, SU5402 treatment on days 3-6 dramatically reduced the total number of branch points (P<0.001) and degree of branching per endothelial cell island (P<0.05) in the absence of changes in mean island area. This suggests that FGF2 is a key determinant of vascular sprouting and hence critical to luteal development.

  16. Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss.

    PubMed

    Stephenson, Mary D; McQueen, Dana; Winter, Michelle; Kliman, Harvey J

    2017-03-01

    To assess the effectiveness of luteal start vaginal micronized P in a recurrent pregnancy loss (RPL) cohort. Observational cohort study using prospectively collected data. Not applicable. Women seen between 2004 and 2012 with a history of two or more unexplained pregnancy losses <10 weeks in size; endometrial biopsy (EB) performed 9-11 days after LH surge; and one or more subsequent pregnancy(ies). Women were excluded if concomitant findings, such as endometritis, maturation delay, or glandular-stromal dyssynchrony, were identified on EB. Vaginal micronized P was prescribed at a dose of 100-200 mg every 12 hours starting 3 days after LH surge (luteal start) if glandular epithelial nuclear cyclin E (nCyclinE) expression was elevated (>20%) in endometrial glands or empirically despite normal nCyclinE (≤20%). Women with normal nCyclinE (≤20%) who did not receive P were used as controls. Pregnancy success was an ongoing pregnancy >10 weeks in size. One hundred sixteen women met the inclusion criteria, of whom 51% (n = 59) had elevated nCyclinE and 49% (n = 57) had normal nCyclinE. Pregnancy success in the 59 women with elevated nCyclinE significantly improved after intervention: 6% (16/255) in prior pregnancies versus 69% (57/83) in subsequent pregnancies. Pregnancy success in subsequent pregnancies was higher in women prescribed vaginal micronized P compared with controls: 68% (86/126) versus 51% (19/37); odds ratio = 2.1 (95% confidence interval, 1.0-4.4). In this study, we found that the use of luteal start vaginal micronized P was associated with improved pregnancy success in a strictly defined cohort of women with RPL. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Simulated conditions of microgravity suppress progesterone production by luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Bhat, G. K.; Yang, H.; Sridaran, R.

    2001-01-01

    The purpose of this study was to assess whether simulated conditions of microgravity induce changes in the production of progesterone by luteal cells of the pregnant rat ovary using an in vitro model system. The microgravity environment was simulated using either a high aspect ratio vessel (HARV) bioreactor with free fall or a clinostat without free fall of cells. A mixed population of luteal cells isolated from the corpora lutea of day 8 pregnant rats was attached to cytodex microcarrier beads (cytodex 3). These anchorage dependent cells were placed in equal numbers in the HARV or a spinner flask control vessel in culture conditions. It was found that HARV significantly reduced the daily production of progesterone from day 1 through day 8 compared to controls. Scanning electron microscopy showed that cells attached to the microcarrier beads throughout the duration of the experiment in both types of culture vessels. Cells cultured in chamber slide flasks and placed in a clinostat yielded similar results when compared to those in the HARV. Also, when they were stained by Oil Red-O for lipid droplets, the clinostat flasks showed a larger number of stained cells compared to control flasks at 48 h. Further, the relative amount of Oil Red-O staining per milligram of protein was found to be higher in the clinostat than in the control cells at 48 h. It is speculated that the increase in the level of lipid content in cells subjected to simulated conditions of microgravity may be due to a disruption in cholesterol transport and/or lesions in the steroidogenic pathway leading to a fall in the synthesis of progesterone. Additionally, the fall in progesterone in simulated conditions of microgravity could be due to apoptosis of luteal cells.

  18. Simulated conditions of microgravity suppress progesterone production by luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Bhat, G. K.; Yang, H.; Sridaran, R.

    2001-01-01

    The purpose of this study was to assess whether simulated conditions of microgravity induce changes in the production of progesterone by luteal cells of the pregnant rat ovary using an in vitro model system. The microgravity environment was simulated using either a high aspect ratio vessel (HARV) bioreactor with free fall or a clinostat without free fall of cells. A mixed population of luteal cells isolated from the corpora lutea of day 8 pregnant rats was attached to cytodex microcarrier beads (cytodex 3). These anchorage dependent cells were placed in equal numbers in the HARV or a spinner flask control vessel in culture conditions. It was found that HARV significantly reduced the daily production of progesterone from day 1 through day 8 compared to controls. Scanning electron microscopy showed that cells attached to the microcarrier beads throughout the duration of the experiment in both types of culture vessels. Cells cultured in chamber slide flasks and placed in a clinostat yielded similar results when compared to those in the HARV. Also, when they were stained by Oil Red-O for lipid droplets, the clinostat flasks showed a larger number of stained cells compared to control flasks at 48 h. Further, the relative amount of Oil Red-O staining per milligram of protein was found to be higher in the clinostat than in the control cells at 48 h. It is speculated that the increase in the level of lipid content in cells subjected to simulated conditions of microgravity may be due to a disruption in cholesterol transport and/or lesions in the steroidogenic pathway leading to a fall in the synthesis of progesterone. Additionally, the fall in progesterone in simulated conditions of microgravity could be due to apoptosis of luteal cells.

  19. Women Ornament Themselves for Intrasexual Competition near Ovulation, but for Intersexual Attraction in Luteal Phase

    PubMed Central

    Zhuang, Jin-Ying; Wang, Jia-Xi

    2014-01-01

    The present study examined women's attentional bias toward ornamental objects in relation to their menstrual phase as well as to motivations of intersexual courtship or intrasexual competition. In Experiment 1, 33 healthy heterosexual women were tested in a bias-assessment visual cuing task twice: once on a high-fertility day (during the ovulatory phase) and once on a low-fertility day (during the luteal phase). They paid greater attention to pictures of ornamental objects than to pictures of non-ornamental objects near ovulation, but not during the luteal phase, suggesting an ornamental bias during the high-fertility phase. In Experiment 2, before the visual cuing task, 40 participants viewed 10 same-sex or opposite-sex facial photographs with either high or low attractiveness as priming tasks to activate the intrasexual competition or intersexual courtship motives. Results showed that women's ornamental bias was dependent on the interaction of menstrual phase and mating motive. Specifically, the ornamental bias was observed on the high-fertility day when the subjects were primed with high-attractive same-sex images (intrasexual competition) and was observed on the low-fertility day when they were primed with high-attractive opposite-sex photographs (intersexual courtship). In conclusion, the present findings confirm the hypothesis that, during the high-fertility phase, women have an attentional bias toward ornamental objects and further support the hypothesis that the ornamental bias is driven by intrasexual competition motivation near ovulation, but driven by intersexual courtship motivation during the luteal phase. PMID:25180577

  20. Natural influence of season on follicular, luteal, and endocrinological turnover in Indian crossbred cows.

    PubMed

    Satheshkumar, S; Brindha, K; Roy, A; Devanathan, T G; Kathiresan, D; Kumanan, K

    2015-07-01

    The study was aimed at investigating the effect of seasonal changes on follicular and luteal dynamics in vivo in normally cycling crossbred cows during summer and winter months of the year. Six healthy regularly cycling Jersey crossbred nonlactating pluriparous cows were used for the study. Follicular and luteal developmental pattern was studied every other day throughout the estrous cycle by scanning the ovaries during two periods of a year viz., hot season (April to June; n = 16) and cold season (December to February; n = 12). Plasma progesterone (P4) concentrations were measured on Days 0 (estrus), 6, and 12 of the estrous cycle. Among the 12 cycles studied during the cold season, 11 (91.7%) had three waves and one had two waves. Of 16 cycles studied during the hot season, eight (50%) had two waves, four (25%) had three waves, and the remaining four cycles had single (n = 2) and four waves (n = 2). High P4 concentrations during the midcycle would have suppressed the dominant follicle of the second follicular wave and induced the emergence of the third wave during the cold season. The first follicular wave (wave I) of the cycle emerged much earlier (Day 0.5 ± 0.3) during the cold season than that in the hot season (Day 1.7 ± 0.4). The ovulatory wave emerged significantly earlier during the hot season (Day 11.5 ± 1.3) than in the cold season (Day 14.8 ± 0.4), and hence, the growth phase of ovulatory follicle significantly increased during the former season (11.0 ± 1.4 days) than the latter (5.8 ± 0.2 days). The ovulatory follicle attained a significantly larger diameter (12.8 ± 0.8 mm) to express the estrus during the hot season when compared to the cold season (11.3 ± 0.4 mm), which might be indicative of alterations in steroidogenic activity within the follicular microenvironment. During the midphase of the cycle, a period critical for embryonic sustenance, the P4 level was significantly reduced in the hot months indicating suppression of luteal activity

  1. Luteal Expression of Thyroid Hormone Receptors During Gestation and Postpartum in the Rat

    PubMed Central

    Navas, Paola B.; Redondo, Analía L.; Cuello-Carrión, F. Darío; Roig, Laura M. Vargas; Valdez, Susana R.; Jahn, Graciela A.

    2014-01-01

    Background: Progesterone (P4) is the main steroid secreted by the corpora lutea (CL) and is required for successful implantation and maintenance of pregnancy. Although adequate circulating levels of thyroid hormone (TH) are needed to support formation and maintenance of CL during pregnancy, TH signaling had not been described in this gland. We determined luteal thyroid hormone receptor isoforms (TR) expression and regulation throughout pregnancy and under the influence of thyroid status, and in vitro effects of triiodothyronine (T3) exposure on luteal P4 synthesis. Methods: Euthyroid female Wistar rats were sacrificed by decapitation on gestational day (G) 5, G10, G15, G19, or G21 of pregnancy or on day 2 postpartum (L2). Hyperthyroidism and hypothyroidism were induced in female Wistar rats by daily administration of thyroxine (T4; 0.25 mg/kg subcutaneously) or 6-propyl-2-thiouracil (PTU; 0.1 g/L in drinking water), respectively. Luteal TR expression of mRNA was determined using real-time reverse-transcription quantitative polymerase chain reaction, and of protein using Western blot and immunohistochemistry. Primary cultures of luteal cells and of luteinized granulosa cells were used to study in vitro effects of T3 on P4 synthesis. In addition, the effect of T3 on P4 synthesis under basal conditions and under stimulation with luteinizing hormone (LH), prolactin (PRL), and prostaglandin E2 (PGE2) was evaluated. Results: TRα1, TRα2, and TRβ1 mRNA were present in CL, increasing during the first half and decreasing during the second half of pregnancy. At the protein level, TRβ1 was abundantly expressed during gestation reaching a peak at G19 and decreasing afterwards. TRα1 was barely expressed during early gestation, peaked at G19, and diminished thereafter. Expression of TRβ1 and TRα1 at the protein and mRNA level were not influenced by thyroid status. T3 neither modified P4 secretion from CL of pregnancy nor its synthesis in luteinized granulosa cells in

  2. [Results' analysis of estradiol and progesterone supplementation in luteal phase vs progesterone alone in an assisted reproduction program].

    PubMed

    Kably Ambe, Alberto; Ruiz Anguas, Julián; Walters Arballo, Fabian; García Benitez, Carlos Quesnel; Karchmer Krivitsky, Samuel

    2005-04-01

    To correlate estradiol and progesterone concentrations in luteal phase with pregnancy rates, and to determine the real value of estradiol administration during luteal phase support. In a prospective and comparative study, 69 patients who underwent IVF-ET program were divided in two groups: group 1 (n = 32) received luteal phase support only with progesterone and group 2, (n = 37) luteal phase support with estradiol and progesterone. Ovarian stimulation was made with recombinant FSH and GnRH analogues (agonists or antagonists) and 24 hours after oocyte retrieval we began luteal phase support: group 1 progesterone (in oily solution) 100 mg/day IM, and group 2 same progesterone doses plus 2 mg of estradiol valerianate. Statistical analysis was performed using students' t- test and ROC curves. No statistical differences were observed in age, preovulatory estradiol levels, oocytes retrieved, fertilization rates, number of embryos transferred, or difficulty of embryo transfer among groups. The overall pregnancy rate was of 34.78% per cycle, no significant differences were observed among groups (37.5 vs 32.43%). We observed greater incidence of miscarriage in group 2 (4.35 vs 0%), without statistical significance. When comparing estradiol levels and pregnancy outcomes, higher levels were observed in the pregnancy group (403.3 vs 221.85 pg/mL) on day 7 post-transfer. Same results were reported for progesterone levels (107.04 vs 240.76). We determined that estradiol levels on day 7, higher than 244 pg/mL, could predict pregnancy with sensitivity of 58% and specificity of 70%, whereas progesterone levels greater than 108.6 ng/mL had specificity and sensitivity of 50 and 70%, respectively. We couldn't determine any advantage with estradiol supplementation during luteal phase support; however, measurement on day 7 of estradiol and progesterone allowed a greater predictive accuracy of pregnancy outcome.

  3. Curcumin inhibits interferon-{alpha} induced NF-{kappa}B and COX-2 in human A549 non-small cell lung cancer cells

    SciTech Connect

    Lee, Jeeyun |; Im, Young-Hyuck | E-mail: imyh@smc.samsung.co.kr; Jung, Hae Hyun; Kim, Joo Hyun; Park, Joon Oh |; Kim, Kihyun |; Kim, Won Seog |; Ahn, Jin Seok

    2005-08-26

    The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-{alpha} treatment. The IFN-{alpha}-treated A549 cells showed increase in protein expression levels of NF-{kappa}B and COX-2. IFN-{alpha} induced NF-{kappa}B binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-{alpha}-induced COX-2 expression in A549 cells. Within 10 min, IFN-{alpha} rapidly induced the binding activity of a {gamma}-{sup 32}P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-{alpha}-induced activations of NF-{kappa}B and COX-2 were inhibited by the addition of curcumin in A549 cells.

  4. Maternal exposure to perfluorooctanoic acid inhibits luteal function via oxidative stress and apoptosis in pregnant mice.

    PubMed

    Chen, Yilu; Zhou, Ling; Xu, Jingjie; Zhang, Lu; Li, Mo; Xie, Xingxing; Xie, Yajuan; Luo, Dan; Zhang, Dalei; Yu, Xiaochun; Yang, Bei; Kuang, Haibin

    2017-04-01

    Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated compound, which has been reported to exert adverse effect on the pregnancy. However, whether it is associated with alteration of luteal function remains unknown. Mice were administered PFOA by gavage from gestational days (GD) 1-7 or 13. PFOA treatment did not significantly affect numbers of embryo implantation. Nevertheless, on GD 13, 10mg/kg PFOA treatment significantly increased numbers of resorbed embryo. Furthermore, PFOA exposure markedly reduced serum progesterone levels but did not affect estradiol levels. Treatment also showed concomitant decreases in transcript levels for key steroidogenic enzymes, and reduced numbers and sizes of corpora lutea. In addition, PFOA administration inhibited activities of superoxide dismutase and catalase, and increased generation of hydrogen peroxide and malondialdehyde, and down-regulated level of Bcl-2 and up-regulated p53 and BAX proteins. In conclusion, PFOA exposure significantly inhibits luteal function via oxidative stress and apoptosis in pregnant mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. 2-bromopalmitate inhibition of stimulatory effect on LH in isolated luteal cells.

    PubMed

    Tan, C H; Robinson, J

    1982-04-05

    The effect of 2-bromopalmitate, an inhibitor of fatty acids oxidation, on progesterone synthesis in isolated luteal cells was studied. Incubation of the cells with increasing concentrations (0 - 2 mM) of the inhibitor resulted in an initial enhancement of progesterone synthesis, both in the presence and absence of LH (1 microgram/ml). In the LH-treated cells, this stimulation in steroid synthesis becomes markedly impaired at 2 mM 2-bromopalmitate. In the control cells, however, progesterone synthesis was sustained at the elevated level. At high concentrations of 2-bromopalmitate, the stimulatory effect of LH (relative to the controls) on steroidogenesis was progressively diminished, until it was completely abolished at an inhibitor concentration of 2 mM. The oxidation of labelled palmitic acid by luteal cells was also effectively inhibited by 2-bromopalmitate (1 mM). The results indicate that the steroidogenic effect of LH is mediated, in part, by fatty acid oxidation, and were explained in terms of the interaction between carbohydrate and fatty acid oxidation in supporting ovarian steroidogenesis.

  6. Relationship between endometritis and oxidative stress in the follicular fluid and luteal function in the buffalo.

    PubMed

    Behera, B K; Sharma, C G; Singh, S K; Kumar, H; Chaudhari, R K; Mahla, A S; Das, G K; Krishnaswamy, N

    2016-10-01

    In this study, alteration in the follicular fluid composition and luteal function was investigated in the buffalo with endometritis. Genitalia were classified into cytological and purulent endometritis on the basis of polymorphonuclear cell cut off while non-endometritis served as control (n = 10/group). In the follicular phase, the number of surface follicles was counted, diameter of the largest follicle was measured and the follicular fluid was assayed for total protein, cholesterol, malondialdehyde (MDA), total antioxidant capacity (TAC), oestradiol (E2 ) and progesterone (P4 ). The P4 content of corpus luteum during mid-luteal phase was estimated by radioimmunoassay. Ovaries from the follicular phase of oestrous cycle showed no significant difference in the total number of surface follicles, size of the largest follicle and volume of follicular fluid in the buffaloes with and without endometritis (p > .05). However, the antral fluid of the largest follicle from the genitalia of buffalo with cytological and purulent endometritis showed a significant decrease in the concentration of total protein, cholesterol, TAC and E2 and a significant increase in the concentration of MDA and P4 (p < .05). The results indicated that there is an association between endometritis and decreased ovarian function.

  7. Tankyrase inhibition regulates corpus luteum development and luteal function in gonadotropin-treated rats.

    PubMed

    Accialini, Paula; Irusta, Griselda; Bechis, Andrés; Bas, Diana; Parborell, Fernanda; Abramovich, Dalhia; Tesone, Marta

    2017-08-01

    Tankyrases are physiological regulators of Axin, a protein involved in several cellular processes, including Wnt signaling. Here, we investigated the effect of a specific Tankyrase inhibitor (XAV939) in follicular-luteal dynamics, and its possible relationship with ovarian vascular development. Studies were designed to analyze the effect of intrabursa administration of XAV939 in gonadotropin-treated prepubertal rats. In particular, we examined follicle and corpus luteum development, steroidogenesis, angiogenic markers, and apoptotic parameters. We found that in vivo inhibition of Wnt signaling impaired corpus luteum development, with a decrease in the number of corpora lutea balanced by a high number of cysts; decreased circulating progesterone levels, likely due to a decrease in Steroidogenic acute regulatory protein content in the corpus luteum; and increased pro-apoptotic parameters. In addition, Extracellular signal-regulated kinase phosphorylation, Vascular endothelium growth factor 120 content, and endothelial cell area were diminished in corpora lutea of inhibitor-treated ovaries. Thus, Wnt/β-catenin signaling appears to participate in the regulation of corpus luteum development and luteal cell function. © 2017 Wiley Periodicals, Inc.

  8. Suppressive effects of antimycotics on tumor necrosis factor-alpha-induced CCL27, CCL2, and CCL5 production in human keratinocytes.

    PubMed

    Kanda, Naoko; Watanabe, Shinichi

    2006-08-14

    Antimycotic agents are reported to improve cutaneous symptoms of atopic dermatitis or psoriasis vulgaris. Keratinocytes in these lesions excessively produce chemokines, CCL27, CCL2, or CCL5 which trigger inflammatory infiltrates. Tumor necrosis factor-alpha (TNF-alpha) induces production of these chemokines via activating nuclear factor-kappaB (NF-kappaB). We examined in vitro effects of antimycotics on TNF-alpha-induced CCL27, CCL2, and CCL5 production in human keratinocytes. Antimycotics ketoconazole and terbinafine hydrochloride suppressed TNF-alpha-induced CCL27, CCL2, and CCL5 secretion and mRNA expression in keratinocytes in parallel to the inhibition of NF-kappaB activity while fluconazole was ineffective. Anti-prostaglandin E2 (PGE2) antiserum or antisense oligonucleotides against PGE2 receptor EP2 or EP3 abrogated inhibitory effects of ketoconazole and terbinafine hydrochloride on TNF-alpha-induced NF-kappaB activity and CCL27, CCL2, and CCL5 production, indicating the involvement of endogenous PGE2 in the inhibitory effects. Prostaglandin H2, a precursor of PGE2 can be converted to thromboxane A2. Ketoconazole, terbinafine hydrochloride and thromboxane A2 synthase (EC 5.3.99.5) inhibitor, carboxyheptyl imidazole increased PGE2 release from keratinocytes and reduced that of thromboxane B2, a stable metabolite of thromboxane A2. Carboxyheptyl imidazole also suppressed TNF-alpha-induced NF-kappaB activity and CCL27, CCL2, and CCL5 production. These results suggest that ketoconazole and terbinafine hydrochloride may suppress TNF-alpha-induced NF-kappaB activity and CCL27, CCL2, and CCL5 production by increasing PGE2 release from keratinocytes. These antimycotics may suppress thromboxane A2 synthesis and redirect the conversion of PGH2 toward PGE2. These antimycotics may alleviate inflammatory infiltration in atopic dermatitis or psoriasis vulgaris by suppressing chemokine production.

  9. Regression: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    Regression, another mechanism studied by Sigmund Freud, has had much research, e.g., hypnotic regression, frustration regression, schizophrenic regression, and infra-human-animal regression (often directly related to fixation). Many investigators worked with hypnotic age regression, which has a long history, going back to Russian reflexologists.…

  10. Regression: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    Regression, another mechanism studied by Sigmund Freud, has had much research, e.g., hypnotic regression, frustration regression, schizophrenic regression, and infra-human-animal regression (often directly related to fixation). Many investigators worked with hypnotic age regression, which has a long history, going back to Russian reflexologists.…

  11. The effect of oxytocin on progesterone secretion, phosphoinositide hydrolysis and intracellular mobilisation of Ca2+ in porcine luteal cells.

    PubMed

    Franczak, Anita; Kurowicka, Beata; Kowalik, Magdalena; Ciereszko, Renata Elzbieta; Kotwica, Genowefa

    2009-03-01

    Oxytocin (OT) is involved in the regulation of steroid secretion by the corpus luteum (CL) in pigs, but OT signal transduction in the porcine CL has not been identified. In this study, the effects of OT on in vitro progesterone (P4) secretion, phosphoinositide (PI) hydrolysis and intracellular mobilisation of Ca2+ ([Ca2+]i) were investigated in porcine luteal cells during the early (days 3-5), mid(days 8-10) and late luteal phases (days 12-14) of the oestrous cycle. Basal concentrations of P4 and accumulation of inositol phosphates (IPs) were higher (P < 0.05) on days 3-5 and 8-10 of the oestrous cycle than on days 12-14. Basal [Ca2+]i mobilisation did not differ among studied periods of the oestrous cycle. Oxytocin (10(-7) M) enhanced P4 secretion and PI hydrolysis (P < 0.05) by luteal cells harvested on days 8-10 of the oestrous cycle. Moreover, OT started to increase mobilisation of [Ca2+]i at the 15th (days 3-5 and 8-10) or 30th second (days 12-14) in porcine luteal cells. It was concluded that in pigs OT acts as a regulator of steroidogenesis, stimulating P4 secretion in mature CL. This OT action may be mediated by changes in PI hydrolysis and [Ca2+]i mobilisation.

  12. Gene expression profiling of bovine ovarian follicular and luteal cells provides insight into cellular identities and functions

    USDA-ARS?s Scientific Manuscript database

    After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

  13. A comparison of ovarian follicular and luteal cell gene expression profiles provides insight into cellular identities and functions

    USDA-ARS?s Scientific Manuscript database

    After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

  14. Effects of follicular versus luteal phase-based strength training in young women.

    PubMed

    Sung, Eunsook; Han, Ahreum; Hinrichs, Timo; Vorgerd, Matthias; Manchado, Carmen; Platen, Petra

    2014-01-01

    Hormonal variations during the menstrual cycle (MC) may influence trainability of strength. We investigated the effects of a follicular phase-based strength training (FT) on muscle strength, muscle volume and microscopic parameters, comparing it to a luteal phase-based training (LT). Eumenorrheic women without oral contraception (OC) (N = 20, age: 25.9 ± 4.5 yr, height: 164.2 ± 5.5 cm, weight: 60.6 ± 7.8 kg) completed strength training on a leg press for three MC, and 9 of them participated in muscle biopsies. One leg had eight training sessions in the follicular phases (FP) and only two sessions in the luteal phases (LP) for follicular phase-based training (FT), while the other leg had eight training sessions in LP and only two sessions in FP for luteal phase-based training (LT). Estradiol (E2), progesterone (P4), total testosterone (T), free testosterone (free T) and DHEA-s were analysed once during FP (around day 11) and once during LP (around day 25). Maximum isometric force (Fmax), muscle diameter (Mdm), muscle fibre composition (No), fibre diameter (Fdm) and cell nuclei-to-fibre ratio (N/F) were analysed before and after the training intervention. T and free T were higher in FP compared to LP prior to the training intervention (P < 0.05). The increase in Fmax after FT was higher compared to LT (P <0.05). FT also showed a higher increase in Mdm than LT (P < 0.05). Moreover, we found significant increases in Fdm of fibre type ΙΙ and in N/F only after FT; however, there was no significant difference from LT. With regard to change in fibre composition, no differences were observed between FT and LT. FT showed a higher gain in muscle strength and muscle diameter than LT. As a result, we recommend that eumenorrheic females without OC should base the periodization of their strength training on their individual MC.

  15. [Luteal insufficicency in the bitch - symptoms, diagnosis, consequences and therapy. A review of the literature].

    PubMed

    Becher, A; Wehrend, A; Goericke-Pesch, S

    2010-01-01

    Insufficient progesterone synthesis, so called hypoluteoidism or luteal insufficiency, is one of the possible reasons for infertility in the bitch. Confirming this diagnosis may be difficult if the dynamic changes of progesterone during the reproductive cycle are not taken into account. The bitch ovulates at progesterone concentrations of about 5-10ng/ml (15.7-31.4 nmol/L). The concentrations increase to >25ng/mL (78.5 nmol/L) within 3-4 weeks and then subsequently decrease after a plateau of 7-14 days. In the pregnant bitch, progesterone rapidly drops to <2ng/ml (6.3 nmol/L) approximately 24-48 hours before parturition induced by PGF2α secretion. Luteal insufficiency, characterized as an early decrease of progesterone secretion, is most commonly observed between days 20 and 35 of pregnancy. Progesterone concentrations of approximately 2ng/ml (6.3nmol/L) are thought to be necessary for maintaining pregnancy. Lower concentrations result in resorption and abortion, respectively. In bitches suspected to have luteal insufficiency, weekly progesterone determinations using quantitative tests should be performed from 5-7 days after mating or at least from the date of early pregnancy diagnosis. The frequency has to be increased in the case of progesterone concentrations below 10ng/ml (31.4 nmol/L). Progesterone administration is indicated in the case of viable foetuses and progesterone concentrations <5 ng/ml (15.7 nmol/L) before day 58/60 of pregnancy or after the detection of a rapid progesterone decline of about 10-15ng/ml (31.4-47.1 nmol/L) between days 20 and 35 with viable foetuses in the sonographic examination. Either natural or synthetic progestins can be used. However, synthetic progestins have a greater risk potential for side effects (masculinisation of female puppies and cryptorchidism in male puppies), especially when administered between days 20 and 35 of pregnancy. Administration of natural progesterone should be stopped 2-3 days before expected

  16. Dual regulation of luteal progesterone production by androstenedione during spontaneous and RU486-induced luteolysis in pregnant rats.

    PubMed

    Tellería, C M; Stocco, C O; Stati, A O; Rastrilla, A M; Carrizo, D G; Aguado, L I; Deis, R P

    1995-12-01

    The effect of androstenedione on luteal progesterone production was studied during luteolysis preceding parturition as well as that induced by the antiprogestin RU486 in late pregnant rats. Luteal cells from animals on days 19, 20 or 21 of pregnancy and incubated with 10 microM androstenedione increased progesterone production by 99, 136, and 277%, respectively. The animals receiving androstenedione (10 mg/rat s.c.) on day 19 of pregnancy showed an increase in serum progesterone levels, a decline in luteal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity and an increase in corpus luteum weight without modifying 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity on day 21 of pregnancy. Androstenedione and testosterone but not dihydrotestosterone were able to prevent the decrease in serum progesterone concentration and corpus luteum weight observed 58 h after treatment with RU486 (2 mg/kg) on day 18 of pregnancy. However, the three androgens studied inhibited the luteal 3 beta-HSD activity but 20 alpha-HSD activity was not affected, when compared with animals receiving RU486 alone. The co-administration of androstenedione with the aromatase inhibitor 4-hydroxyandrostenedione or with the specific antioestrogen ICI 164,384 did not modify the effects induced by androstenedione in RU486-treated rats, indicating that the action of androstenedione on progesterone production and secretion at the time of luteolysis seems to occur through an androgenic mechanism and is not mediated by previous conversion of the androgens to oestrogens. In all experiments the high luteal 20 alpha-HSD activity, that characterizes a luteolytic process, was not modified by androgens. Androstenedione administered to adrenalectomized rats was also able to prevent the decrease in serum progesterone concentration observed in spontaneous or RU486-induced luteolysis. The administration of androstenedione to RU486-treated rats induced a decrease in luteal progesterone content

  17. Measurement of plasma human chorionic gonadotropin (hCG) and beta-hCG activities in the late luteal phase: evidence of the occurrence of spontaneous menstrual abortions in infertile women.

    PubMed

    Chartier, M; Roger, M; Barrat, J; Michelon, B

    1979-02-01

    Plasma luteinizing hormone (LH-human chorionic gonadotropin (hCG) and beta-hCG activities were measured during the late luteal phase in 321 cycles of 147 infertile women. In 71 cycles the hCG measurement permitted the diagnosis of pregnancy between the 10th and 14th days after the thermal nadir. The slope of the regression line derived from hCG levels during the first 22 days of pregnancy was significantly lower in pregnancies which aborted before the 60th day than in normal pregnancies (P less than 0.01). Among 72 cycles ended by apparently normal menses which exhibited an LH-hCG activity at least equal to 7 mIU of hCG/ml during the late luteal phase, the beta-hCG activity was measured in 49 cycles during which hCG had not been given. Significant beta-hCG activity (greater than or equal to 4 mIU of hCG/ml) was detected in 19 cases. This finding supports the assumption that secretory trophoblastic tissue had been present and that spontaneous menstrual abortions had occurred in these women.

  18. GnRH agonist trigger with intensive luteal phase support vs. human chorionic gonadotropin trigger in high responders: an observational study reporting pregnancy outcomes and incidence of ovarian hyperstimulation syndrome.

    PubMed

    Christopoulos, Georgios; Vlismas, Antonios; Carby, Anna; Lavery, Stuart; Trew, Geoffrey

    2016-09-01

    A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had ≥18 follicles ≥11mm or serum oestradiol >18,000pmol/l on the day of trigger. Patients had a single or double embryo transfer at cleavage or blastocyst stage. Logistic regression was used to adjust for differences between the groups. An intention-to-treat analysis of all cycles was performed. No statistically significant differences were observed in terms of positive pregnancy test, clinical pregnancy rate and live birth rate. Only one patient (0.3%) was hospitalized with severe OHSS in the GnRHa group, compared to 26 patients (13%) in the hCG group. In conclusion, GnRHa trigger is associated with similar pregnancy rates with hCG trigger and a significant reduction in hospitalization for severe OHSS after an intention to treat analysis was performed.

  19. Ginsenosides compound K and Rh(2) inhibit tumor necrosis factor-alpha-induced activation of the NF-kappaB and JNK pathways in human astroglial cells.

    PubMed

    Choi, Kyungsun; Kim, Myungsun; Ryu, Jeonghee; Choi, Chulhee

    2007-06-21

    Ginsenosides, the main component of Panax ginseng, have been known for the anti-inflammatory and anti-proliferative activities. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory effects of ginsenosides on activated astroglial cells. Among 13 different ginsenosides, intestinal bacterial metabolites Rh(2) and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh(2) exert anti-inflammatory effects by the inhibition of both NF-kappaB and JNK pathways in a cell-specific manner.

  20. Wogonin suppresses TNF-{alpha}-induced MMP-9 expression by blocking the NF-{kappa}B activation via MAPK signaling pathways in human aortic smooth muscle cells

    SciTech Connect

    Lee, Syng-Ook; Jeong, Yun-Jeong; Yu, Mi Hee; Lee, Ji-Won; Hwangbo, Mi Hyang; Kim, Cheorl-Ho; Lee, In-Seon . E-mail: inseon@kmu.ac.kr

    2006-12-08

    Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-{alpha}-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-{alpha}-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-{kappa}B via MAPK signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-{alpha}-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-{alpha}-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.

  1. Localized accumulation of angiotensin II and production of angiotensin-(1-7) in rat luteal cells and effects on steroidogenesis.

    PubMed

    Pepperell, John R; Nemeth, Gabor; Yamada, Yuji; Naftolin, Frederick; Merino, Maricruz

    2006-08-01

    These studies aim to investigate subcellular distribution of angiotensin II (ANG II) in rat luteal cells, identify other bioactive angiotensin peptides, and investigate a role for angiotensin peptides in luteal steroidogenesis. Confocal microscopy showed ANG II distributed within the cytoplasm and nuclei of luteal cells. HPLC analysis showed peaks that eluted with the same retention times as ANG-(1-7), ANG II, and ANG III. Their relative concentrations were ANG II >or= ANG-(1-7) > ANG III, and accumulation was modulated by quinapril, an inhibitor of angiotensin-converting enzyme (ACE), Z-proprolinal (ZPP), an inhibitor of prolyl endopeptidase (PEP), and parachloromercurylsulfonic acid (PCMS), an inhibitor of sulfhydryl protease. Phenylmethylsulfonyl fluoride (PMSF), a serine protease inhibitor, did not affect peptide accumulation. Quinapril, ZPP, PCMS, and PMSF, as well as losartan and PD-123319, the angiotensin receptor type 1 (AT1) and type 2 (AT2) receptor antagonists, were used in progesterone production studies. ZPP significantly reduced luteinizing hormone (LH)-dependent progesterone production (P < 0.05). Quinapril plus ZPP had a greater inhibitory effect on LH-stimulated progesterone than either inhibitor alone, but this was not reversed by exogenous ANG II or ANG-(1-7). Both PCMS and PMSF acutely blocked LH-stimulated progesterone, and PCMS blocked LH-sensitive cAMP accumulation. Losartan inhibited progesterone production in permeabilized but not intact luteal cells and was reversed by ANG II. PD-123319 had no significant effect on luteal progesterone production in either intact or permeabilized cells. These data suggest that steroidogenesis may be modulated by angiotensin peptides that act in part through intracellular AT1 receptors.

  2. Endocrine disruptors and human reproductive failure: the in vitro effect of phthalates on human luteal cells.

    PubMed

    Romani, Federica; Tropea, Anna; Scarinci, Elisa; Federico, Alex; Dello Russo, Cinzia; Lisi, Lucia; Catino, Stefania; Lanzone, Antonio; Apa, Rosanna

    2014-09-01

    To evaluate the influence of phthalates on human luteal cell function. Laboratory study. University hospital. Twenty-three normally menstruating patients in the midluteal phase. Human luteal cells isolated from corpora lutea for primary cultures. Progesterone (P4) and prostaglandin release assayed by enzyme immunoassay, vascular endothelial growth factor (VEGF) secretion by enzyme-linked immunosorbent assay (ELISA), and VEGF mRNA expression by real-time polymerase chain reaction. We investigated the effect of di(2-ethylhexyl)phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) on basal and hCG-induced progesterone (P4) release, as well as DEHP effect on the balance between prostaglandin (PG) E2, vascular endothelial growth factor (VEGF)-luteotrophic factors, and the luteolitic PGF2α in isolated human steroidogenc cells. Phthalates influence on VEGF expression has been also evaluated. DEHP, DBP, and BBP were able to reduce both basal and hCG-stimulated P4 as well as PGE2 release. PGF2α release was reduced after DEHP incubation. VEGF protein release was decreased by the incubation with the tested phthalates. VEGF mRNA expression was not affected by DEHP, DBP, and BBP. As expected, both hCG and cobalt chloride were able to induce P4 release and VEGF release and mRNA expression in human luteal cells respectively. The results show the ability of phthalates to affect luteal steroidogenesis as well as the balance between luteotrophic and luteolytic factors suggesting an interference of phthalates in human luteal function. These data may contribute to clarify the classically known impaired reproductive health observed after phthalates exposure. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Internalization and degradation of human chorionic gonadotropin in ovine luteal cells: Kinetic studies

    SciTech Connect

    Ahmed, C.E.; Sawyer, H.R.; Niswender, G.D.

    1981-11-01

    Ovine luteal cells grown in suspensions and/or monolayer culture were used to study the rates of internalization and degradation of (/sup 125/I)hCG. At specified times after a 5- to 7-min exposure to (/sup 125/I)hCG, cells were treated with acidic buffer (pH 3.9) to elute membrane-bound hormone, which left the internalized radioactivity associated with the cell pellet. Radioactivity released into the medium during the incubation periods was subjected to 20% trichloroacetic acid and/or thin layer chromatography to monitor the extent of degradation of the radioactive hormone. Secretion of progesterone into the medium and exclusion of trypan blue were used to monitor the viability of the cells in each experiment. Radioactivity was lost from the plasma membrane with a tsub1/2 of 9.6 h, with approximately 85% of the radioactivity being lost within 24 h. Cell-associated radioactivity increased linearly with time to a plateau at 4 h, remained stable until 12 h, and then decreased between 12-24 h. The plateau between 4-12 h reflected an equilibrium between the (/sup 125/I)hCG which was internalized and degraded and the (/sup 125/I)hCG which was released into the medium. The degraded (/sup 125/I)hCG increased essentially linearly up to 24 h. These data suggest that the majority of (/sup 125/I)hCG bound to receptors in luteal cells is internalized and degraded. Less than 20% of the radioactivity bound initially to cells dissociated into the incubation medium and was trichloroacetic acid precipitable within 24 h. The internalization and degradation of (/sup 125/I)hCG was temperature dependent, with essentially no hCG internalized and/or degraded at 4C.

  4. Blunted Myoglobin and Quadriceps Soreness After Electrical Stimulation During the Luteal Phase or Oral Contraception.

    PubMed

    Anderson, Lindsey J; Baker, Lucinda L; Schroeder, E Todd

    2017-06-01

    Acute muscle damage after exercise triggers subsequent regeneration, leading to hypertrophy and increased strength after repeated exercise. It has been debated whether acute exercise-induced muscle damage is altered under various premenopausal estrogen conditions. Acute contraction-induced muscle damage was compared during exogenous (oral contraceptive, OC), endogenous (luteal phase, HI), or low (menses, LO) estrogen in healthy young women aged 21 to 30 years old. Women (OC, n = 9; HI, n = 9; LO, n = 8; total N = 26) performed 1 neuromuscular electrical stimulation (NMES) bout. Soreness, measured via visual analog scale and the Likert Scale of Muscle Soreness for Lower Limb (LSMSLL), quadriceps strength, and plasma myoglobin (Mb), interleukin (IL)-6, IL-8, and granulocyte-colony stimulating factor were measured before and after NMES. NMES performance was similar across groups. Meaningful within-group increases in Mb (effect size [ES] = 1.12) and IL-8 (ES = 0.38) occurred in LO; ES for HI and OC were trivial. ES of the between-group difference in change was moderate for Mb (LO vs. HI = 1.15) and IL-8 (LO vs. HI = 0.86; LO vs. OC = 0.73). 17-β estradiol correlated moderately and negatively with Mb relative change (r = -.52, p < .05). LO had ~5% greater strength loss than OC and HI. The mean change score for the LSMSLL 2 days post-NMES was clinically greater in LO than OC or HI. Acute NMES-induced indicators of muscle fiber damage and qualitative muscle soreness may be attenuated during the luteal phase or active OC pill consumption compared with the menstrual phase.

  5. Circadian Variation of Sleep During the Follicular and Luteal Phases of the Menstrual Cycle

    PubMed Central

    Shechter, Ari; Varin, France; Boivin, Diane B.

    2010-01-01

    Study Objectives: Women experience insomnia more frequently than men. Menstrual cycle changes in reproductive hormones and circadian rhythms may contribute to sleep disruptions. Our aim, therefore, was to clarify the interaction between menstrual and circadian processes as it affects sleep. Design: Participants entered the laboratory during the mid-follicular (MF) and mid-luteal (ML) phases of their menstrual cycle for an ultra-rapid sleep-wake cycle (URSW) procedure, consisting of 36 cycles of 60-min wake episodes alternating with 60-min nap opportunities. This procedure concluded with an ad libitum nap episode. Setting: Time-isolation suite. Participants: Eight unmedicated, physically and mentally healthy females with regular ovulatory menstrual cycles. Interventions: N/A Measurements: Polysomnographic sleep from nocturnal sleep episodes and 60-min naps; subjective alertness; core body temperature (CBT); salivary melatonin; urinary estradiol; and urinary progesterone. Results: Increased CBT values at night and decreased CBT amplitude were observed during ML compared to MF. Circadian phase of CBT and the circadian melatonin profile were unaffected by menstrual phase. All analyzed sleep parameters showed a circadian variation throughout the URSW procedure, with no menstrual phase differences observed for most, including slow wave sleep (SWS). The circadian variation of REM sleep duration, however, was sensitive to menstrual phase, with reduced REM sleep during ML at circadian phase 0° and 30°. Conclusions: Moderate but significant changes in REM sleep across the menstrual and circadian cycles were observed. These results support an interaction between circadian and menstrual processes in the regulation of REM sleep. Citation: Shechter A; Varin F; Boivin DB. Circadian variation of sleep during the follicular and luteal phases of the menstrual cycle. SLEEP 2010;33(5):647-656. PMID:20469807

  6. Ridge Regression: A Panacea?

    ERIC Educational Resources Information Center

    Walton, Joseph M.; And Others

    1978-01-01

    Ridge regression is an approach to the problem of large standard errors of regression estimates of intercorrelated regressors. The effect of ridge regression on the estimated squared multiple correlation coefficient is discussed and illustrated. (JKS)

  7. Expression and contribution of the HIF-1α/VEGF signaling pathway to luteal development and function in pregnant rats.

    PubMed

    Wu, Lixiang; Zhang, Zhenghong; Pan, Xiaoyan; Wang, Zhengchao

    2015-11-01

    Vascular endothelial growth factor (VEGF) is vital in normal and abnormal angiogenesis in the ovary, particularly during the early development of the corpus luteum in the ovary. However, the molecular regulation of the expression VEGF during luteal development in vivo remains to be fully elucidated. As the expression of VEGF is mediated by hypoxia‑inducible factor (HIF)‑1α in luteal cells cultured in vitro, determined in our previous study, the present study was performed to confirm the hypothesis that HIF‑1α is induced and then regulates the expression of VEGF and VEGF‑dependent luteal development/function in vivo. This was investigated using a pregnant rat model treated with a small‑molecule inhibitor of HIF‑1α, echinomycin (Ech). The development of the corpus luteum in the pregnant rat ovary was identified via performing assays of the serum progesterone, testosterone and estradiol concentrations by radioimmunoassay, accompanied with determination of the changes in the expression levels of HIF‑1α and VEGF by reverse transcription‑quantitative polymerase chain reaction at different days of the developmental process. On day 5, serum progesterone levels were markedly increased, whereas serum levels of testosterone and estradiol did not change significantly. On day 17, the highest level of serum progesterone was observed, however, this was not the case for testosterone and estradiol. Further analysis of the expression levels of HIF‑1α and VEGF revealed that their changes were consistent with the changes in serum levels of progesterone, which occurred in the development of the corpus luteum in the ovaries of pregnant rats. Further investigation demonstrated that Ech inhibited luteal development through inhibiting the expression of VEGF, mediated by HIF‑1α, and subsequent luteal function, which was determined by detecting changes in serum progesterone on days 8 and 14. Taken together, these results demonstrated that HIF‑1

  8. Inhibition of TNF-alpha induced cell death in human umbilical vein endothelial cells and Jurkat cells by protocatechuic acid.

    PubMed

    Zhou-Stache, J; Buettner, R; Artmann, G; Mittermayer, C; Bosserhoff, A K

    2002-11-01

    The Chinese herb radix Salviae miltiorrhizae (RSM) is used in traditional Chinese medicine as a treatment for cardiovascular and cerebrovascular diseases. Several components of the plant extract from salvia mitorrhiza bunge have been determined previously, one of which is protocatechuic acid (PAC). It has been found, in the study, that PAC inhibited TNF-alpha-induced cell death of human umbilical vein endothelial cells (HUVECs) and Jurkat cells in a concentration of 100 microM when applied 2 h prior to TNF-alpha exposure. Molecular studies revealed that PAC activated NF-kappaB with a maximum effect after 30 min of treatment. Inhibition of NF-kappaB action by MG132 and NF-kappaB inhibitory peptide suppressed the cell-protective effect of PAC. Further, degradation of IkBalpha occurred in response to PAC treatment. The results provide evidence that activation of NF-kappaB plays an important role in mediating the cell-protecting effect of PAC on HUVECs and Jurkat cells. Further studies are required to test whether PAC, a component of radix salviae miltiorrhizae, could be useful in preventing in vivo cell death resulting from cardiovascular or cerebrovascular diseases.

  9. Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1

    PubMed Central

    2013-01-01

    Background Tumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues. Results In present study, we provide evidence that TIPE2 inhibits effectively human hepatocellular carcinoma metastasis. The forced expression of TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration and invasion in vitro and suppresses growth and metastasis of HCC in vivo. Clinical information from a cohort of 112 patients reveals that loss or reduced expression of TIPE2 in primary HCC tissues is significantly associated with tumor metastasis. Mechanically, TIPE2 inhibits the migration and invasion through targeting Rac1 and then reduces F-actin polymerization and expression of matrix metallopeptidase 9 (MMP9) and urokinase plasminogen activator (uPA). Conclusion Our results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2 will be a new target for HCC therapy. PMID:24274578

  10. Involvement of phosphatidylinositol 3-kinase in stromal cell-derived factor-1 alpha-induced lymphocyte polarization and chemotaxis.

    PubMed

    Vicente-Manzanares, M; Rey, M; Jones, D R; Sancho, D; Mellado, M; Rodriguez-Frade, J M; del Pozo, M A; Yáñez-Mó, M; de Ana, A M; Martínez-A, C; Mérida, I; Sánchez-Madrid, F

    1999-10-01

    The role of phosphatidylinositol 3-kinase (PI3-kinase), an important enzyme involved in signal transduction events, has been studied in the polarization and chemotaxis of lymphocytes induced by the chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha). This chemokine was able to directly activate p85/p110 PI3-kinase in whole human PBL and to induce the association of PI3-kinase to the SDF-1 alpha receptor, CXCR4, in a pertussis toxin-sensitive manner. Two unrelated chemical inhibitors of PI3-kinase, wortmannin and Ly294002, prevented ICAM-3 and ERM protein moesin polarization as well as the chemotaxis of PBL in response to SDF-1 alpha. However, they did not interfere with the reorganization of either tubulin or the actin cytoskeleton. Moreover, the transient expression of a dominant negative form of the PI3-kinase 85-kDa regulatory subunit in the constitutively polarized Peer T cell line inhibited ICAM-3 polarization and markedly reduced SDF-1 alpha-induced chemotaxis. Conversely, overexpression of a constitutively activated mutant of the PI3-kinase 110-kDa catalytic subunit in the round-shaped PM-1 T cell line induced ICAM-3 polarization. These results underline the role of PI3-kinase in the regulation of lymphocyte polarization and motility and indicate that PI3-kinase plays a selective role in the regulation of adhesion and ERM proteins redistribution in the plasma membrane of lymphocytes.

  11. TNF-alpha-induced apoptosis is prevented by erythropoietin treatment on SH-SY5Y cells

    SciTech Connect

    Pregi, Nicolas Wenker, Shirley; Vittori, Daniela; Leiros, Claudia Perez; Nesse, Alcira

    2009-02-01

    The growth factor erythropoietin (Epo) has shown neuronal protective action in addition to its well known proerythroid activity. Furthermore, Epo has dealt with cellular inflammation by inhibiting the expression of several proinflammatory cytokines, such as IL-1 and TNF-{alpha}. The action of TNF can have both apoptotic and antiapoptotic consequences due to altered balance between different cell signalling pathways. This work has focused on the apoptotic effects of this cytokine and the potential protective action of Epo. The model we used was neuroblastoma SH-SY5Y cells cultured in the presence of 25 ng/ml TNF-{alpha} or pretreated with 25 U/ml Epo for 12 h before the addition of TNF-{alpha}. Apoptosis was evaluated by differential cell count after Hoechst staining, analysis of DNA ladder pattern, and measurement of caspase activity. Despite its ability to induce NF-{kappa}B nuclear translocation, TNF-{alpha} induced cell death, which was found to be associated to upregulation of TNF Receptor 1 expression. On the other hand, cells activated by Epo became resistant to cell death. Prevention of death receptor upregulation and caspase activation may explain this antiapoptotic effect of Epo, which may be also favoured by the induction of a higher expression of protective factors, such as Bcl-2 and NF-{kappa}B, through mechanisms involving Jak/STAT and PI3K signalling pathways.

  12. FSH up-regulates angiogenic factors in luteal cells of buffaloes.

    PubMed

    Fátima, L A; Evangelista, M C; Silva, R S; Cardoso, A P M; Baruselli, P S; Papa, P C

    2013-11-01

    Follicle-stimulating hormone has been widely used to induce superovulation in buffaloes and cows and usually triggers functional and morphologic alterations in the corpus luteum (CL). Several studies have shown that FSH is involved in regulating vascular development and that adequate angiogenesis is essential for normal luteal development. Angiogenesis is regulated by many growth factors, of which vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) have an established central role. Therefore, we have used a combination of in vitro and in vivo studies to assess the effects of FSH on the expression of VEGF and FGF2 and their receptors in buffalo luteal cells. The in vivo model consisted of 12 buffalo cows, divided into control (n = 6) and superovulated (n = 6) groups, and CL samples were collected on day 6 after ovulation. In this model, we analyzed the gene and protein expression of FGF2 and its receptors and the protein expression of VEGFA systems with the use of real-time PCR, Western blot analysis, and immunohistochemistry. In the in vitro model, granulosa cells were collected from small follicles (diameter, 4-6 mm) of buffaloes and cultured for 4 d in serum-free medium with or without FSH (10 ng/mL). To induce in vitro luteinization, LH (250 ng/mL) and fetal bovine serum (10%) were added to the medium, and granulosa cells were maintained in culture for 4 d more. The progesterone concentration in the medium was measured at days 4, 5, and 8 after the beginning of cell culture. Cells were collected at day 8 and subjected to real-time PCR, Western blot analysis, and immunofluorescence for assessment of the expression of FGF2, VEGF, and their receptors. To address the percentage of steroidogenic and growth factor-expressing cells in the culture, flow cytometry was performed. We observed that in superovulated buffalo CL, the FGF2 system mRNA expression was decreased even as protein expression was increased and that the VEGF protein was

  13. The effect of luteal phase gonadotropin-releasing hormone antagonist administration on IVF outcomes in women at risk of OHSS

    PubMed Central

    Eftekhar, Maryam; Miraj, Sepideh; Mortazavifar, Zahrasadat

    2016-01-01

    Background: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. Objective: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. Materials and Methods: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included. Sixty-seven patients (group I) received Cetrorelix 0.25 mg/daily in the luteal phase for 3 days while in 27 participants (group II), it was not administered. Pregnancy outcomes were assessed based on chemical and clinical pregnancy rates. Results: The pregnancy outcomes were not significantly different between two groups (p=0.224). Conclusion: The present study proposed that luteal phase GnRH antagonist administration does not influence the chance of successful pregnancy outcomes. PMID:27679825

  14. Impact of GnRH agonist triggering and intensive luteal steroid support on live-birth rates and ovarian hyperstimulation syndrome: a retrospective cohort study.

    PubMed

    Iliodromiti, Stamatina; Lan, Vuong Thi Ngoc; Tuong, Ho Manh; Tuan, Phung Huy; Humaidan, Peter; Nelson, Scott M

    2013-12-26

    Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory implantation rates can be sustained. The objective of this study was to assess the live-birth rate and incidence of OHSS after GnRHa trigger and intensive luteal steroid support compared to traditional hCG trigger and conventional luteal support in OHSS high risk Asian patients. We conducted a retrospective cohort study of 363 women exposed to GnRHa triggering with intensive luteal support compared with 257 women exposed to conventional hCG triggering. Women at risk of OHSS were defined by ovarian response ≥15 follicles ≥12 mm on the day of the trigger. Live-birth rates were similar in both groups GnRHa vs hCG; 29.8% vs 29.2% (p = 0.69). One late onset severe OHSS case was observed in the GnRHa trigger group (0.3%) compared to 18 cases (7%) after hCG trigger. GnRHa trigger combined with intensive luteal steroid support in this group of OHSS high risk Asian patients can facilitate fresh embryo transfer, however, in contrast to previous reports the occurrence of late onset OHSS was not completely eliminated.

  15. Efficacy of a single injection of human chorionic gonadotropin at peak follicular maturation in natural cycles on pregnancy rate and mid-luteal hormonal and sonographic parameters.

    PubMed

    Check, J H; Liss, J R; DiAntonio, G; Summers, D

    2016-01-01

    To discover if infertile women with presumed luteal phase deficiency would improve pregnancy rates, mid-luteal sera estradiol (E2) and progesterone (P), and increase the percentage of women achieving a mid-luteal sonographic homogeneous hyperechogenic endometrial texture by the addition of a single injection of human chorionic gonadotropin (hCG). Women with over one year of infertility with regular menses and with no other known infertility factor were presumed to have the need for extra P in the luteal phase based on previous studies. Women aged ≥ 30 years were selected along with women < 30 years who had pelvic pain or dysmenorrhea. Women aged 40-45 were evaluated separately. They were treated with either vaginal micronized P 8% twice daily alone or 10,000 units of hCG at the time of peak follicular maturation was also given. Women were eliminated if they did not achieve an 18-24 average diameter follicle with a serum E2 of > 200 pg/ml. Seven days after ovulation, sera E2 and P were measured along with endometrial thickness and echo patterns. The only significant difference between groups was an increased mid-luteal serum E2 in the group receiving additional hCG. However, this did not result in an increased pregnancy rate. In general, adding a single injection of hCG to P luteal support does not improve pregnancy rates in natural cycles where women were treated with supplemental P.

  16. Different processing of LH/hCG receptors in cultured rat luteal cells and murine Leydig tumor cells (MLTC-1)

    SciTech Connect

    Kellokumpu, S.

    1987-02-01

    The metabolic fate of LH/hCG receptors after exposure to human chorionic gonadotropin (hCG) was examined in cultured rat luteal cells and murine Leydig tumor cells (MLTC-1). Kinetic studies performed after pulse-labelling of the cells with (/sup 125/I)hCG indicated that the bound hormone was lost much more rapidly from the tumor cells than from the luteal cells. The tumor cells were also found to internalize and degrade the hormone more effectively than the luteal cells. Chemical cross-linking and analyses by SDS-PAGE of this material revealed that both cell types also released, in addition to intact hCG, two previously characterized receptor fragment-(/sup 125/I)hCG complexes (M/sub r/ 96,000 and 74,000) into the medium, although their amount was negligible in MLTC-1 cells. Possibly due to rapid discharge of the ligand from its receptor, no similar complexes could be detected inside the MLTC-1 cells, suggesting that they were released directly from the cell surface. However, the M/sub r/ 74,000 complex was observed inside MLTC-1 cells if chloroquine, a lysosomotropic agent, was present during the incubations. This suggests that the internalized receptor also becomes degraded, at least when complexed to hCG. The results thus provide evidence that there exist two different mechanisms for proteolytic processing of LH/hCG receptors in these target cells. In tumor cells, the degradation seems to occur almost exclusively intracellularly, whereas in luteal cells a substantial portion of the receptors is also degraded at the cell surface.

  17. Patients' administration preferences: progesterone vaginal insert (Endometrin®) compared to intramuscular progesterone for Luteal phase support.

    PubMed

    Beltsos, Angeline N; Sanchez, Mark D; Doody, Kevin J; Bush, Mark R; Domar, Alice D; Collins, Michael G

    2014-11-11

    Administration of exogenous progesterone for luteal phase support has become a standard of practice. Intramuscular (IM) injections of progesterone in oil (PIO) and vaginal administration of progesterone are the primary routes of administration. This report describes the administration preferences expressed by women with infertility that were given progesterone vaginal insert (PVI) or progesterone in oil injections (PIO) for luteal phase support during fresh IVF cycles. A questionnaire to assess the tolerability, convenience, and ease of administration of PVI and PIO given for luteal phase support was completed by infertile women diagnosed with PCOS and planning to undergo IVF. The women participated in an open-label study of highly purified human menopausal gonadotropins (HP-hMG) compared with recombinant FSH (rFSH) given for stimulation of ovulation. Most women commented on the convenience and ease of administration of PVI, while a majority of women who administered IM PIO described experiencing pain. In addition, their partners often indicated that they had experienced at least some anxiety regarding the administration of PIO. The most distinguishing difference between PVI and PIO in this study was the overall patient preference for PVI. Despite the need to administer PVI either twice a day or three times a day, 82.6% of the patients in the PVI group found it "very" or "somewhat convenient" compared with 44.9% of women in the PIO group. The results of this comprehensive, prospective patient survey, along with findings from other similar reports, suggest that PVI provides an easy-to-use and convenient method for providing the necessary luteal phase support for IVF cycles without the pain and inconvenience of daily IM PIO. Moreover, ongoing pregnancy rates with the well-tolerated PVI were as good as the pregnancy rates with PIO. ClinicalTrial.gov, NCT00805935.

  18. [Preliminary report of the treatment of luteal phase defect by replenishing kidney. An analysis of 53 cases].

    PubMed

    Zhang, H Y; Yu, X Z; Wang, G L

    1992-08-01

    53 patients with Luteal phase defect (LPD) were treated with different Chinese medicinal herbs at different phases of menstrual cycle. On the 5th day of the menstrual cycle, the treatment was implemented with the rationale of "nourishing the Kidney Yin, invigorating the Spleen and replenishing the Qi, promoting the blood circulation and enriching the Blood" which might promote follicular development. The principle for the postovulatory treatment was that "invigorating the Kidney and strengthening the Yang" might enhance the development of corpus luteum and maintain its function. The patients were treated for three menstrual cycles. There were significant improvement in the luteal phase of endometrium, and prolonged basal body temperature elevation in progestational stage with a tendency for normalization of the wave forms and its amplitude after the treatment. In the mid-progestational stage, the level of serum LH and PRL were reduced (P < 0.05) and that of serum progestin (P) rose significantly (P < 0.01), as compared with those before the treatment. The findings suggested that Chinese herbal medicines capable of replenishing the Kidney could regulate the hypothalamus-pituitary-ovarian axis and thus improve the luteal function. Among the 53 cases, 22 (41.5%) conceived but 68.18% of them required other measures to preserve the pregnancy.

  19. Luteal phase supplementation after gonadotropin-releasing hormone agonist trigger in fresh embryo transfer: the American versus European approaches.

    PubMed

    Humaidan, Peter; Engmann, Lawrence; Benadiva, Claudio

    2015-04-01

    The challenges in attaining an adequate luteal phase after GnRH agonist (GnRHa) trigger to induce final oocyte maturation have resulted in different approaches focused on rescuing the luteal phase insufficiency so that a fresh transfer can be carried out without jeopardizing IVF outcomes. Over the years, two different concepts have emerged: intensive luteal support with aggressive exogenous administration of E2 and P; and low-dose hCG rescue in the form of a small dose of hCG either on the day of oocyte retrieva or on the day of GnRHa trigger (the so called "dual trigger"). Both approaches have been shown to be effective in achieving pregnancy rates similar to those obtained after conventional hCG trigger and resulting in a very low risk of ovarian hyperstimulation syndrome (OHSS). Although the idea of freezing all embryos after GnRHa trigger and transferring them in a subsequent frozen-thawed cycle has been gaining momentum, a fresh transfer leading to the live birth of a healthy child is currently considered to be the goal of IVF treatment. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Progesterone luteal support after ovulation induction and intrauterine insemination: an updated systematic review and meta-analysis.

    PubMed

    Green, Katherine A; Zolton, Jessica R; Schermerhorn, Sophia M V; Lewis, Terrence D; Healy, Mae W; Terry, Nancy; DeCherney, Alan H; Hill, Micah J

    2017-04-01

    To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI). An updated systematic review and meta-analysis. Not applicable. Patients undergoing OI-IUI for infertility. Exogenous P luteal support after OI-IUI. Live birth. Eleven trials were identified that met inclusion criteria and constituted 2,842 patients undergoing 4,065 cycles, more than doubling the sample size from the previous meta-analysis. In patients receiving gonadotropins for OI, clinical pregnancy (relative risk [RR] 1.56, 95% confidence interval [CI] 1.21-2.02) and live birth (RR 1.77, 95% CI 1.30-2.42) were more likely in P supplemented patients. These findings persisted in analysis of live birth per IUI cycle (RR 1.59, 95% CI 1.24-2.04). There were no data on live birth in clomiphene citrate or clomiphene plus gonadotropin cycles. There was no benefit on clinical pregnancy with P support for patients who underwent OI with clomiphene (RR 0.85, 95% CI 0.52-1.41) or clomiphene plus gonadotropins (RR 1.26, 95% CI 0.90-1.76). Progesterone luteal phase support is beneficial to patients undergoing ovulation induction with gonadotropins in IUI cycles. The number needed to treat is 11 patients to have one additional live birth. Progesterone support did not benefit patients undergoing ovulation induction with clomiphene citrate or clomiphene plus gonadotropins. Published by Elsevier Inc.

  1. Sweet taste threshold for sucrose inversely correlates with depression symptoms in female college students in the luteal phase.

    PubMed

    Nagai, Masanori; Matsumoto, Sayaka; Endo, Junko; Sakamoto, Reiko; Wada, Maki

    2015-03-15

    Influences of depression symptoms on the sweet taste threshold were investigated in healthy college students (30 males and 40 females). Depression symptoms were scored by SDS (Self-Rating Depression Scale), and anxiety levels by STAI (State- and Trait-Anxiety Inventory). Recognition thresholds for sucrose were determined. In female students, the menstrual phase on the day of the experiment was self-reported. Depression symptoms, anxiety levels, and the recognition threshold for sucrose were not different among the 3 groups, i.e. males, females in the follicular phase, and females in the luteal phase. Depression symptoms were positively correlated with state and trait anxiety in all groups. The sweet taste threshold was inversely correlated with depression symptoms (r=-0.472, p=0.031) and trait anxiety (r=-0.506, p=0.019) in females in the luteal phase. In males as well as females in the follicular phase, however, no correlation between sweet taste threshold and depression was found. The results show that the recognition threshold for sucrose reduces with increased depression in females with a higher anxiety trait, but only in the luteal phase. It is hypothesized that brain regions, which spatially overlap and are responsible for both aversive emotions and gustatory processing, are susceptible to periodic changes in gonadal hormones due to the menstrual cycle. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Analysis of human mammary fibroadenoma by Ki-67 index in the follicular and luteal phases of menstrual cycle.

    PubMed

    Rego, M F; Navarrete, M A L H; Facina, G; Falzoni, R; Silva, R; Baracat, E C; Nazario, A C P

    2009-04-01

    Fibroadenoma is the most common benign mammary condition among women aged 35 or younger. Expression of Ki-67 antigen has been used to compare proliferative activity of mammary fibroadenoma epithelium in the follicular and luteal phases of the menstrual cycle. Ninety eumenorrheic women were selected for tumour excision; they were assigned to either of the two groups, according to their phase of menstrual cycle. At the end of the study, 75 patients with 87 masses were evaluated by epithelial cell Ki-67 expression, blind (no information given concerning group to which any lesion belonged). Both groups were found to be homogeneous relative to age, menarche, body mass index, previous gestation, parity, breastfeeding, number of fibroadenomas, family history of breast cancer and tabagism. Median tumour size was 2.0 cm and no relationship between proliferative activity and nodule diameter was observed. No typical pattern was observed in the expression of Ki-67 in distinct nodules of the same patient. Average values for expression of Ki-67 (per 1000 epithelial cells) in follicular and luteal phases were 27.88 and 37.88, respectively (P = 0.116). Our findings revealed that proliferative activities in the mammary fibroadenoma epithelium did not present a statistically significant difference in the follicular and luteal phases. The present study contributes to clarifying that fibroadenoma is a neoplasm and does not undergo any change in the proliferative activity during the menstrual cycle.

  3. The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-{alpha}-induced apoptosis

    SciTech Connect

    Wagley, Yadav; Yoo, Yung-Choon; Seo, Han Geuk; Rhee, Man Hee; Kim, Tae-Hyoung; Kang, Keon Wook; Nah, Seung-Yeol; Oh, Jae-Wook . E-mail: ohjw@mail.chosun.ac.kr

    2007-03-23

    Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-{alpha} in combination with IFN-{gamma} in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-{alpha}-resistant B16/F10.9 melanoma cells. A low dose of TNF-{alpha} or IL-6/sIL-6R had minimal affect on the cell growth. However, the highly active fusion protein of sIL-6R and IL-6 (IL6RIL6), covalently linked by a flexible peptide, sensitized TNF-{alpha}-resistant F10.9 melanoma cells to TNF-{alpha}-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-{alpha} resulted in both the activation of caspase-3 and the reduction of bcl-2 expression. Flow cytometry analysis showed that IL6RIL6-upregulated TNF-R55 and TNF-R75 expression, suggesting an increase in TNF-{alpha} responsiveness by IL6RIL6 resulting from the induction of TNF receptors. Moreover, exposure of F10.9 cells to neutralizing antibody to TNF-R55 significantly inhibited IL6RIL6/TNF-{alpha}-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-{alpha}-resistant melanoma cells to TNF-{alpha}-induced apoptosis, may provide a new target for immunotherapy.

  4. Fluocinolone inhibits VEGF expression via glucocorticoid receptor in human retinal pigment epithelial (ARPE-19) cells and TNF-alpha-induced angiogenesis in chick chorioallantoic membrane (CAM).

    PubMed

    Ayalasomayajula, Surya P; Ashton, Paul; Kompella, Uday B

    2009-04-01

    The purpose of this study was to determine whether fluocinolone inhibits vascular endothelial growth factor (VEGF) expression in a retinal pigment epithelial cell line (ARPE-19) and TNF-alpha-induced angiogenesis in chick chorioallantoic membrane (CAM) assay. The dose-dependent effect of fluocinolone (0.0001-1 microM) on VEGF secretion, VEGF mRNA expression, and cytotoxicity was determined in confluent monolayers of ARPE-19 cells using ELISA, RT-PCR, and MTT assay, respectively. The effect of a glucocorticoid receptor antagonist (RU486) on fluocinolone-mediated VEGF expression was determined. The effect of fluocinolone in inhibiting TNF-alpha-induced angiogenesis was determined using chick chorioallantoic membrane (CAM) assay. The dose-dependent effect of fluocinolone (0.0001-1 microM) in inhibiting 1% serum-stimulated ARPE-19 cell proliferation was determined using BrdU labeling assay. At concentrations devoid of cytotoxicity, fluocinolone inhibited VEGF secretion as well as mRNA expression in ARPE-19 cells. RU486 (1 microM) treatment prevented inhibition of VEGF secretion and VEGF mRNA expression by fluocinolone (0.1 microM). Fluocinolone (50 ng/egg) inhibited angiogenesis induced by TNF-alpha. The ARPE-19 cell proliferation was inhibited by fluocinolone in a dose-dependent manner. Fluocinolone inhibited VEGF expression in ARPE-19 cells via its glucocorticoid receptor activity. In addition, fluocinolone inhibited proliferation of ARPE-19 cells and TNF-alpha-induced angiogenesis in chorioallantoic membranes.

  5. Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population.

    PubMed

    Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

    2016-07-05

    Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10-3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10-7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP.

  6. Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

    PubMed Central

    Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

    2016-01-01

    Background: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Methods: Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. Results: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10−3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10−7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Conclusions: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID:27364786

  7. Change of uterine histroph proteins during follicular and luteal phase in pigs.

    PubMed

    Lee, Sang-Hee; Song, Eun-Ji; Hwangbo, Yong; Lee, Seunghyung; Park, Choon-Keun

    2016-05-01

    The aim of this study was to examine protein expression patterns of uterine histroph (UH) during the follicular phase (FP) and luteal phase (LP) in pigs. Forty-nine common proteins were identified from FP and LP samples; five were significantly down-regulated (>1.5-fold), while 15 were significantly up-regulated (>1.5-fold) in LPUH compared with FPUH (P<0.05). The 20 differentially-expressed proteins are involved in cell proliferation, cell responses, translation, transport, and metabolism and their molecular functions include nucleic acid binding, oxygen activity, enzymatic activity, growth activity, iron binding, and redox binding. Protein expression of vascular endothelial growth factor D (VEGFD), coatomer subunit gamma-2 (G2COP), collagen alpha 4 chain (COL4), cysteine rich protein 2 (CRP2), myoglobin (MYG), and galactoside 3-L-fucosyltransferase 4 (FUT4) was analyzed by Western blotting. These proteins were significantly higher in LPUH compared to FPUH (P<0.05). These data expand our understanding of changes in the intrauterine environment during the pre-implantation period in pigs. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effect of parity and fetal sex on placental and luteal hormones during early first trimester.

    PubMed

    Järvelä, Ilkka Y; Záčková, Tamara; Laitinen, Päivi; Ryynänen, Markku; Tekay, Aydin

    2012-02-01

    Earlier studies have shown that maternal hormone secretion during late first or second trimester may be affected by gravidity. We examined the luteoplacental hormone secretion during 5-11 weeks of gestation in relation to gravidity. Forty-one naturally conceived pregnancies underwent weekly assessment of serum human chorionic gonadotrophin, progesterone and 17-OH progesterone, estradiol, testosterone, and pregnancy-associated plasma protein A levels. In addition, the volume and the vasculature of the dominant ovary with corpus luteum were assessed with the use of a 3-dimensional power Doppler ultrasonography. Areas under the curve for hormonal and ultrasonographic parameters were calculated. Twenty-two out of the 41 women were pregnant for the first time. All the pregnancies were uncomplicated and resulted in term deliveries of appropriately grown newborns. During pregnancy weeks 5-11, the secretion (area under the curve) of human chorionic gonadotrophin (6.54 ± 0.03 vs 6.39 ± 0.05, p = 0.010), progesterone (3.49 ± 0.02 vs 3.36 ± 0.03, p = 0.003), and 17-OH progesterone (2.73 ± 0.03 vs 2.62 ± 0.03, p = 0.013) were higher in primigravid than in multigravid women. No other differences were detected between primigravid and multigravid women. The placental function already differs between primigravid and multigravid women during the first weeks of pregnancy, which reflects the corpus luteal function. © 2012 John Wiley & Sons, Ltd.

  9. Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies.

    PubMed

    Conrad, Kirk P; Baker, Valerie L

    2013-01-15

    Investigations in the rat model of pregnancy indicate an important role for the corpus luteal (CL) hormone relaxin in the maternal circulatory and osmoregulatory changes in pregnancy, which are epitomized by profound vasodilation and modest hypoosmolality, respectively. In a pilot study of infertile women who became pregnant through donor eggs, in vitro fertilization, and embryo transfer, the gestational rise in glomerular filtration and fall in plasma osmolality were markedly subdued. Because these women were infertile, they lacked a CL and circulating relaxin (and possibly other vasoactive CL hormones). Based on these findings in pregnant rats and women, we hypothesize that infertile women conceiving through donor eggs will have overall subdued circulatory changes (e.g., attenuated reduction in systemic vascular resistance and subdued increase in cardiac output) particularly during early pregnancy when CL hormones predominate before the full development and maturation of the placenta. In contrast, infertile women conceiving by autologous eggs retrieved after ovarian stimulation and fresh embryo transfer may have a relatively hyperdynamic circulation due to the presence of many CL (up to 20 or more) and higher circulating levels of vasodilatory ovarian hormones such as relaxin. Emerging evidence suggests that women undergoing Assisted Reproductive Technologies (ART) have increased risk for adverse pregnancy outcomes such as preeclampsia and small for gestational-age babies. This increased risk may be partly caused by the maternal milieu, which is not physiological in ART pregnancies due to the abnormal status of the CL.

  10. Relaxin in sera during the luteal phase of in-vitro fertilization cycles.

    PubMed

    Eddie, L W; Martinez, F; Healy, D L; Sutton, B; Bell, R J; Tregear, G W

    1990-03-01

    To identify the time when relaxin can first be detected in peripheral sera after in-vitro fertilization (IVF) and embryo transfer, blood samples were collected from 20 women up to 14 days after oocyte retrieval. Sixteen women did not become pregnant and in eight of them relaxin (but not beta-human chorionic gonadotrophin, beta-hCG) was measurable for the first time at days 6 to 12. Concentrations of other hormones measured were also different in these eight women compared with the remaining eight non-pregnant women; their serum concentrations of 17 alpha-OH progesterone, progesterone and oestradiol were higher but concentrations of luteinizing hormone and follicle-stimulating hormone were lower. Three women became pregnant; relaxin and beta-hCG were first detected on the same day (10 to 12). The remaining woman had increased beta-hCG levels but did not develop a clinical pregnancy. Measurement of serum relaxin during IVF cycles may allow assessment of corpora luteal function before its identification by levels of steroid hormones.

  11. Circadian variation of sleep during the follicular and luteal phases of the menstrual cycle.

    PubMed

    Shechter, Ari; Varin, France; Boivin, Diane B

    2010-05-01

    Women experience insomnia more frequently than men. Menstrual cycle changes in reproductive hormones and circadian rhythms may contribute to sleep disruptions. Our aim, therefore, was to clarify the interaction between menstrual and circadian processes as it affects sleep. Participants entered the laboratory during the mid-follicular (MF) and mid-luteal (ML) phases of their menstrual cycle for an ultra-rapid sleep-wake cycle (URSW) procedure, consisting of 36 cycles of 60-min wake episodes alternating with 60-min nap opportunities. This procedure concluded with an ad libitum nap episode. Time-isolation suite. Eight unmedicated, physically and mentally healthy females with regular ovulatory menstrual cycles. N/A. Polysomnographic sleep from nocturnal sleep episodes and 60-min naps; subjective alertness; core body temperature (CBT); salivary melatonin; urinary estradiol; and urinary progesterone. Increased CBT values at night and decreased CBT amplitude were observed during ML compared to MF. Circadian phase of CBT and the circadian melatonin profile were unaffected by menstrual phase. All analyzed sleep parameters showed a circadian variation throughout the URSW procedure, with no menstrual phase differences observed for most, including slow wave sleep (SWS). The circadian variation of REM sleep duration, however, was sensitive to menstrual phase, with reduced REM sleep during ML at circadian phase 0 degrees and 30 degrees. Moderate but significant changes in REM sleep across the menstrual and circadian cycles were observed. These results support an interaction between circadian and menstrual processes in the regulation of REM sleep.

  12. Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer improves cycle outcome.

    PubMed

    Haas, Jigal; Lantsberg, Daniel; Feldman, Noa; Manela, Daphna; Machtinger, Ronit; Dar, Shir; Rabinovici, Jaron; Orvieto, Raoul

    2015-01-01

    With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive β-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

  13. Comparison of intravaginal progesterone gel and intramuscular 17-α-hydroxyprogesterone caproate in luteal phase support.

    PubMed

    Satir, Funda; Toptas, Tayfun; Inel, Murat; Erman-Akar, Munire; Taskin, Omur

    2013-06-01

    The main objective of this study was to compare the pregnancy rates of intramuscular (IM) 17-α-hydroxyprogesterone caproate (17-HPC) and intravaginal (IV) progesterone gel administration in in vitro fertilization-embryo transfer (IVF-ET) cycles. The IM 17-HPC and IV progesterone groups included 632 (66.4%) and 320 (33.6%) women undergoing the first cycles of IVF-ET treatment, respectively. Multivariate analyses annotated for all potential confounders showed that the use of IV progesterone retained a predictive value for the total β-human chorionic gonadotropin (hCG) positivity and clinical pregnancy rates [adjusted odds ratio (OR), 1.97; 95% confidence interval (CI), 1.28-3.03; P=0.002; and OR, 1.66; 95% CI, 1.07-2.60; P=0.03, respectively]. However, biochemical and on-going pregnancy rates did not differ significantly between the groups (OR, 1.85; 95% CI, 1.00-3.41; P=0.05; and OR, 1.43, 95% CI, 0.89-2.30; P=0.14, respectively). Luteal phase support (LPS) with IV progesterone gel in comparison with IM 17-HPC appears to be associated with higher clinical pregnancy rates in IVF-ET cycles. However, this benefit is clinically irrelevant in terms of on-going pregnancy outcomes.

  14. Comparison of intravaginal progesterone gel and intramuscular 17-α-hydroxyprogesterone caproate in luteal phase support

    PubMed Central

    SATIR, FUNDA; TOPTAS, TAYFUN; INEL, MURAT; ERMAN-AKAR, MUNIRE; TASKIN, OMUR

    2013-01-01

    The main objective of this study was to compare the pregnancy rates of intramuscular (IM) 17-α-hydroxyprogesterone caproate (17-HPC) and intravaginal (IV) progesterone gel administration in in vitro fertilization-embryo transfer (IVF-ET) cycles. The IM 17-HPC and IV progesterone groups included 632 (66.4%) and 320 (33.6%) women undergoing the first cycles of IVF-ET treatment, respectively. Multivariate analyses annotated for all potential confounders showed that the use of IV progesterone retained a predictive value for the total β-human chorionic gonadotropin (hCG) positivity and clinical pregnancy rates [adjusted odds ratio (OR), 1.97; 95% confidence interval (CI), 1.28–3.03; P=0.002; and OR, 1.66; 95% CI, 1.07–2.60; P=0.03, respectively]. However, biochemical and on-going pregnancy rates did not differ significantly between the groups (OR, 1.85; 95% CI, 1.00–3.41; P=0.05; and OR, 1.43, 95% CI, 0.89–2.30; P=0.14, respectively). Luteal phase support (LPS) with IV progesterone gel in comparison with IM 17-HPC appears to be associated with higher clinical pregnancy rates in IVF-ET cycles. However, this benefit is clinically irrelevant in terms of on-going pregnancy outcomes. PMID:23837065

  15. Relaxin secretion by porcine large luteal cells: effect of protein synthesis inhibitors.

    PubMed

    Taylor, M J; Clark, C L

    1993-02-01

    The purpose of the experiments reported herein was to investigate the relative importance of new hormone synthesis to basal and prostaglandin E2-stimulated rates of relaxin release. A relaxin-reverse hemolytic plaque assay was used to monitor relaxin release from individual large luteal cells (LLC) in which new protein synthesis was inhibited by cycloheximide or actinomycin D. These treatments significantly decreased the rate of relaxin release. In addition, cycloheximide reduced the total fraction of LLC possessing the ability to form plaques by about 10%, suggesting complete suppression of relaxin from this subset of cells. Exposure of inhibitor-treated LLC to prostaglandin E2 (a relaxin stimulatory secretagogue) enhanced relaxin release, and restored suppressed LLC back into the secretory population. Taken overall, these results demonstrate that the majority of relaxin-releasing LLC exploit a mixture of newly synthesized and older, stored hormone to achieve basal secretion. A minority of relaxin-releasing LLC, however, appear to depend wholly on newly synthesized hormone for basal secretion. The differential activity (and interaction) of these pathways in individual LLC may provide a potential explanation for the markedly heterogenous manner of hormone release observed in this (and other) cell types, and for the action of relaxin secretagogues.

  16. NCCS Regression Test Harness

    SciTech Connect

    Tharrington, Arnold N.

    2015-09-09

    The NCCS Regression Test Harness is a software package that provides a framework to perform regression and acceptance testing on NCCS High Performance Computers. The package is written in Python and has only the dependency of a Subversion repository to store the regression tests.

  17. NCCS Regression Test Harness

    SciTech Connect

    Tharrington, Arnold N.

    2015-09-09

    The NCCS Regression Test Harness is a software package that provides a framework to perform regression and acceptance testing on NCCS High Performance Computers. The package is written in Python and has only the dependency of a Subversion repository to store the regression tests.

  18. Regressive systemic sclerosis.

    PubMed Central

    Black, C; Dieppe, P; Huskisson, T; Hart, F D

    1986-01-01

    Systemic sclerosis is a disease which usually progresses or reaches a plateau with persistence of symptoms and signs. Regression is extremely unusual. Four cases of established scleroderma are described in which regression is well documented. The significance of this observation and possible mechanisms of disease regression are discussed. Images PMID:3718012

  19. Unitary Response Regression Models

    ERIC Educational Resources Information Center

    Lipovetsky, S.

    2007-01-01

    The dependent variable in a regular linear regression is a numerical variable, and in a logistic regression it is a binary or categorical variable. In these models the dependent variable has varying values. However, there are problems yielding an identity output of a constant value which can also be modelled in a linear or logistic regression with…

  20. Unitary Response Regression Models

    ERIC Educational Resources Information Center

    Lipovetsky, S.

    2007-01-01

    The dependent variable in a regular linear regression is a numerical variable, and in a logistic regression it is a binary or categorical variable. In these models the dependent variable has varying values. However, there are problems yielding an identity output of a constant value which can also be modelled in a linear or logistic regression with…

  1. Exogenous estradiol enhances apoptosis in regressing post-partum rat corpora lutea possibly mediated by prolactin

    PubMed Central

    Goyeneche, Alicia A; Telleria, Carlos M

    2005-01-01

    Background In pregnant rats, structural luteal regression takes place after parturition and is associated with cell death by apoptosis. We have recently shown that the hormonal environment is responsible for the fate of the corpora lutea (CL). Changing the levels of circulating hormones in post-partum rats, either by injecting androgen, progesterone, or by allowing dams to suckle, was coupled with a delay in the onset of apoptosis in the CL. The objectives of the present investigation were: i) to examine the effect of exogenous estradiol on apoptosis of the rat CL during post-partum luteal regression; and ii) to evaluate the post-partum luteal expression of the estrogen receptor (ER) genes. Methods In a first experiment, rats after parturition were separated from their pups and injected daily with vehicle or estradiol benzoate for 4 days. On day 4 post-partum, animals were sacrificed, blood samples were taken to determine serum concentrations of hormones, and the ovaries were isolated to study apoptosis in situ. In a second experiment, non-lactating rats after parturition received vehicle, estradiol benzoate or estradiol benzoate plus bromoergocryptine for 4 days, and their CL were isolated and used to study apoptosis ex vivo. In a third experiment, we obtained CL from rats on day 15 of pregnancy and from non-lactating rats on day 4 post-partum, and studied the expression of the messenger RNAs (mRNAs) encoding the ERalpha and ERbeta genes. Results Exogenous administration of estradiol benzoate induced an increase in the number of apoptotic cells within the CL on day 4 post-partum when compared with animals receiving vehicle alone. Animals treated with the estrogen had higher serum prolactin and progesterone concentrations, with no changes in serum androstenedione. Administration of bromoergocryptine blocked the increase in serum prolactin and progesterone concentrations, and DNA fragmentation induced by the estrogen treatment. ERalpha and ERbeta mRNAs were

  2. A preliminary study on the induction of dioestrous ovulation in the mare--a possible method for inducing prolonged luteal phase.

    PubMed

    Hedberg, Ylva; Dalin, Anne-Marie; Santesson, Malin; Kindahl, Hans

    2006-07-26

    Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle > or = 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles > or = 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle > or = 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness.

  3. Fully Regressive Melanoma

    PubMed Central

    Ehrsam, Eric; Kallini, Joseph R.; Lebas, Damien; Modiano, Philippe; Cotten, Hervé

    2016-01-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID:27672418

  4. Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

    PubMed

    Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit; Laursen, Rita Jakubcionyte; Povlsen, Betina Boel; Thomsen, Lise; Humaidan, Peter

    2015-10-01

    Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone. A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014. Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups. The number of patients included is limited and conclusions need to be verified in a larger RCT. Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace

  5. Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

    PubMed Central

    Chandra, Neelima; Yousefieh, Nazita; Zalenskaya, Irina; Kimble, Thomas; Asin, Susana; Rollenhagen, Christiane; Anderson, Sharon M.; Herold, Betsy; Mesquita, Pedro M.M.; Richardson-Harman, Nicola; Cunningham, Tina; Schwartz, Jill L.; Doncel, Gustavo F.

    2016-01-01

    Abstract The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (CV) lavage (CVL), vaginal flora, and p24 antigen production from CV tissues after ex vivo human immunodeficiency virus (HIV) infection between follicular (FOL) and luteal (LUT) phases of the menstrual cycle. CV tissue biopsies, CV secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies). Participants (n = 39) were HIV-seronegative women not using exogenous hormone supplementation, with normal menstrual cycles, who were screened to exclude sexually transmitted and reproductive tract infections. Serum levels of estradiol and progesterone were significantly higher in the LUT versus the FOL phase of the menstrual cycle. Controlling for race, reported contraceptive use/sexual practices, and clinical trial, we found no differences in vaginal tissue immune cell populations and activation status, transcriptomes, inhibition of HIV, herpes simplex virus type 2 and Escherichia coli by the CVL, vaginal pH or Nugent score, or production of p24 antigen after ex vivo infection by HIV-1BaL between CV samples obtained in the FOL phase versus the LUT phase of the menstrual cycle. There were no significant correlations between serum estradiol and progesterone levels and CV endpoints. The hypothesis that the LUT phase of the menstrual cycle represents a more vulnerable stage for mucosal infection with HIV was not supported by data from samples obtained from the lower genital tract (ectocervix and vagina) from these two clinical trials. PMID:26750085

  6. Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows

    PubMed Central

    Hojo, Takuo; Siemieniuch, Marta J.; Lukasik, Karolina; Piotrowska-Tomala, Katarzyna K.; Jonczyk, Agnieszka W.; Okuda, Kiyoshi; Skarzynski, Dariusz J.

    2016-01-01

    Programmed necrosis (necroptosis) is an alternative form of programmed cell death that is regulated by receptor-interacting protein kinase (RIPK) 1 and 3-dependent, but is a caspase (CASP)-independent pathway. In the present study, to determine if necroptosis participates in bovine structural luteolysis, we investigated RIPK1 and RIPK3 expression throughout the estrous cycle, during prostaglandin F2α (PGF)-induced luteolysis in the bovine corpus luteum (CL), and in cultured luteal steroidogenic cells (LSCs) after treatment with selected luteolytic factors. In addition, effects of a RIPK1 inhibitor (necrostatin-1, Nec-1; 50 μM) on cell viability, progesterone secretion, apoptosis related factors and RIPKs expression, were evaluated. Expression of RIPK1 and RIPK3 increased in the CL tissue during both spontaneous and PGF-induced luteolysis (P < 0.05). In cultured LSCs, tumor necrosis factor α (TNF; 2.3 nM) in combination with interferon γ (IFNG; 2.5 nM) up-regulated RIPK1 mRNA and protein expression (P < 0.05). TNF + IFNG also up-regulated RIPK3 mRNA expression (P < 0.05), but not RIPK3 protein. Although Nec-1 prevented TNF + IFNG-induced cell death (P < 0.05), it did not affect CASP3 and CASP8 expression. Nec-1 decreased both RIPK1 and RIPK3 protein expression (P < 0.05). These findings suggest that RIPKs-dependent necroptosis is a potent mechanism responsible for bovine structural luteolysis induced by pro-inflammatory cytokines. PMID:27901113

  7. GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-A Systematic PRISMA Review and Meta-analysis.

    PubMed

    Haahr, Thor; Roque, Matheus; Esteves, Sandro C; Humaidan, Peter

    2017-01-01

    The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS

  8. Apoptosis-Related Factors in the Luteal Phase of the Domestic Cat and Their Involvement in the Persistence of Corpora Lutea in Lynx.

    PubMed

    Amelkina, Olga; Zschockelt, Lina; Painer, Johanna; Serra, Rodrigo; Villaespesa, Francisco; Braun, Beate C; Jewgenow, Katarina

    2015-01-01

    The corpus luteum (CL) is a transient gland formed in the ovary after ovulation and is the major source of progesterone. In the Iberian and Eurasian lynx, CL physiologically persist after parturition and retain their capacity to produce progesterone, thus suppressing the ovarian activity. This unique reproductive characteristic has a big impact on the success of assisted reproduction techniques in the endangered Iberian lynx. The mechanisms behind CL persistence are not yet understood and require extensive studies on potential luteotropic and luteolytic factors in felids. Because the apoptosis system has been shown to be involved in structural regression of CL in many species, we aimed to investigate the capacity of perCL to undergo apoptosis. In addition, we performed initial studies on the apoptosis system in the luteal phase of the domestic cat. No previous research on this system has been made in this species. Our factors of interest included agents of the intrinsic apoptosis pathway, i.e., pro-survival B-cell CLL/lymphoma 2 (BCL2) and pro-apoptotic BCL2-associated X protein (BAX), the executioner caspase-3 (CASP3), as well as of the extrinsic pathway, i.e., pro-apoptotic receptor FAS, and tumor necrosis factor (TNF) and its receptors (pro-apoptotic TNFRSF1A and pro-survival TNFRSF1B). We analyzed the relative mRNA levels of these factors, as well as protein localization of CASP3 and TNF during stages of pregnancy and the non-pregnant luteal phase in CL of domestic cats. The same factors were investigated in freshly ovulated CL (frCL) and perCL of Iberian and Eurasian lynx, which were histologically analyzed. All factors were present in the CL tissue of both domestic cat and lynx throughout all analyzed stages. The presence of pro-apoptotic factors BAX, CASP3, FAS and TNFRSF1A in perCL of the Eurasian and Iberian lynx might indicate the potential sensitivity of perCL to apoptotic signals. The expression of pro-survival factors BCL2 and TNFRSF1B was

  9. Apoptosis-Related Factors in the Luteal Phase of the Domestic Cat and Their Involvement in the Persistence of Corpora Lutea in Lynx

    PubMed Central

    Amelkina, Olga; Zschockelt, Lina; Painer, Johanna; Serra, Rodrigo; Villaespesa, Francisco; Braun, Beate C.; Jewgenow, Katarina

    2015-01-01

    The corpus luteum (CL) is a transient gland formed in the ovary after ovulation and is the major source of progesterone. In the Iberian and Eurasian lynx, CL physiologically persist after parturition and retain their capacity to produce progesterone, thus suppressing the ovarian activity. This unique reproductive characteristic has a big impact on the success of assisted reproduction techniques in the endangered Iberian lynx. The mechanisms behind CL persistence are not yet understood and require extensive studies on potential luteotropic and luteolytic factors in felids. Because the apoptosis system has been shown to be involved in structural regression of CL in many species, we aimed to investigate the capacity of perCL to undergo apoptosis. In addition, we performed initial studies on the apoptosis system in the luteal phase of the domestic cat. No previous research on this system has been made in this species. Our factors of interest included agents of the intrinsic apoptosis pathway, i.e., pro-survival B-cell CLL/lymphoma 2 (BCL2) and pro-apoptotic BCL2-associated X protein (BAX), the executioner caspase-3 (CASP3), as well as of the extrinsic pathway, i.e., pro-apoptotic receptor FAS, and tumor necrosis factor (TNF) and its receptors (pro-apoptotic TNFRSF1A and pro-survival TNFRSF1B). We analyzed the relative mRNA levels of these factors, as well as protein localization of CASP3 and TNF during stages of pregnancy and the non-pregnant luteal phase in CL of domestic cats. The same factors were investigated in freshly ovulated CL (frCL) and perCL of Iberian and Eurasian lynx, which were histologically analyzed. All factors were present in the CL tissue of both domestic cat and lynx throughout all analyzed stages. The presence of pro-apoptotic factors BAX, CASP3, FAS and TNFRSF1A in perCL of the Eurasian and Iberian lynx might indicate the potential sensitivity of perCL to apoptotic signals. The expression of pro-survival factors BCL2 and TNFRSF1B was

  10. Effects of different five-day progesterone-based fixed-time AI protocols on follicular/luteal dynamics and fertility in dairy cows

    PubMed Central

    GARCIA-ISPIERTO, Irina; LÓPEZ-GATIUS, Fernando

    2014-01-01

    This study compares in two experiments the responses of lactating dairy cows to four different progesterone-based protocols for fixed-time artificial insemination (FTAI) in terms of their effects on follicular/luteal dynamics and fertility. The protocols consisted of a progesterone intravaginal device fitted for five days, along with the administration of different combinations of gonadotropin releasing hormone, equine chorionic gonadotropin and a single or double dose (24 h apart) of prostaglandin F2α. In Experiment I, the data were derived from 232 lactating cows. Binary logistic regression identified no effects of treatment on ovulation failure or multiple ovulation 10 days post artificial insemination (AI). Based on the odds ratio, the likelihood of ovulation failure was lower (by a factor of 0.1) in cows showing at least one corpus luteum (CL) upon treatment than in cows lacking a CL; repeat breeders (> 3 AI) and cows with multiple CLs at treatment showed lower (by a factor of 0.44) and higher (by a factor of 9.0) risks of multiple ovulation, respectively, than the remaining animals. In Experiment II, the data were derived from 5173 AIs. The independent variable treatment failed to affect the conception rate 28–34 days post AI, twin pregnancy or early fetal loss 58–64 days post AI. The results of this study demonstrate the efficacy of 5-day progesterone-based protocols for FTAI. All four protocols examined were able to induce ovulation in both cyclic and non-cyclic animals so that FTAI returned a similar pregnancy rate to spontaneous estrus. Our results suggest that the ovarian response and fertility resulting from each treatment are due more to the effect of ovarian structures at treatment than to the different combinations of hormones investigated. PMID:25196275

  11. Adverse influence of coumestrol on secretory function of bovine luteal cells in the first trimester of pregnancy.

    PubMed

    Młynarczuk, J; Wróbel, M H; Kotwica, J

    2013-07-01

    Coumestrol is one of a few biologically active substances present in leguminous plants, which are widely used as fodder for ruminants. Depending on the doses, coumestrol acts on the reproductive processes as an estrogen-like factor or antiestrogen to evoke a decrease in ovulation frequency, elongation of estrous cycle duration. The aim of the current investigations was to study the influence of coumestrol on secretory function of luteal cells obtained from first trimester of pregnant cows. Luteal cells (2.5 × 10(5) /mL) from 3rd to 5th, 6th to 8th, and 9th to 12th week of pregnancy were preincubated for 24 h and incubated with coumestrol (1 × 10(-6) M) for successive 48 h and the medium concentrations of progesterone (P4), oxytocin (OT), prostaglandin (PG) E2 and F2α were determined. Moreover, the expression of mRNA for neurophysin-I/oxytocin (NP-I/OT; precursor of OT) and peptidyl-glycine-α-amidating mono-oxygenase (PGA, an enzyme responsible for post-translational OT synthesis) was determined after 8 h of treatment. Coumestrol did not affect P4 secretion but increased the secretion of OT from the cells collected at all stages of gestation studied. Hence, the ratio of P4 to OT was markedly decreased. Simultaneously, coumestrol increased the expression of NP-I/OT mRNA during 9th to 12th weeks of pregnancy, and mRNA for PGA during 3rd to 5th and 9th to 12th weeks of gestation. Furthermore, coumestrol decreased PGE2 secretion from luteal cells in all studied stages of pregnancy, while it affected PGF2α metabolite (PGFM) concentration only from week 3 to 5 of pregnancy. Obtained results suggest that coumestrol impairs secretory function of the corpus luteum (CL) and this way it can affect the maintenance of pregnancy in the cow.

  12. Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

    PubMed

    Zhang, Xiao-Mei; Lv, Fang; Wang, Pin; Huang, Xia-Man; Liu, Kai-Feng; Pan, Yu; Dong, Nai-Jun; Ji, Yu-Rong; She, Hong; Hu, Rong

    2015-02-01

    Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments.

  13. Progestin priming before gonadotrophin stimulation and AI improves embryo development and normalises luteal function in the cat.

    PubMed

    Stewart, Rosemary A; Crosier, Adrienne E; Pelican, Katharine M; Pukazhenthi, Budhan S; Sitzmann, Brandon D; Porter, Tom E; Wildt, David E; Ottinger, Mary Ann; Howard, JoGayle

    2015-01-01

    Exogenous gonadotrophins administered before AI can adversely alter endocrine dynamics and inhibit embryo development in felids. In the present study, we tested the hypothesis that priming the domestic cat ovary with progestin mitigates the negative influence of gonadotrophin therapy by normalising early embryogenesis and luteal function. Queens were given either: (1) progestin pretreatment plus chorionic gonadotrophins (n=8; primed); or (2) gonadotrophins only (n=8; unprimed). Ovulatory response was assessed laparoscopically, and cats with fresh corpora lutea (CL) were inseminated in utero. Ovariohysterectomy was performed 3 days later to recover intra-oviductal embryos for in vitro culture; one ovary was prepared for histology, and CL from the remaining ovary were excised and assessed for progesterone content and targeted gene expression. Of the six primed and seven unprimed queens inseminated, embryo(s) were recovered from five individuals per group. Embryos from progestin-primed donors more closely simulated normal stage in vivo development (P<0.05). No 2- or 4-cell embryos from either group developed beyond 16-cells in vitro; however, 50% of unprimed and 66.7% of primed (P>0.05) 5-16-cell embryos progressed to morulae or blastocysts by Day 4 of culture. Although histological characteristics were unaffected by progestin priming (P>0.05), luteal progesterone was unusually high (P<0.05) in unprimed compared with primed cats (72.4±5.8 vs. 52.2±5.5 ng mg(-1), respectively). Two genes associated with progesterone biosynthesis (luteinising hormone receptor and 3β-hydroxysteroid dehydrogenase) were upregulated in unprimed versus primed individuals (P=0.05 and P<0.05, respectively), indicating potential mechanistic pathways for the protective influence of pre-emptive progestin treatment. Building on earlier findings that progestin priming prevents spontaneous ovulation, increases ovarian sensitivity to gonadotrophins and ensures a normative endocrine environment

  14. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system.

    PubMed

    Bonaccorso, Stefania; Marino, Valentina; Puzella, Antonella; Pasquini, Massimo; Biondi, Massimo; Artini, Marco; Almerighi, Cristiana; Verkerk, Robert; Meltzer, Herbert; Maes, Michael

    2002-02-01

    There is now evidence that repeated administration of interferon-alpha (IFN-alpha) to patients with chronic active hepatitis and cancers induces depressive symptoms. There is also evidence that induction of the cytokine network modulates the serotonergic system and that major depression is related to activation of the cytokine network and disturbances in the serotonergic metabolism. The aims of this study were to examine the effects of IFN-alpha-based immunotherapy on the development of depressive symptoms in relation to its effects on plasma tryptophan and kynurenine and serum serotonin (5-HT). Eighteen patients affected by chronic active hepatitis C were treated with IFN-alpha (3-6 million units subcutaneously three to six times a week for 6 months) and had measurements of the previous parameters before starting immunotherapy and 2, 4, 16, and 24 weeks later. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A) scale, respectively. Immunochemotherapy with IFN-alpha (1) significantly increased the MADRS and HAM-A scores and serum kynurenine concentrations and (2) significantly reduced plasma tryptophan and serum 5-HT concentrations. IFN-alpha-based immunotherapy significantly increased the kynurenine per tryptophan quotient, which estimates the activity of indoleamine 2,3-dioxygenase, the major tryptophan-catabolizing enzyme, which is induced by IFNs. There are significant relationships between the IFN-alpha-induced changes in the MADRS score and serum kynurenine (positive) and 5-HT (negative) concentrations. Immunotherapy with IFN-alpha significantly increases the severity of depressive symptoms. The latter is related to changes in the serotonergic system, such as depletion of serum 5-HT and induction of the catabolism of tryptophan to kynurenine. It is suggested that the IFN-alpha-induced changes in the serotonergic turnover could play a role in the

  15. Effects of periovulatory gonadotrophin treatment on luteal function and endometrial expression of selected genes in cyclic pony mares.

    PubMed

    Köhne, Martin; Ille, Natascha; Erber, Regina; Adib Razavi, Mahsa S; Walter, Ingrid; Aurich, Christine

    2016-12-01

    Progestin concentration in plasma during the early luteal phase is crucial for endometrial function and conceptus development. We hypothesized that periovulatory gonadotrophin treatment via support of luteal function affects endometrial gene expression in horses. Effect of age was analyzed as well. Shetland mares (n = 8, age 4-25 years) were assigned to the following treatments during five consecutive cycles in alternating order following a cross-over design: treatment hCG/-: preovulatory injection of hCG, but no gonadotrophin injection at detection of ovulation, treatment -/hCG: no preovulatory gonadodrophin injection, but injection of hCG at detection of ovulation, treatment eCG/-: preovulatory injection of eCG, but no gonadotrophin injection at detection of ovulation, treatment -/eCG: no preovulatory gonadotrophin injection, but injection of eCG at detection of ovulation, treatment control: no treatment. Concentration of progestin was analyzed by ELISA from the day of ovulation until Day 10. On Day 10, endometrial cells were collected transvaginally by cytobrush technique. Expression of mRNA of cyclooxygenase-2 (COX-2), prostaglandin F2α-synthase, prostaglandin E-synthase, progesterone receptor (PR), estradiol receptor (E2R), acyl-CoA-dehydrogenase (ACAD), uteroglobin (UGB), uteroferrin, and uterocalin was analyzed by RT qPCR. Immunohistological staining of endometrial tissue, obtained via biopsy, was performed for COX-2, PR and UGB. The P4 concentration was influenced by day of cycle (P < 0.01), but not by treatment. No effects of age on gene expression were determined. Neither of the periovulatory gonadotrophin treatments nor age influenced mRNA expression of the genes of interest. Treatment did also not affect immunohistological staining of the endometrium. In contrast, age affected the percentage of PR positive stromal cells (e.g. mare 1 (4 years): 65.5 ± 2.6, mare 2 (24 years): 82.7 ± 2.2%, P < 0.05) and COX-2 positive stained ciliated cells

  16. Improved Regression Calibration

    ERIC Educational Resources Information Center

    Skrondal, Anders; Kuha, Jouni

    2012-01-01

    The likelihood for generalized linear models with covariate measurement error cannot in general be expressed in closed form, which makes maximum likelihood estimation taxing. A popular alternative is regression calibration which is computationally efficient at the cost of inconsistent estimation. We propose an improved regression calibration…

  17. Morse-Smale Regression

    PubMed Central

    Gerber, Samuel; Rübel, Oliver; Bremer, Peer-Timo; Pascucci, Valerio; Whitaker, Ross T.

    2012-01-01

    This paper introduces a novel partition-based regression approach that incorporates topological information. Partition-based regression typically introduce a quality-of-fit-driven decomposition of the domain. The emphasis in this work is on a topologically meaningful segmentation. Thus, the proposed regression approach is based on a segmentation induced by a discrete approximation of the Morse-Smale complex. This yields a segmentation with partitions corresponding to regions of the function with a single minimum and maximum that are often well approximated by a linear model. This approach yields regression models that are amenable to interpretation and have good predictive capacity. Typically, regression estimates are quantified by their geometrical accuracy. For the proposed regression, an important aspect is the quality of the segmentation itself. Thus, this paper introduces a new criterion that measures the topological accuracy of the estimate. The topological accuracy provides a complementary measure to the classical geometrical error measures and is very sensitive to over-fitting. The Morse-Smale regression is compared to state-of-the-art approaches in terms of geometry and topology and yields comparable or improved fits in many cases. Finally, a detailed study on climate-simulation data demonstrates the application of the Morse-Smale regression. Supplementary materials are available online and contain an implementation of the proposed approach in the R package msr, an analysis and simulations on the stability of the Morse-Smale complex approximation and additional tables for the climate-simulation study. PMID:23687424

  18. Morse–Smale Regression

    SciTech Connect

    Gerber, Samuel; Rubel, Oliver; Bremer, Peer -Timo; Pascucci, Valerio; Whitaker, Ross T.

    2012-01-19

    This paper introduces a novel partition-based regression approach that incorporates topological information. Partition-based regression typically introduces a quality-of-fit-driven decomposition of the domain. The emphasis in this work is on a topologically meaningful segmentation. Thus, the proposed regression approach is based on a segmentation induced by a discrete approximation of the Morse–Smale complex. This yields a segmentation with partitions corresponding to regions of the function with a single minimum and maximum that are often well approximated by a linear model. This approach yields regression models that are amenable to interpretation and have good predictive capacity. Typically, regression estimates are quantified by their geometrical accuracy. For the proposed regression, an important aspect is the quality of the segmentation itself. Thus, this article introduces a new criterion that measures the topological accuracy of the estimate. The topological accuracy provides a complementary measure to the classical geometrical error measures and is very sensitive to overfitting. The Morse–Smale regression is compared to state-of-the-art approaches in terms of geometry and topology and yields comparable or improved fits in many cases. Finally, a detailed study on climate-simulation data demonstrates the application of the Morse–Smale regression. Supplementary Materials are available online and contain an implementation of the proposed approach in the R package msr, an analysis and simulations on the stability of the Morse–Smale complex approximation, and additional tables for the climate-simulation study.

  19. Identity, Regression and Development.

    ERIC Educational Resources Information Center

    Kroger, Jane

    1996-01-01

    Seeks to review varied meanings regression has held within psychoanalytic and developmental literatures; focus on the forms, frequencies, and functions of regression when examining data from two structural developmental models addressing dimensions of normative adolescent identity development; and consider precipitants for different forms of…

  20. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    PubMed

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P < 0.05) FGF-2 in luteal tissue of Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P < 0.05) FGF-2 in luteal tissue of Brahman cows when compared w Day-13 or Day-19 Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P < 0.05) by PGE1 or PGE2 in Brahman cows when compared with Day-19 Brahman controls. ANG-2 was increased (P < 0.05) on Day 19 in Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P < 0.05) by PGE1 but not by PGE2 in Angus

  1. Boosted Beta Regression

    PubMed Central

    Schmid, Matthias; Wickler, Florian; Maloney, Kelly O.; Mitchell, Richard; Fenske, Nora; Mayr, Andreas

    2013-01-01

    Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1). Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures. PMID:23626706

  2. Effect of feeding level on luteal function and progesterone concentration in the vena cava during early pregnancy in gilts.

    PubMed

    Athorn, R Z; Stott, P; Bouwman, E G; Chen, T Y; Kennaway, D J; Langendijk, P

    2013-01-01

    This study assessed the effect of feeding level on progesterone concentration in the caudal vena cava during early pregnancy in gilts. Twenty-four Landrace gilts were allocated to either a high (2.8±0.02) or a low (1.5±0.01 kg day⁻¹) feeding level at Day 0 of pregnancy. Serial blood samples were collected every 15 min for 3 h before and 3 h after feeding on Days 6 and 9 of pregnancy. Embryo survival and development as well as in vitro luteal progesterone production were assessed at Day 10 of pregnancy. Progesterone concentration in the vena cava was pulsatile with gilts on the high feeding level having more pulses compared with Low gilts on Day 9 of pregnancy (P<0.05). On Day 6 the number of pulses did not differ significantly between treatments; however, the average progesterone concentration in the vena cava tended to be higher in the gilts on the high feeding level (P<0.10). Embryo survival at Day 10 was 92±3% for High gilts compared with 77±3% for Low gilts (P<0.05). No difference in embryo development between the treatments was seen. There was no difference between treatments in in vitro secretion of progesterone by luteal tissue. In conclusion, a high plane of nutrition positively affects progesterone secretion by the ovaries in early pregnancy.

  3. Prostaglandin F2 alpha administered in vivo induces Ca2+-dependent protein phosphorylation in rat luteal tissue

    SciTech Connect

    Baum, M.S.

    1989-01-01

    The present study was performed in order to further elucidate the mechanism of action of PGF2 alpha in luteolysis in the rat ovary. Seven days after priming with superovulatory doses of pregnant mare serum gonadotropin and human chorionic gonadotropin to induce luteal tissue formation, the rats were injected with a luteolytic dose of the prostaglandin F2 alpha analogue cloprostenol. The ovaries were then homogenized, a 30,000 x g supernatant and pellet were prepared, whereafter aliquots of the preparations were incubated in the presence of (gamma-/sup 32/P)ATP with or without Ca2+. The phosphorylated proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and localized by autoradiography. The presence of Ca2+ caused an increased phosphorylation of a 45 kDa protein band in the particulate, but not in the cytosol, fraction. Furthermore, PGF2 alpha rapidly increased the /sup 32/P incorporation into the same protein band of 45 kDa. Thus, the PGF2 alpha-stimulated /sup 32/P incorporation was Ca2+-dependent and seen only in the particulate fraction. These results suggest that PGF2 alpha in its role as a luteolytic agent stimulates a Ca2+-dependent phosphorylation of a specific protein in luteal membranes of the rat ovary.

  4. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement.

    PubMed

    Yovich, John L; Conceicao, Jason L; Stanger, James D; Hinchliffe, Peter M; Keane, Kevin N

    2015-08-01

    This study explores the relevance of mid-luteal serum hormonal concentrations in cryopreserved embryo transfer cycles conducted under hormone replacement therapy (HRT) control and which involved single-embryo transfer (SET) of 529 vitrified blastocysts. Widely ranging mid-luteal oestradiol and progesterone concentrations ensued from the unique HRT regimen. Oestradiol had no influence on clinical pregnancy or live birth rates, but an optimal progesterone range between 70 and 99 nmol/l (P < 0.005) was identified in this study. Concentrations of progesterone below 50 nmol/l and above 99 nmol/l were associated with decreased implantation rates. There was no clear interaction between oestradiol and progesterone concentrations but embryo quality grading did show a significant influence on outcomes (P < 0.001 and P = 0.002 for clinical pregnancy and live birth rates, respectively). Multiple comparison analysis showed that the progesterone effect was influential regardless of embryo grading, body mass index or the woman's age, either at vitrification or at cryopreserved embryo transfer. The results support the argument that careful monitoring of serum progesterone concentrations in HRT-cryopreserved embryo transfer is warranted and that further studies should explore pessary adjustments to optimize concentrations for individual women to enhance implantation rates.

  5. Temperature dependence of alpha-induced scintillation in the 1,1,4,4-tetraphenyl-1,3-butadiene wavelength shifter

    NASA Astrophysics Data System (ADS)

    Veloce, L. M.; Kuźniak, M.; Di Stefano, P. C. F.; Noble, A. J.; Boulay, M. G.; Nadeau, P.; Pollmann, T.; Clark, M.; Piquemal, M.; Schreiner, K.

    2016-06-01

    Liquid noble based particle detectors often use the organic wavelength shifter 1,1,4,4-tetraphenyl-1,3-butadiene (TPB) which shifts UV scintillation light to the visible regime, facilitating its detection, but which also can scintillate on its own. Dark matter searches based on this type of detector commonly rely on pulse-shape discrimination (PSD) for background mitigation. Alpha-induced scintillation therefore represents a possible background source in dark matter searches. The timing characteristics of this scintillation determine whether this background can be mitigated through PSD. We have therefore characterized the pulse shape and light yield of alpha induced TPB scintillation at temperatures ranging from 300 K down to 4 K, with special attention given to liquid noble gas temperatures. We find that the pulse shapes and light yield depend strongly on temperature. In addition, the significant contribution of long time constants above ~50 K provides an avenue for discrimination between alpha decay events in TPB and nuclear-recoil events in noble liquid detectors.

  6. Inhibition of tumor necrosis factor-{alpha}-induced expression of adhesion molecules in human endothelial cells by the saponins derived from roots of Platycodon grandiflorum

    SciTech Connect

    Kim, Ji Young; Kim, Dong Hee; Kim, Hyung Gyun; Song, Gyu-Yong; Chung, Young Chul; Roh, Seong Hwan; Jeong, Hye Gwang . E-mail: hgjeong@chosun.ac.kr

    2006-01-15

    Adhesion molecules play an important role in the development of atherogenesis and are produced by endothelial cells after being stimulated with various inflammatory cytokines. This study examined the effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. CKS significantly inhibited the TNF{alpha}-induced increase in monocyte adhesion to endothelial cells as well as decreased the protein and mRNA expression levels of vascular adhesion molecule-1 and intercellular cell adhesion molecule-1 on endothelial cells. Furthermore, CKS significantly inhibited the TNF{alpha}-induced production of intracellular reactive oxygen species (ROS) and activation of NF-{kappa}B by preventing I{kappa}B degradation and inhibiting I{kappa}B kinase activity. Overall, CKS has anti-atherosclerotic and anti-inflammatory activity, which is least in part the result of it reducing the cytokine-induced endothelial adhesion to monocytes by inhibiting intracellular ROS production, NF-{kappa}B activation, and cell adhesion molecule expression in endothelial cells.

  7. Fijiolides A and B, inhibitors of TNF-alpha-induced NFkappaB activation, from a marine-derived sediment bacterium of the genus Nocardiopsis.

    PubMed

    Nam, Sang-Jip; Gaudêncio, Susana P; Kauffman, Christopher A; Jensen, Paul R; Kondratyuk, Tamara P; Marler, Laura E; Pezzuto, John M; Fenical, William

    2010-06-25

    Fijiolide A, a potent inhibitor of TNF-alpha-induced NFkappaB activation, along with fijiolide B, were isolated from a marine-derived bacterium of the genus Nocardiopsis. The planar structures of fijiolides A (1) and B (2) were elucidated by interpretation of 2D NMR spectroscopic data, while the absolute configurations of these compounds were defined by interpretation of circular dichroism and 2D NMR data combined with application of the advanced Mosher's method. Fijiolides A and B are related to several recently isolated chloroaromatic compounds, which appear to be the Bergman cyclization products of enediyne precursors. Fijiolide A reduced TNF-alpha-induced NFkappaB activation by 70.3%, with an IC(50) value of 0.57 micro-M. Fijiolide B demonstrated less inhibition, only 46.5%, without dose dependence. The same pattern was also observed with quinone reductase (QR) activity: fijiolide A was found to induce quinone reductase-1 (QR1) with an induction ratio of 3.5 at a concentration of 20 microg/mL (28.4 microM). The concentration required to double the activity was 1.8 microM. Fijiolide B did not affect QR1 activity, indicating the importance of the nitrogen substitution pattern for biological activity. On the basis of these data, fijiolide A is viewed as a promising lead for more advanced anticancer testing.

  8. Why are we regressing?

    PubMed

    Jupiter, Daniel C

    2012-01-01

    In this first of a series of statistical methodology commentaries for the clinician, we discuss the use of multivariate linear regression. Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  9. George: Gaussian Process regression

    NASA Astrophysics Data System (ADS)

    Foreman-Mackey, Daniel

    2015-11-01

    George is a fast and flexible library, implemented in C++ with Python bindings, for Gaussian Process regression useful for accounting for correlated noise in astronomical datasets, including those for transiting exoplanet discovery and characterization and stellar population modeling.

  10. Understanding poisson regression.

    PubMed

    Hayat, Matthew J; Higgins, Melinda

    2014-04-01

    Nurse investigators often collect study data in the form of counts. Traditional methods of data analysis have historically approached analysis of count data either as if the count data were continuous and normally distributed or with dichotomization of the counts into the categories of occurred or did not occur. These outdated methods for analyzing count data have been replaced with more appropriate statistical methods that make use of the Poisson probability distribution, which is useful for analyzing count data. The purpose of this article is to provide an overview of the Poisson distribution and its use in Poisson regression. Assumption violations for the standard Poisson regression model are addressed with alternative approaches, including addition of an overdispersion parameter or negative binomial regression. An illustrative example is presented with an application from the ENSPIRE study, and regression modeling of comorbidity data is included for illustrative purposes.

  11. Multiple Linear Regression

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-12-01

    This chapter deals with the multiple linear regression. That is we investigate the situation where the mean of a variable depends linearly on a set of covariables. The noise is supposed to be gaussian. We develop the least squared method to get the parameter estimators and estimates of their precisions. This leads to design confidence intervals, prediction intervals, global tests, individual tests and more generally tests of submodels defined by linear constraints. Methods for model's choice and variables selection, measures of the quality of the fit, residuals study, diagnostic methods are presented. Finally identification of departures from the model's assumptions and the way to deal with these problems are addressed. A real data set is used to illustrate the methodology with software R. Note that this chapter is intended to serve as a guide for other regression methods, like logistic regression or AFT models and Cox regression.

  12. Growth and regression in bovine corpora lutea: regulation by local survival and death pathways.

    PubMed

    Skarzynski, D J; Piotrowska-Tomala, K K; Lukasik, K; Galvão, A; Farberov, S; Zalman, Y; Meidan, R

    2013-09-01

    The bovine corpus luteum (CL) is a transient gland with a life span of only 18 days in the cyclic cow. Mechanisms controlling CL development and secretory function may involve factors produced both within and outside this gland. Although luteinizing hormone (LH) surge is the main trigger of ovulation and granulosa cells luteinization, many locally produced agents such as arachidonic acid (AA) metabolites, growth factors and cytokines were shown to complement gonadotropins action in the process of CL development. Bovine CL is a highly vascular gland, where the very rapid angiogenesis rate (until Day 5 of the cycle) results in the development of a capillary network, endowing this gland with one of the highest blood flow rate per unit mass in the body. Angiogenesis in the developing CL is later followed by either controlled regression of the microvascular tree in the non-fertile cycle or maintenance and stabilization of the blood vessels, as seen during pregnancy. Different luteal cell types (both steroidogenic and accessory luteal cells: immune cells, endothelial cells, pericytes and fibroblasts) are involved in the pro- and/or anti-angiogenic responses. The balance between pro- and anti-angiogenic responses to the main luteolysin - prostaglandin F2α (PGF2α) could be decisive in whether or not PGF2α induces CL regression. Fibroblast growth factor-2 (FGF2) may be one of the factors that modulate the angiogenic response to PGF2α. Manipulation of local production and action of FGF2 will provide new tools for reproductive management of dairy cattle. Luteolysis is characterized by a rapid decrease in progesterone production, followed by structural regression. Factors like endothelin-1, cytokines (tumour necrosis factorα, interferons) and nitric oxide were all shown to play critical roles in functional and structural regression of the CL by inhibiting steroidogenesis and inducting apoptosis.

  13. Effect of cortisol on neurophysin I/oxytocin and peptidyl glycine-alpha-amidating mono-oxygenase mRNA expression in bovine luteal and granulosa cells.

    PubMed

    Ziolkowska, A; Mlynarczuk, J; Kotwica, J

    2013-01-01

    Cortisol stimulates the synthesis and secretion of oxytocin (OT) from bovine granulosa and luteal cells, but the molecular mechanisms of cortisol action remain unknown. In this study, granulosa cells or luteal cells from days 1-5 and 11-15 of the oestrous cycle were incubated for 4 or 8 h with cortisol (1 x 10(-5), 1 x 10(-7) M). After testing cell viability and hormone secretion (OT, progesterone, estradiol), we studied the effect of cortisol on mRNA expression for precursor of OT (NP-I/OT) and peptidyl glycine-alpha-amidating mono-oxygenase (PGA). The influence of RU 486 (1 x 10(-5) M), a progesterone receptor blocker and inhibitor of the glucocorticosteroid receptor (GR), on the expression for both genes was tested. Cortisol increased the mRNA expression for NP-I/OT and PGA in granulosa cells and stimulated the expression for NP-I/OT mRNA in luteal cells obtained from days 1-5 and days 11-15 of the oestrous cycle. Expression for PGA mRNA was increased only in luteal cells from days 11-15 of the oestrous cycle. In addition, RU 486 blocked the cortisol-stimulated mRNA expression for NP-I/OT and PGA in both types of cells. These data suggest that cortisol affects OT synthesis and secretion in bovine ovarian cells, by acting on the expression of key genes, that may impair ovary

  14. Formation of corpora lutea and central luteal cavities and their relationship with plasma progesterone levels and other metabolic parameters in dairy cattle.

    PubMed

    Perez-Marin, C

    2009-06-01

    The corpus luteum (CL) may be looked upon as a compact or cavitary structure. A number of papers have addressed the relationship between CL type and parameters such as fertility or progesterone levels. The present study assessed the morphological and functional sequence observed in cows with different CL types, comparing pre-ovulatory follicle size, progesterone levels, luteal tissue formation and some blood biochemical parameters (calcium, albumin, inorganic phosphorus, glucose, magnesium, copper and zinc), oestrus cycle length and oestrus expression, as a function of CL type. Twenty-eight lactating dairy cows from two commercial dairy farms in southern Spain were studied. Oestrus detection was performed by monitoring daily oestrus behaviour, and artificial insemination (AI) was performed using the AM/PM rule. Ovaries and uterus were sonographically examined and blood samples were collected to measure progesterone and various biochemical parameters. There was a slight tendency towards the appearance of luteal cavities when pre-ovulatory follicles were larger (1.9 +/- 0.2 vs 1.7 +/- 03; p = 0.074). Fertility was not affected by cavity presence (cavity = 42.9% and compact = 57.1%; n.s.). Luteal tissue and function were not modified as a function of CL type. Cows with luteal cavities displayed significantly higher levels of albumin, suggesting a possible metabolic influence on the formation of these structures, although specific research is required to confirm this observation.

  15. [Understanding logistic regression].

    PubMed

    El Sanharawi, M; Naudet, F

    2013-10-01

    Logistic regression is one of the most common multivariate analysis models utilized in epidemiology. It allows the measurement of the association between the occurrence of an event (qualitative dependent variable) and factors susceptible to influence it (explicative variables). The choice of explicative variables that should be included in the logistic regression model is based on prior knowledge of the disease physiopathology and the statistical association between the variable and the event, as measured by the odds ratio. The main steps for the procedure, the conditions of application, and the essential tools for its interpretation are discussed concisely. We also discuss the importance of the choice of variables that must be included and retained in the regression model in order to avoid the omission of important confounding factors. Finally, by way of illustration, we provide an example from the literature, which should help the reader test his or her knowledge.

  16. Effects of orexins A and B on expression of orexin receptors and progesterone release in luteal and granulosa ovarian cells.

    PubMed

    Cataldi, Natalia I; Lux-Lantos, Victoria A R; Libertun, Carlos

    2012-10-10

    Orexin-A and orexin-B are neuropeptides controlling sleep-wakefulness, feeding and neuroendocrine functions via their G protein-coupled receptors, orexin-1R and orexin-2R. They are synthesized in the lateral hypothalamus and project throughout the brain. Orexins and orexin receptors have also been described outside the brain. Previously we demonstrated the presence of both receptors in the ovary, their increased expression during proestrous afternoon and the dependence on the gonadotropins. Here we studied the effects of orexins on the mRNA expression of both receptors, by quantitative real-time PCR, on luteal cells from superovulated rat ovaries and granulosa cells from diethylstilbestrol-treated rat ovaries. Effects on progesterone secretion were also measured. In luteal cells, 1 nM of either orexin-A or orexin-B decreased progesterone secretion. Orexin-A treatment increased expression of both orexin-1R and orexin-2R mRNA. The effect on orexin-1R mRNA expression was abolished by an orexin-1R selective receptor antagonist SB-334867 and the effect on orexin-2R mRNA expression was abolished by a selective orexin-2R antagonist JNJ-10397049. Orexin-B did not modify orexin-1R mRNA expression, but increased orexin-2R mRNA expression. The effect of orexin-B on orexin-2R was abolished by a selective orexin-2R antagonist. Neither the expression of orexin receptors nor progesterone secretions by granulosa cells were affected by orexins. FSH, as positive control, increased both steroid hormones secretion, but did not induce the expression of OX receptors in granulosa cells isolated from late preantral/early antral follicles. Finally in ovaries obtained immediately after sacrifice, the expression of orexin-1R and orexin-2R was higher in superovulated rat ovaries compared to control or diethylstilbestrol treated rat ovaries. A selective presence and function of both orexinergic receptors in luteal and granulosa cells is described, suggesting that the orexinergic system may

  17. Practical Session: Logistic Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    An exercise is proposed to illustrate the logistic regression. One investigates the different risk factors in the apparition of coronary heart disease. It has been proposed in Chapter 5 of the book of D.G. Kleinbaum and M. Klein, "Logistic Regression", Statistics for Biology and Health, Springer Science Business Media, LLC (2010) and also by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr341.pdf). This example is based on data given in the file evans.txt coming from http://www.sph.emory.edu/dkleinb/logreg3.htm#data.

  18. Metamorphic Geodesic Regression

    PubMed Central

    Hong, Yi; Joshi, Sarang; Sanchez, Mar; Styner, Martin; Niethammer, Marc

    2013-01-01

    We propose a metamorphic geodesic regression approach approximating spatial transformations for image time-series while simultaneously accounting for intensity changes. Such changes occur for example in magnetic resonance imaging (MRI) studies of the developing brain due to myelination. To simplify computations we propose an approximate metamorphic geodesic regression formulation that only requires pairwise computations of image metamorphoses. The approximated solution is an appropriately weighted average of initial momenta. To obtain initial momenta reliably, we develop a shooting method for image metamorphosis. PMID:23286131

  19. Luteolytic effect of LH: inhibition of 3 beta-hydroxysteroid dehydrogenase and stimulation of 20 alpha-hydroxysteroid dehydrogenase luteal activities in late pregnant rats.

    PubMed

    Stocco, C O; Deis, R P

    1996-09-01

    The mechanisms associated with the onset of luteolysis in the pregnant rat are not well known. The effect of a specific rat LH antiserum (AS-rLH) and of ovine LH (oLH) on luteal steroidogenesis on day 19 of pregnancy was examined. Rat LH antiserum administered intrabursally at 1000-1100 h on day 19 of pregnancy prevented the physiological decrease in 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity, the increase in 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity and the fall in serum progesterone (P4) level observed at 1800 h on day 21 of pregnancy. To see if oLH has a direct effect on luteal steroidogenesis, the gonadotrophin was injected into the periovarian bursa. The intrabursa treatment with 1 microgram oLH on day 19 of pregnancy at 0800-0900 h did not modify corpus luteal function 36 h after treatment, but treatment with 4 micrograms oLH per ovary induced a significant progressive decrease in luteal 3 beta-HSD activity starting 12 h after treatment, while a significant increase in 20 alpha-HSD activity, concomitant with a decrease in serum P4 level, occurred 48 h after treatment. Luteal P4 content decreased with respect to control groups 36 and 48 h after intrabursal treatment with 4 micrograms oLH. The intrabursal administration of 8 micrograms oLH induced an increase in 20 alpha-HSD activity and a decrease in 3 beta-HSD activity 36 h after treatment. Administration of 4 micrograms oLH per ovary on day 8 of pregnancy induced a significant increase in serum P4 levels without modifying 3 beta-HSD activity. In rats treated with oLH on day 19 of pregnancy the decrease in 3 beta-HSD activity occurred 36 h before the significant increase in 20 alpha-HSD activity and serum P4 level. In conclusion, the luteal enzymatic activity changes and the significant decrease in the intraluteal P4 concentration induced by the intrabursal administration of oLH and the clear effect of AS-rLH preventing the physiological luteal changes preceding parturition

  20. Effect of HIF-1a/VEGF signaling pathway on plasma progesterone and ovarian prostaglandin F₂a secretion during luteal development of pseudopregnant rats.

    PubMed

    Pan, X Y; Zhang, Z H; Wu, L X; Wang, Z C

    2015-08-03

    The corpus luteum is a temporary endocrine structure in mammals that plays an important role in the female reproductive cycle and is formed from a ruptured and ovulated follicle with rapid angiogenesis. Vascular endothelial growth factor (VEGF) is thought to be vital in normal and abnormal angiogenesis in the ovary, but the molecular regulation of luteal VEGF expression during corpus luteum development in vivo is still poorly understood at present. Therefore, we examined whether hypoxia-inducible factor-1a (HIF-1a) is induced and regulates VEGF expression and luteal function in vivo using a pseudopregnant rat model treated with a small-molecule inhibitor of HIF-1a, echinomycin. Corpus luteum development in the pseudopregnant rat ovary was determined after measuring plasma progesterone concentration and ovarian prostaglandin F2a content to reflect changes in HIF-1a and VEGF on different days of this developmental process. At day 7, the corpus luteum was formed and the expression of HIF- 1a/VEGF reached a maximum, while a significant decrease in HIF-1a/ VEGF expression was observed when luteolysis occurred at day 13. Additionally, echinomycin blocked luteal development by inhibiting VEGF expression mediated by HIF-1a and following luteal function by detecting the progesterone changes at day 7. These results demonstrated that HIF-1a-mediated VEGF expression might be an important mechanism regulating ovarian luteal development in mammals in vivo, which may provide new strategies for fertility control and for treating some types of ovarian dysfunction, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, and ovarian neoplasia.

  1. Effect of investigational kisspeptin/metastin analog, TAK-683, on luteinizing hormone secretion at different stages of the luteal phase in goats.

    PubMed

    Rahayu, Larasati Puji; El Behiry, Mohammed; Endo, Natsumi; Tanaka, Tomomi

    2017-03-25

    This study aimed to examine the response of luteinizing hormone (LH) secretion and ovarian steroid profile to TAK-683, an investigational metastin/kisspeptin analog, through treatment during different stages of the luteal phase in goats. Nine cycling Shiba goats (4.4 ± 2.3 years old) were assigned to early luteal phase (ELP, n = 4), mid-luteal phase (MLP, n = 4), and control (n = 5) groups. The ELP and MLP groups were administered 50 µg of TAK-683 intravenously on either day 5 or between days 7-14 after ovulation, respectively. The control group received vehicle between days 7-14 after ovulation. Blood samples were collected at 10-min (2-6 h), 2-h (6-24 h), and 24-h (24-96 h) intervals after treatment. Significant increases in plasma LH concentration were detected during the periods of 3 to 5 h and 2 to 5 h in the ELP and MLP groups, respectively. Estradiol concentrations continuously increased with the rise of basal LH secretion after TAK-683 treatment in two goats of the ELP group with a surge-like release of LH, but not in the goats without LH surge, i.e. the MLP and control group ones. Plasma progesterone concentration and the lengths of estrous cycle in all groups did not change significantly from the time before and after treatment. Present findings indicate that the responses of LH and ovarian steroids to treatment with TAK-683 depend on the stage of the luteal phase of the estrous cycle. We suggest that the stimulatory effects of TAK-683 on LH secretion are reduced in the process leading to the mid-luteal phase in cycling goats.

  2. Luteolytic action of RU486: modulation of luteal 3 beta-hydroxysteroid dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities in late pregnant rats.

    PubMed

    Tellería, C M; Stocco, C O; Deis, R P

    1995-06-01

    The effect of the synthetic antiprogestin RU486 on luteal function in late pregnant rats was studied by evaluating the activities of the enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). RU486 (2 mg/kg) administered to rats on day 18 of pregnancy at 10.00 h induced preterm delivery 26.4 +/- 0.35 h (n = 8) after treatment. Luteal 3 beta-HSD activity increased 24 and 34 h after RU486 injection, but a significant and progressive decrease started at 48 h with the maximal reduction 72 h after RU486 treatment, when compared with controls. Serum progesterone concentration decreased at the time of 3 beta-HSD activity reduction. Interestingly, 20 alpha-HSD activity started to increase 58 h after RU486 injection. The administration of the cyclooxygenase inhibitor, diclofenac (1.3 mg/kg), on days 17-19 of pregnancy to RU486-treated rats, delayed abortion and the duration of delivery, and prevented the decrease in 3 beta-HSD and the increase in 20 alpha-HSD activities observed 58 h after antiprogesterone treatment. RU486 administered intrabursally (1 microgram per ovary) on day 20 (14.00-15.00 h) increased 3 beta-HSD and decreased 20 alpha-HSD luteal activities at 18.00 h on day 21 of pregnancy, without modifying serum progesterone concentration, when compared with normal pregnant rats. In conclusion, the luteolytic process after preterm delivery induced by RU486 administration in late pregnant rats is characterized by a decrease in luteal 3 beta-HSD activity and circulating progesterone, which may trigger the increase in luteal 20 alpha-HSD activity. Prostaglandins seems to be involved in the increase of 20 alpha-HSD activity and therefore, in the demise of corpora lutea.

  3. Husbandry Factors and the Resumption of Luteal Activity in Open and Zero-Grazed Dairy Cows in Urban and Peri-Urban Kampala, Uganda

    PubMed Central

    Kanyima, BM; Båge, R; Owiny, DO; Ntallaris, T; Lindahl, J; Magnusson, U; Nassuna-Musoke, MG

    2014-01-01

    Contents The study investigated the influence of selected husbandry factors on interval to resumption of post-partum cyclicity among dairy cows in urban and peri-urban Kampala. A prospective study of 85 day post-partum period of 59 dairy cows in open (n = 38) and zero grazing (n = 21) systems was conducted on 24 farms. Cows of parity 1–6 were recruited starting 15–30 days post-partum. Progesterone (P4) content in milk taken at 10–12 day intervals was analysed using ELISA. The cow P4 profiles were classified into ‘normal’ (< 56 days), ‘delayed’ (> 56 days), ‘ceased’ or ‘prolonged’ (if started < 56 days but with abnormal P4 displays) resumption of luteal activity and tested for association with husbandry and cow factors. Of the 59 cows, luteal activity in 81.4% resumed normally and in 18.6%, delayed. Only 23.7% maintained regular luteal activity, while the others had ceased (10.2%), prolonged (37.3%) or unclear luteal activity (20.3%). There were no differences between open and zero-grazed cows. Milk production was higher (p < 0.05) in zero than open grazing, in urban than peri-urban and in cows fed on brew waste (p < 0.001) compared with mill products and banana peels. Results suggest that luteal activity resumes normally in a majority of cows, although only a minority experienced continued normal cyclicity once ovulation had occurred, in the two farming systems irrespective of feed supplements or water, and that supplementing with brew waste is beneficial for milk production. PMID:24930481

  4. Modern Regression Discontinuity Analysis

    ERIC Educational Resources Information Center

    Bloom, Howard S.

    2012-01-01

    This article provides a detailed discussion of the theory and practice of modern regression discontinuity (RD) analysis for estimating the effects of interventions or treatments. Part 1 briefly chronicles the history of RD analysis and summarizes its past applications. Part 2 explains how in theory an RD analysis can identify an average effect of…

  5. Explorations in Statistics: Regression

    ERIC Educational Resources Information Center

    Curran-Everett, Douglas

    2011-01-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This seventh installment of "Explorations in Statistics" explores regression, a technique that estimates the nature of the relationship between two things for which we may only surmise a mechanistic or predictive…

  6. Explorations in Statistics: Regression

    ERIC Educational Resources Information Center

    Curran-Everett, Douglas

    2011-01-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This seventh installment of "Explorations in Statistics" explores regression, a technique that estimates the nature of the relationship between two things for which we may only surmise a mechanistic or predictive…

  7. Multiple linear regression analysis

    NASA Technical Reports Server (NTRS)

    Edwards, T. R.

    1980-01-01

    Program rapidly selects best-suited set of coefficients. User supplies only vectors of independent and dependent data and specifies confidence level required. Program uses stepwise statistical procedure for relating minimal set of variables to set of observations; final regression contains only most statistically significant coefficients. Program is written in FORTRAN IV for batch execution and has been implemented on NOVA 1200.

  8. Multiple linear regression analysis

    NASA Technical Reports Server (NTRS)

    Edwards, T. R.

    1980-01-01

    Program rapidly selects best-suited set of coefficients. User supplies only vectors of independent and dependent data and specifies confidence level required. Program uses stepwise statistical procedure for relating minimal set of variables to set of observations; final regression contains only most statistically significant coefficients. Program is written in FORTRAN IV for batch execution and has been implemented on NOVA 1200.

  9. Modern Regression Discontinuity Analysis

    ERIC Educational Resources Information Center

    Bloom, Howard S.

    2012-01-01

    This article provides a detailed discussion of the theory and practice of modern regression discontinuity (RD) analysis for estimating the effects of interventions or treatments. Part 1 briefly chronicles the history of RD analysis and summarizes its past applications. Part 2 explains how in theory an RD analysis can identify an average effect of…

  10. Expression of tumor necrosis factor-alpha-induced protein 8 in pancreas tissues and its correlation with epithelial growth factor receptor levels.

    PubMed

    Liu, Ke; Qin, Cheng-Kun; Wang, Zhi-Yi; Liu, Su-Xia; Cui, Xian-Ping; Zhang, Dong-Yuan

    2012-01-01

    Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) is a recently identified protein considered to be associated with carcinogenesis. To investigate its expression pattern in pancreatic cancer patients and to analyse its correlation with clinicopathological significance and the expression levels of epithelial growth factor receptor (EGFR), immunohistochemistry was performed to detect the TNFAIP8 and EGFR proteins in pancreatic cancers, pancreatitis tissues, and healthy controls. The results showed stronger staining of TNFAIP8 protein in pancreatic cancer tissues compared with normal pancreas tissue. Furthermore, in 56 patients with pancreatic cancer, the expression levels of TNFAIP8 in patients with low tumor stage was higher than that with high tumor stage, and correlated with tumor staging and lymph node metastasis (P<0.05). Furthermore, TNFAIP8 expression positively correlated with EGFR levels (r=0.671135, P<0.05). These results indicate that TNFAIP8 may play important roles in the progression of pancreatic cancer.

  11. Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor alpha-induced signaling and apoptosis by downregulating tumor necrosis factor receptor 1.

    PubMed

    Morrison, Thomas E; Mauser, Amy; Klingelhutz, Aloysius; Kenney, Shannon C

    2004-01-01

    Tumor necrosis factor alpha (TNF-alpha) is a key mediator of host immune and inflammatory responses and inhibits herpesvirus replication by cytolytic and noncytolytic mechanisms. TNF-alpha effects are primarily mediated through the major TNF-alpha receptor, TNF-R1, which is constitutively expressed in most cell types. Here we show that the Epstein-Barr virus (EBV) immediate-early protein BZLF1 prevents TNF-alpha activation of target genes and TNF-alpha-induced cell death. These effects are mediated by down-regulation of the promoter for TNF-R1. Additionally, we demonstrate that expression of TNF-R1 is downregulated during the EBV lytic replication cycle. Thus, EBV has developed a novel mechanism for evading TNF-alpha antiviral effects during lytic reactivation or primary infection.

  12. eCG concentrations, luteal structures, return to cyclicity, and postabortion fertility in embryo transfer recipient mares.

    PubMed

    Cuervo-Arango, J; Aguilar, J J; Vettorazzi, M L; Martínez-Boví, R

    2015-10-01

    The present study characterizes the relationship between the levels of eCG, ovarian morphology, resumption of cyclicity, and fertility in postaborted embryo transfer recipient mares. A total of 32 pregnant recipient mares carrying a male fetus were aborted at approximately 65 days of gestation by single transcervical administration of cloprostenol. In addition, 25 gestation age-matched mares were used as nonaborted controls. The concentration of progesterone, but not of eCG, differed significantly between controls and aborted mares 48 hours after abortion. Of treated mares, 84.4% (27 of 32) expelled the fetus within 48 hours of treatment. The eCG concentration and the number of supplementary luteal structures were lower in mares aborted in November (equivalent to May in Northern Hemisphere) than in January. A total of 6.2%, 37.5%, and 56.2% of the mares entered anestrus, ovulated normally, and had 1 to 2 consecutive anovulatory cycles, respectively. The mean interval from abortion to the first ovulation was 28.5 ± 3.3 days (range, 5-65 days). The correlation between the levels of eCG at abortion and the interval to the first ovulation was poor (r = 0.38; P = 0.03). Of aborted mares, 90% (18 of 20) were reused and became pregnant after embryo transfer at a mean of 57.6 ± 4.4 days after abortion (range, 19-103 days) and eCG concentration of 0.9 ± 0.3 IU/mL (range, 0.1-3.6 IU/mL). In conclusion, the levels of eCG at the time of abortion were extremely variable and did not correlate well with the number of luteal structures or the interval from abortion to the first ovulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Sexual polymorphisms of vomeronasal 1 receptor family gene expression in bulls, steers, and estrous and early luteal-phase heifers

    PubMed Central

    KUBO, Haruna; OTSUKA, Midori; KADOKAWA, Hiroya

    2015-01-01

    Vomeronasal 1 receptors (V1R) are a family of receptors for intraspecies chemosignals, including pheromones, and are expressed in the olfactory epithelium (OE) and vomeronasal organ (VO). Even in the well-studied rodents, it is unclear which members of the V1R family cause sexual polymorphisms, as there are numerous genes and it is difficult to quantify their expressions individually. Bovine species carry only 34 V1R homologs, and the OE and VOs are large enough to sample. Here, V1R expression was quantified in the OE and VOs of individual bovines. Based on the 34 gene sequences, we obtained a molecular dendrogram consisting of four clusters and six independent branches. Semi-quantitative RT-PCR was used to obtain gene expression profiles in the VOs and OE of 5 Japanese Black bulls, 5 steers, 7 estrous heifers and 6 early luteal-phase heifers. Ten genes showed significant between-group differences, and 22 showed high expression in VOs than in OE. The bulls showed higher expression of one gene more in OE and another in VOs (both P<0.05) than did steers; both genes belonged to the first cluster. No genes were expressed more abundantly in steers than in bulls. The estrous heifers showed higher expression of a gene of the second cluster in OE, and a gene of the third cluster in VOs (both P<0.05) than did early luteal-phase heifers. These results suggest V1R expression exhibits sexual polymorphisms in cattle. PMID:26477467

  14. SOCS-1 and SOCS-3 inhibit IFN-alpha-induced expression of the antiviral proteins 2,5-OAS and MxA.

    PubMed

    Vlotides, George; Sörensen, Astrid S; Kopp, Florian; Zitzmann, Kathrin; Cengic, Neziha; Brand, Stephan; Zachoval, Reinhart; Auernhammer, Christoph J

    2004-07-30

    Although the use of IFN-alpha in combination with ribavirin has improved the treatment efficacy of chronic hepatitis C virus (HCV) infection, 20-50% of patients still fail to eradicate the virus depending on the HCV genotype. Recently, overexpression of HCV core protein has been shown to inhibit IFN signaling and induce SOCS-3 expression. Aim of this study was to examine the putative role of SOCS proteins in IFN resistance. By Western blot analysis, a 4-fold induction of STAT-1/3 phosphorylation by IFN-alpha was observed in mock-transfected HepG2 clones. In contrast, IFN-induced STAT-1/3 phosphorylation was considerably downregulated by SOCS-1/3 overexpression. In mock-transfected cells, IFN-alpha induced 2',5'-OAS and myxovirus resistance A (MxA) promoter activity 40- to 80-fold and 10- to 35-fold, respectively, and this effect was abrogated in SOCS-1/3 overexpressing cells. As detected by Northern blot technique, IFN-alpha potently induced 2',5'-OAS and MxA mRNA expression in the control clones. Overexpression of SOCS-1 completely abolished both 2',5'-OAS and MxA mRNA expression, whereas SOCS-3 mainly inhibited 2',5'-OAS mRNA expression. Our results demonstrate that SOCS-1 and SOCS-3 proteins inhibit IFN-alpha-induced activation of the Jak-STAT pathway and expression of the antiviral proteins 2',5'-OAS and MxA. These data suggest a potential role of SOCS proteins in IFN resistance during antiviral treatment.

  15. Ridge Regression: A Regression Procedure for Analyzing correlated Independent Variables

    ERIC Educational Resources Information Center

    Rakow, Ernest A.

    1978-01-01

    Ridge regression is a technique used to ameliorate the problem of highly correlated independent variables in multiple regression analysis. This paper explains the fundamentals of ridge regression and illustrates its use. (JKS)

  16. Ridge Regression Signal Processing

    NASA Technical Reports Server (NTRS)

    Kuhl, Mark R.

    1990-01-01

    The introduction of the Global Positioning System (GPS) into the National Airspace System (NAS) necessitates the development of Receiver Autonomous Integrity Monitoring (RAIM) techniques. In order to guarantee a certain level of integrity, a thorough understanding of modern estimation techniques applied to navigational problems is required. The extended Kalman filter (EKF) is derived and analyzed under poor geometry conditions. It was found that the performance of the EKF is difficult to predict, since the EKF is designed for a Gaussian environment. A novel approach is implemented which incorporates ridge regression to explain the behavior of an EKF in the presence of dynamics under poor geometry conditions. The basic principles of ridge regression theory are presented, followed by the derivation of a linearized recursive ridge estimator. Computer simulations are performed to confirm the underlying theory and to provide a comparative analysis of the EKF and the recursive ridge estimator.

  17. Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles.

    PubMed

    Chen, Hong; Wang, Yun; Lyu, Qifeng; Ai, Ai; Fu, Yonglun; Tian, Hui; Cai, Renfei; Hong, Qingqing; Chen, Qiuju; Shoham, Zeev; Kuang, Yanping

    2015-05-01

    To assess live-birth defects after a luteal-phase ovarian-stimulation regimen (LPS) for in vitro fertilization (IVF) and vitrified embryo transfer (ET) cycles. Retrospective cohort study. Tertiary-care academic medical center. Infants who were born between January 1, 2013 and May 1, 2014 from IVF with intracytoplasmic sperm injection (ICSI) treatments (n = 2,060) after either LPS (n = 587), the standard gonadotropin-releasing hormone-agonist (GnRH-a) short protocol (n = 1,257), or mild ovarian stimulation (n = 216). The three ovarian-stimulation protocols described and assisted reproductive technology (ART) treatment (IVF or ICSI, and vitrified ET) in ordinary practice. The main measures were: gestational age, birth weight and length, multiple delivery, early neonatal mortality, and birth defects. Associations were assessed using logistic regression by adjusting for confounding factors. The final sample included 2,060 live-born infants, corresponding to 1,622 frozen-thawed (FET) cycles, which led to: 587 live-born infants from LPS (458 FET cycles); 1,257 live-born infants from the short protocol (984 FET cycles); and 216 live-born infants from mild ovarian stimulation (180 FET cycles). Birth characteristics regarding gestational age, birth weight and length, multiple delivery, and early neonatal death were comparable in all groups. The incidence of live-birth defects among the LPS group (1.02%) and the short GnRH-a protocol group (0.64%) was slightly higher than in the mild ovarian-stimulation group (0.46%). However, none of these differences reached statistical significance. For congenital malformations, the risk significantly increased for the infertility-duration factor and multiple births; the adjusted odds ratios were 1.161 (95% confidence interval [CI]: 1.009-1.335) and 3.899 (95% CI: 1.179-12.896), respectively. No associations were found between congenital birth defects and various ovarian-stimulation regimens, maternal age, body mass index, parity

  18. Crinone Gel for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A Prospective Randomized Clinical Trial in the Chinese Population

    PubMed Central

    Zhao, Xiaoming; Ji, Xiaowei; Hong, Yan; Wang, Yuan; Zhu, Qinling; Xu, Bin; Sun, Yun

    2015-01-01

    To compare Crinone vaginal progesterone gel with intramuscularly injected progesterone for luteal phase support in progesterone-supplemented frozen-thawed embryo transfer (FET) cycles, a randomized prospective study of patients qualified for FET was conducted between September 2010 and January 2013 at a hospital in Shanghai, China. From the day of transformation into secretory phase endometrium (day 0), Crinone vaginal gel (90 mg/d) was administered to patients in the Gel Group, while progesterone (40 mg/d) was injected intramuscularly in patients in the Inj Group (n = 750 per group). All patients received oral dydrogesterone (20 mg/d) and estradiol valerate (4–8 mg/d). Day 3 embryos with the highest pre-frozen scores were transferred to patients in the two groups and the clinical outcomes compared. This study comprised 1,500 cycles (750 in each group). Twenty-nine cycles in the Gel Group and 24 in the Inj Group were withdrawn. There were no significant differences between groups in age, endometrial thickness, endometrial preparation time or number of embryos transferred. No significant differences were observed between the Gel Group and Inj Group in the rates of live birth (32.6% vs. 31.7%, P = 0.71), clinical pregnancy (40.1% vs. 40.6%, P = 0.831), implantation (25.8% vs. 25.3%, P = 0.772), abortion (16.3% vs. 18.3%, P = 0.514) or ectopic pregnancy (2.8% vs. 4.4%, P = 0.288). Multivariate logistic regression analysis revealed that the odds ratios (95% confidence intervals) for the rates of live birth, clinical pregnancy, abortion and ectopic pregnancy (Gel Group relative to Inj Group) were 1.036 (0.829–1.295), 0.971 (0.785–1.200), 0.919 (0.595–1.420) and 0.649 (0.261–1.614), respectively. Our study revealed that using Crinone vaginal gel in FET cycles achieved similar pregnancy outcomes to intramuscular progesterone, indicating that vaginal gel is a viable alternative to intramuscular injection. Trial Registration Chinese Clinical Trial Registry Chi

  19. In vivo intra-luteal implants of prostaglandin (PG) E1 or E2 (PGE1, PGE2) prevent luteolysis in cows. II: mRNA for PGF2α, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4 prostanoid receptors in luteal tissue.

    PubMed

    Weems, Yoshie S; Bridges, Phillip J; Jeoung, Myoungkun; Arreguin-Arevalo, J Alejandro; Nett, Torrance M; Vann, Rhonda C; Ford, Stephen P; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2012-01-01

    Previously, it was reported that chronic intra-uterine infusion of PGE(1) or PGE(2) every 4h inhibited luteolysis in ewes by altering luteal mRNA for luteinizing hormone (LH) receptors and unoccupied and occupied luteal LH receptors. However, estradiol-17β or PGE(2) given intra-uterine every 8h did not inhibit luteolysis in cows, but infusion of estradiol+PGE(2) inhibited luteolysis. In contrast, intra-luteal implants containing PGE(1) or PGE(2) in Angus or Brahman cows also inhibited the decline in circulating progesterone, mRNA for LH receptors, and loss of unoccupied and occupied receptors for LH to prevent luteolysis. The objective of this experiment was to determine how intra-luteal implants of PGE(1) or PGE(2) alter mRNA for prostanoid receptors and how this could influence luteolysis in Brahman or Angus cows. On day-13 Angus cows received no intra-luteal implant and corpora lutea were retrieved or Angus and Brahman cows received intra-luteal silastic implants containing Vehicle, PGE(1), or PGE(2) and corpora lutea were retrieved on day-19. Corpora lutea slices were analyzed for mRNA for prostanoid receptors (FP, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4) by RT-PCR. Day-13 Angus cow luteal tissue served as pre-luteolytic controls. mRNA for FP receptors decreased in day-19 Vehicle controls compared to day-13 Vehicle controls regardless of breed. PGE(1) and PGE(2) up-regulated FP gene expression on day-19 compared to day-19 Vehicle controls regardless of breed. EP1 mRNA was not altered by any treatment. PGE(1) and PGE(2) down-regulated EP2 and EP4 mRNA compared to day-19 Vehicle controls regardless of breed. PGE(1) or PGE(2) up-regulated mRNA EP3B receptor subtype compared to day-19 Vehicle control cows regardless of breed. The similarities in relative gene expression profiles induced by PGE(1) and PGE(2) support their agonistic effects. We conclude that both PGE(1) and PGE(2) may prevent luteolysis by altering expression of mRNA for prostanoid

  20. Steganalysis using logistic regression

    NASA Astrophysics Data System (ADS)

    Lubenko, Ivans; Ker, Andrew D.

    2011-02-01

    We advocate Logistic Regression (LR) as an alternative to the Support Vector Machine (SVM) classifiers commonly used in steganalysis. LR offers more information than traditional SVM methods - it estimates class probabilities as well as providing a simple classification - and can be adapted more easily and efficiently for multiclass problems. Like SVM, LR can be kernelised for nonlinear classification, and it shows comparable classification accuracy to SVM methods. This work is a case study, comparing accuracy and speed of SVM and LR classifiers in detection of LSB Matching and other related spatial-domain image steganography, through the state-of-art 686-dimensional SPAM feature set, in three image sets.

  1. Structural regression trees

    SciTech Connect

    Kramer, S.

    1996-12-31

    In many real-world domains the task of machine learning algorithms is to learn a theory for predicting numerical values. In particular several standard test domains used in Inductive Logic Programming (ILP) are concerned with predicting numerical values from examples and relational and mostly non-determinate background knowledge. However, so far no ILP algorithm except one can predict numbers and cope with nondeterminate background knowledge. (The only exception is a covering algorithm called FORS.) In this paper we present Structural Regression Trees (SRT), a new algorithm which can be applied to the above class of problems. SRT integrates the statistical method of regression trees into ILP. It constructs a tree containing a literal (an atomic formula or its negation) or a conjunction of literals in each node, and assigns a numerical value to each leaf. SRT provides more comprehensible results than purely statistical methods, and can be applied to a class of problems most other ILP systems cannot handle. Experiments in several real-world domains demonstrate that the approach is competitive with existing methods, indicating that the advantages are not at the expense of predictive accuracy.

  2. Calculating a Stepwise Ridge Regression.

    ERIC Educational Resources Information Center

    Morris, John D.

    1986-01-01

    Although methods for using ordinary least squares regression computer programs to calculate a ridge regression are available, the calculation of a stepwise ridge regression requires a special purpose algorithm and computer program. The correct stepwise ridge regression procedure is given, and a parallel FORTRAN computer program is described.…

  3. Orthogonal Regression: A Teaching Perspective

    ERIC Educational Resources Information Center

    Carr, James R.

    2012-01-01

    A well-known approach to linear least squares regression is that which involves minimizing the sum of squared orthogonal projections of data points onto the best fit line. This form of regression is known as orthogonal regression, and the linear model that it yields is known as the major axis. A similar method, reduced major axis regression, is…

  4. Orthogonal Regression: A Teaching Perspective

    ERIC Educational Resources Information Center

    Carr, James R.

    2012-01-01

    A well-known approach to linear least squares regression is that which involves minimizing the sum of squared orthogonal projections of data points onto the best fit line. This form of regression is known as orthogonal regression, and the linear model that it yields is known as the major axis. A similar method, reduced major axis regression, is…

  5. Characteristics and retention of luteal structures, extended postinsemination cycle, progesterone, and pregnancy-specific protein B in serum after human chorionic gonadotropin treatment of dairy cows.

    PubMed

    Stevenson, J S; Pulley, S L

    2012-08-01

    Our objectives were to determine characteristics (size, number, and stayability) of luteal structures formed in response to human chorionic gonadotropin (hCG) administered on d 7 after timed artificial insemination (AI) and the influence of hCG on returns to estrus and pregnancy outcome. Holstein cows (n=328), milked 3 times daily, previously inseminated at first service were assigned randomly to a completely randomized design consisting of 2 treatments when at least 1 corpus luteum (CL) was detected on d 7 after AI. Treatment consisted of 1,000 IU hCG or 1 mL of saline (control) administered i.m. Blood was collected and luteal structures were mapped and sized by transrectal ultrasonography on d 7, 14, 21, 28, and 32 after AI. Blood also was collected on d 60 in all pregnant cows. Treatment with hCG induced new luteal structures in 70% of cows, regardless of pregnancy status or number of pretreatment CL. Cows producing greater than the median 46 kg of energy-corrected milk per day were less likely to respond to hCG. The number of total luteal structures per cow, original CL volume, and total luteal volume (original CL + new luteal structures) were increased by hCG. Progesterone concentration was greater in pregnant than nonpregnant cows on d 14 unless cows responded to hCG by forming new luteal structures. Concentrations of progesterone were greatest in pregnant, hCG-treated cows. Pregnancy per AI at d 32 or 60 after first AI was less in hCG- than saline-treated cows because pregnancy outcome for hCG cows that had only 1 pretreatment CL and failed to respond to hCG was only 55 to 61% of that observed in controls. Proportions of cows returning to estrus from 18 to 25 d after AI were less in hCG than control cows but greater for cows returning >25 d. Regardless of treatment, 25% of cows in both treatments retained at least 1 original CL to d 28 after AI and were not pregnant on d 32. Progesterone concentrations in these nonpregnant cows with retained CL between d 14

  6. Interferon-related and other immune genes are downregulated in peripheral blood leukocytes in the luteal phase of the menstrual cycle.

    PubMed

    Dosiou, Chrysoula; Lathi, Ruth B; Tulac, Suzana; Huang, S-T Joseph; Giudice, Linda C

    2004-05-01

    Interaction between the endocrine and the immune systems has been suggested by observations of sexual dimorphism of the immune response, differential susceptibility to autoimmunity between the sexes, changes in autoimmune disease activity during the menstrual cycle and in pregnancy and in vitro studies of hormonal influence on cytokine production.We hypothesized that if there is hormonal regulation of the immune response, this would be manifest in peripheral blood leukocytes (PBLs) at different phases of the menstrual cycle. In this study, we describe gene profiling of PBLs from the follicular and luteal phases of the menstrual cycle. We observe important differences in immune gene expression, with significant down-regulation of the Th1 immune response in the luteal phase. A significant number of interferon (IFN)-related genes are amongst the downregulated genes. These results support significant hormonal regulation of the immune system and may have therapeutic implications in diseases of autoimmunity in women.

  7. A case report of an uncommon sex-cord stromal tumor consisted of luteal and sertoli cells in a spayed bitch.

    PubMed

    Ichimura, Ryohei; Shibutani, Makoto; Mizukami, Sayaka; Suzuki, Terumasa; Shimada, Yuko; Mitsumori, Kunitoshi

    2010-02-01

    We report a rare case of benign sex cord-stromal tumor consisted largely of luteoma with minor portion of Sertoli cell tumor located at the position of the left ovary excision in an 11-year-old ovariectomized bitch. Granulosa cell component was lacking, and both luteal and Sertoli cell portions were entirely positive for inhibin alpha and neuron-specific enolase, whereas luteoma portion alone was positive for Wilms' tumor-1 (WT1), immunohistochemically. The results suggest that this tumor is a possible complication of incomplete ovarian excision at the time of ovariectomy and consisted of uncommon hybrid of luteal and Sertoli cells to be diagnosed as an unclassified sex cord-stromal tumor if applied in human cases. WT1-expression pattern suggested the signature of the difference in the phenotype of these cell types.

  8. The effect of luteal-phase support with vaginal progesterone on pregnancy rates in gonadotropin and clomiphene citrate/intra-uterine insemination cycles in unexplained infertility: A prospective randomised study.

    PubMed

    Karadag, Burak; Dilbaz, Berna; Karcaaltincaba, Deniz; Sahin, Elif Gulsah; Ercan, Fedi; Karasu, Yetkin; Tonyalı, Nazan Vanlı

    2016-08-01

    The purpose of this study is to analyse the effect of luteal-phase support on pregnancy rates in gonadotropin + intra-uterine insemination (Gn/IUI) and clomiphene citrate (CC) +IUI (CC/IUI) cycles in patients with unexplained infertility. Equal numbers of patients were recruited in two treatment arms (CC/IUI and Gn/IUI) (n = 100, n = 100, respectively). In each group, 50 patients received vaginal progesterone for 14 days (Crinone 8% vaginal gel, 90 mg per day) for luteal-phase support from the day after IUI and continued until menstruation or the 10th week of gestation if pregnant. There were 29 clinical pregnancies among 200 patients. Pregnancy rates were 12% in CC/IUI cycles, 10% in luteal-phase-supported CC/IUI cycles 16% in Gn/IUI cycles and 20% in luteal-phase-supported Gn/IUI cycles. Although pregnancy rates were higher in Gn/IUI cycles compared to CC/IUI cycles, luteal-phase support did not significantly affect the pregnancy rates in both groups. This study implies that luteal-phase support with progesterone has no pronounced beneficial effect on pregnancy rates in either CC/IUI or Gn/IUI cycles in patients with unexplained infertility.

  9. The Effects of Smoked Nicotine on Measures of Subjective states and Hypothalamic-Pituitary-Adrenal Axis Hormones in Women during the Follicular and Luteal Phases of the Menstrual Cycle

    PubMed Central

    Goletiani, Nathalie V.; Siegel, Arthur J.; Lukas, Scott E.; Hudson, James I.

    2015-01-01

    Objectives To determine the acute effects of cigarette smoking on hypothalamic-pituitary-adrenal axis (HPA) hormones and subjective states as a function of the menstrual cycle in nicotine-dependent women. Methods Seventeen healthy nicotine-dependent women were studied during the follicular and/or luteal phase of the menstrual cycle. Due to observation of a possible bimodal distribution of progesterone levels within the luteal phase group, we performed a set of a posteriori analyses. Therefore, we divided the luteal group into a low progesterone and a high progesterone groups. Results Smoked nicotine activated HPA, measured by ACTH, cortisol, and DHEA response and affected subjective states in both follicular and luteal phases, with increased “High”, “Rush”, and decreased “Craving”. The HPA stimulation revealed a blunting of ACTH response. There was only modest evidence for a blunting of subjective state responses in the luteal phase. However upon post hoc analyses, the high progesterone luteal group showed a marked blunting of measures of subjective states and a blunted ACTH response. Examining the association between hormone and measures of subjective states revealed tentative associations of ACTH stimulation with increased “Rush” and “Craving”, and DHEA stimulation with increased “Craving”. Conclusions This pilot study suggests that menstrual cycle phase differences in progesterone levels may attenuate nicotine’s addictive effects via diminution of its reinforcing properties, and augmentation of its aversive effects interfering with the pleasure associated with cigarette smoking. PMID:25783522

  10. Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support—Results of a Prospective, Randomized, Comparative Study

    PubMed Central

    Pirard, Céline; Loumaye, Ernest; Wyns, Christine

    2015-01-01

    Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols. PMID:25945092

  11. Modified Regression Correlation Coefficient for Poisson Regression Model

    NASA Astrophysics Data System (ADS)

    Kaengthong, Nattacha; Domthong, Uthumporn

    2017-09-01

    This study gives attention to indicators in predictive power of the Generalized Linear Model (GLM) which are widely used; however, often having some restrictions. We are interested in regression correlation coefficient for a Poisson regression model. This is a measure of predictive power, and defined by the relationship between the dependent variable (Y) and the expected value of the dependent variable given the independent variables [E(Y|X)] for the Poisson regression model. The dependent variable is distributed as Poisson. The purpose of this research was modifying regression correlation coefficient for Poisson regression model. We also compare the proposed modified regression correlation coefficient with the traditional regression correlation coefficient in the case of two or more independent variables, and having multicollinearity in independent variables. The result shows that the proposed regression correlation coefficient is better than the traditional regression correlation coefficient based on Bias and the Root Mean Square Error (RMSE).

  12. Ridge regression processing

    NASA Technical Reports Server (NTRS)

    Kuhl, Mark R.

    1990-01-01

    Current navigation requirements depend on a geometric dilution of precision (GDOP) criterion. As long as the GDOP stays below a specific value, navigation requirements are met. The GDOP will exceed the specified value when the measurement geometry becomes too collinear. A new signal processing technique, called Ridge Regression Processing, can reduce the effects of nearly collinear measurement geometry; thereby reducing the inflation of the measurement errors. It is shown that the Ridge signal processor gives a consistently better mean squared error (MSE) in position than the Ordinary Least Mean Squares (OLS) estimator. The applicability of this technique is currently being investigated to improve the following areas: receiver autonomous integrity monitoring (RAIM), coverage requirements, availability requirements, and precision approaches.

  13. Overexpression of cellular repressor of E1A-stimulated genes inhibits TNF-{alpha}-induced apoptosis via NF-{kappa}B in mesenchymal stem cells

    SciTech Connect

    Peng, Cheng-Fei; Han, Ya-Ling; Jie-Deng,; Yan, Cheng-Hui; Jian-Kang,; Bo-Luan,; Jie-Li

    2011-03-25

    Research highlights: {yields} CREG protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis. {yields} CREG inhibits the phosphorylation of I{kappa}B{alpha} and prevents the activation of NF-{kappa}B. {yields} CREG inhibits NF-{kappa}B nuclear translocation and pro-apoptosis protein transcription. {yields} CREG anti-apoptotic effect involves inhibition of the death receptor pathway. {yields} p53 is downregulated by CREG via NF-{kappa}B pathway under TNF-{alpha} stimulation. -- Abstract: Bone marrow-derived mesenchymal stem cells (MSCs) show great potential for therapeutic repair after myocardial infarction. However, poor viability of transplanted MSCs in the ischemic heart has limited their use. Cellular repressor of E1A-stimulated genes (CREG) has been identified as a potent inhibitor of apoptosis. This study therefore aimed to determine if rat bone marrow MSCs transfected with CREG-were able to effectively resist apoptosis induced by inflammatory mediators, and to demonstrate the mechanism of CREG action. Apoptosis was determined by flow cytometric and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays. The pathways mediating these apoptotic effects were investigated by Western blotting. Overexpression of CREG markedly protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis by 50% after 10 h, through inhibition of the death-receptor-mediated apoptotic pathway, leading to attenuation of caspase-8 and caspase-3. Moreover, CREG resisted the serine phosphorylation of I{kappa}B{alpha} and prevented the nuclear translocation of the transcription factor nuclear factor-{kappa}B (NF-{kappa}B) under TNF-{alpha} stimulation. Treatment of cells with the NF-{kappa}B inhibitor pyrrolidine dithiocarbamate (PDTC) significantly increased the transcription of pro-apoptosis proteins (p53 and Fas) by NF-{kappa}B, and attenuated the anti-apoptotic effects of CREG on MSCs. The results of this study

  14. Experimental study on inhibitory effect of niacinamide on tumor necrosis factor-alpha-induced matrix degradation of annulus fibrous tissue in vitro.

    PubMed

    Xu, Runbing; Shao, Zengwu; Xiong, Liming

    2008-10-01

    The inhibitory effect of niacinamide on tumor necrosis factor-alpha (TNF-alpha) induced annulus fibrous (AF) degradation was assessed, and the mechanism of the inhibition was investigated. Chiba's intervertebral disc (IVD) culture model was established. Forty-eight IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups (12 IVDs in each group), and various concentrations of niacinamide and TNF-alpha were added to the medium for intervention: negative control group, niacinamide control group (0.5 mg/mL niacinamide), degeneration group (10 ng/mL TNF-alpha), and treatment group (0.5 mg/mL niacinamide and 10 ng/mL TNF-alpha). After one week's culture, AFs were collected for glycosaminoglycan (GS) content measurement, safranin O-fast green staining, and immunohistochemical staining for type I, II collagen and cysteine containing aspartate specific protease-3 (Caspase-3). It was found that the GS content in treatment group was increased by about 48% as compared with degeneration group (t=16.93, P<0.001), and close to that in niacinamide control group (t=0.71, P=0.667). Safranine O-fast green staining exhibited higher staining density and better histological structure of AF in the treatment group as compared with the degeneration group. Immunohistochemical staining for both Type I and II collagen demonstrated that lamellar structure and continuity of collagen in treatment group were better reserved than in degeneration group. Positive staining rate of Caspase-3 in AFs of negative control group, niacinamide control group, degeneration group and treatment group was 3.4%, 4.3%, 17.9% and 10.3% respectively. The positive rate in treatment group was significantly lower than in degeneration group (P<0.01). It was concluded that niacinamide could effectively alleviate TNF-alpha induced destruction and synthesis inhibition of matrix ingredients in AFs. The inhibition may be related with reduction of expression of Caspase-3. Thus, niacinamide is of potential

  15. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    SciTech Connect

    Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  16. Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-{alpha}-induced NF-{kappa}B activity by binding to TNFR1

    SciTech Connect

    Hwang, Jae Ryoung; Huh, Jae Ho; Lee, Yoonna; Lee, Sang Il; Rho, Seung Bae; Lee, Je-Ho

    2011-02-25

    Research highlights: {yields} Binding assays demonstrated that secreted- and cellular-IGFBP-5 interacted with TNFR1. {yields} The interaction between IGFBP-5 and TNFR1 was inhibited by TNF-{alpha} and was blocked TNF-{alpha}-activated NF-{kappa}B activity. {yields} IGFBP-5 interacted with TNFR1 through its N- and L-domains but the binding of L-domain to TNFR1 was blocked by TNF-{alpha}. {yields} Competition between the L-domain of IGFBP-5 and TNF-{alpha} blocked TNF-{alpha}-induced NF-{kappa}B activity. {yields} This study suggests that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor. -- Abstract: IGFBP-5 is known to be involved in various cell phenomena such as proliferation, differentiation, and apoptosis. However, the exact mechanisms by which IGFBP-5 exerts its functions are unclear. In this study, we demonstrate for the first time that IGFBP-5 is a TNFR1-interacting protein. We found that ectopic expression of IGFBP-5 induced TNFR1 gene expression, and that IGFBP-5 interacted with TNFR1 in both an in vivo and an in vitro system. Secreted IGFBP-5 interacted with GST-TNFR1 and this interaction was blocked by TNF-{alpha}, demonstrating that IGFBP-5 might be a TNFR1 ligand. Furthermore, conditioned media containing secreted IGFBP-5 inhibited PMA-induced NF-{kappa}B activity and IL-6 expression in U-937 cells. Coimmunoprecipitation assays of TNFR1 and IGFBP-5 wild-type and truncation mutants revealed that IGFBP-5 interacts with TNFR1 through its N- and L-domains. However, only the interaction between the L-domain of IGFBP-5 and TNFR1 was blocked by TNF-{alpha} in a dose-dependent manner, suggesting that the L-domain of IGFBP-5 can function as a TNFR1 ligand. Competition between the L-domain of IGFBP-5 and TNF-{alpha} resulted in inhibition of TNF-{alpha}-induced NF-{kappa}{Beta} activity. Taken together, our results suggest that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF

  17. Luteal phase support with estrogen in addition to progesterone increases pregnancy rates in in vitro fertilization cycles with poor response to gonadotropins.

    PubMed

    Kutlusoy, Fatma; Guler, Ismail; Erdem, Mehmet; Erdem, Ahmet; Bozkurt, Nuray; Biberoglu, Ebru H; Biberoglu, Kutay O

    2014-05-01

    In this study, our objective was to determine the effect of adding estradiol hemihydrate (E2) to progestin (P) for luteal phase support on pregnancy outcome in in vitro fertilization (IVF) cycles with poor response to gonadotropins. Ninety-five women with poor ovarian response who underwent controlled ovarian hyperstimulation (COH) with gonadotropin releasing hormone (GnRH) agonist or GnRH antagonist plus gonadotropin protocol for IVF were prospectively randomized into three groups of luteal phase support after oocyte retrieval. Group 1 (n = 33) received only intravaginal progesterone gel (Crinone 8% gel). Group 2 (n = 27) and Group 3 (n = 35) received intravaginal progesterone plus oral 2 and 6 mg estradiol hemihydrate, respectively. Main outcome measures were overall and clinical pregnancy rates (PRs) per patient. Serum LH, E2 and P levels at 7th and 14th days of luteal phase were also measured. Overall and clinical PRs were significantly higher in 2 mg E2 + P than P-only group (44% versus 18% and 37% versus 12.1%, respectively). There were no statistically significant differences between 6 mg E2 + P versus P-only and 2 mg E2 + P versus 6 mg E2 + P groups regarding PRs. Addition of 2 mg/day E2 in addition to P for luteal support significantly increase overall and clinical PRs in cycles with poor response to gonadotropins after IVF.

  18. Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells.

    PubMed

    Liu, Jianqi; Kuulasmaa, Tiina; Kosma, Veli-Matti; Bützow, Ralf; Vänttinen, Teemu; Hydén-Granskog, Christel; Voutilainen, Raimo

    2003-10-01

    Activins and inhibins are often antagonistic in the regulation of ovarian function. TGFbeta type III receptor, betaglycan, has been identified as a coreceptor to enhance the binding of inhibins to activin type II receptor and thus to prevent the binding of activins to their receptor. In this study we characterized the expression and regulation pattern of betaglycan gene in normal ovaries and sex cord-stromal tumors and in cultured human granulosa-luteal cells from women undergoing in vitro fertilization. Expression of betaglycan mRNA was detected by RT-PCR or Northern blotting in normal ovarian granulosa, thecal, and stroma cells as well as in granulosa-luteal cells. Immunohistochemical analysis revealed positive staining for betaglycan in antral and preovulatory follicular granulosa and thecal cells and in corpora lutea of normal ovaries. Furthermore, betaglycan expression was detected in the vast majority of granulosa cell tumors, thecomas, and fibromas, with weaker staining in granulosa cell tumors compared with fibrothecomas. In cultured granulosa-luteal cells, FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA, as did the protein kinase A activator dibutyryl cAMP and the protein kinase C inhibitor staurosporine. In contrast, the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate had no significant effect on betaglycan mRNA levels. Treatment with prostaglandin E(2) and with its receptor EP2 subtype agonist butaprost increased betaglycan mRNA accumulation and progesterone secretion dose- and time-dependently. In summary, betaglycan gene is expressed in normal human ovarian steroidogenic cells and sex cord-stromal ovarian tumors. The accumulation of its mRNA in cultured granulosa-luteal cells is up-regulated by gonadotropins and prostaglandin E(2), probably via the protein kinase A pathway. The specific expression and regulation pattern of betaglycan gene may be related to the functional antagonism of inhibins to

  19. 5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder.

    PubMed

    Martinez, Pedro E; Rubinow, David R; Nieman, Lynnette K; Koziol, Deloris E; Morrow, A Leslie; Schiller, Crystal E; Cintron, Dahima; Thompson, Karla D; Khine, Khursheed K; Schmidt, Peter J

    2016-03-01

    Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data

  20. Steady-state concentrations of mRNA encoding two inhibitors of protein kinase C in ovine luteal tissue.

    PubMed

    Juengel, J L; Melner, M H; Clapper, J A; Turzillo, A M; Moss, G E; Nett, T M; Niswender, G D

    1998-07-01

    Prostaglandin F2 alpha (PGF2 alpha) decreases secretion of progesterone from the corpus luteum in domestic ruminants. However, it is less effective during the early part of the oestrous cycle (Louis et al., 1973) and at the time of maternal recognition of pregnancy (Silvia and Niswender, 1984; Lacroix and Kann, 1986). Decreased luteal responsiveness may be due to failure of PGF2 alpha to activate fully its normal second messenger system, protein kinase C (PKC). Alternatively, increased resistance of the corpus luteum to PGF2 alpha might be attributable to greater concentrations of recently identified biological inhibitors of PKC. These possibilities were addressed by measuring steady-state concentrations of mRNA encoding PGF2 alpha receptor and two inhibitors of PKC, protein kinase C inhibitor-1 (PKCI-1) and kinase C inhibitor protein-1 (KCIP-1, brain 14-3-3 protein), in corpora lutea collected from ewes on days 4, 10 and 15 of the oestrous cycle (n = 5 per day) and day 15 of pregnancy (n = 7). There were no differences in mean concentrations of mRNA encoding PGF2 alpha receptor among the groups. However, concentrations of mRNA encoding both inhibitors of PKC were higher (P < 0.01) on day 4 of the oestrous cycle compared with the other groups. Treatment of ewes with a luteolytic dose of PGF2 alpha, which activates PKC, did not change concentrations of mRNA encoding either PKCI-1 or KCIP-I up to 24 h later. Luteal expression of mRNA encoding the PKC inhibitors and PGF2 alpha receptor was also examined in ewes treated with oestradiol in vivo for 16 h in the midluteal phase. High concentrations of oestradiol in serum (20 and 70 pg ml-1) did not influence quantities of any of the mRNAs examined. Therefore, an increase in PKC inhibitors may be involved in resistance of the corpus luteum to PGF2 alpha during the early part of the oestrous cycle but does not appear to mediate the increased resistance of the corpus luteum to PGF2 alpha during maternal recognition of

  1. Vaginal (Crinone 8%) gel vs. intramuscular progesterone in oil for luteal phase support in in vitro fertilization: a large prospective trial.

    PubMed

    Silverberg, Kaylen M; Vaughn, Thomas C; Hansard, Lisa J; Burger, Natalie Z; Minter, Tamara

    2012-02-01

    To compare the efficacy of intravaginal and IMP for luteal phase support in IVF cycles. Prospective trial. Tertiary care private practice. Women 25-44 years old with infertility necessitating treatment with IVF. From April 1, 2008-April 1, 2009, 511 consecutive patients were enrolled; 474 completed participation, and 37 were excluded for no autologous ET (freeze all, donor recipients, failed fertilization/cleavage). There were no demographic differences between the two treatment groups. Luteal phase support using either Crinone or P in oil starting 2 days following oocyte retrieval. Pregnancy and delivery rates stratified by patient age. Overall, patients who received vaginal P had higher pregnancy (70.9% vs. 64.2%) and delivery (51.7% vs. 45.4%) rates than did patients who received IMP. Patients <35 who received vaginal P had significantly higher delivery rates (65.7% vs. 51.1%) than did patients who received IMP. There were no differences, regardless of age, in the rates of biochemical pregnancy, miscarriage, or ectopics. In younger patients undergoing IVF, support of the luteal phase with Crinone produces significantly higher pregnancy rates than does IMP. Crinone and IMP appear to be equally efficacious in the older patient. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Day two post retrieval 1500 IUI hCG bolus, progesterone-free luteal support post GnRH agonist trigger - a proof of concept study.

    PubMed

    Vanetik, Sharon; Segal, Linoy; Breizman, Tatiana; Kol, Shahar

    2017-09-21

    Small dose of hCG (1500 IU) on the day of oocyte retrieval, followed by daily progesterone administration, is currently the preferred way to secure adequate luteal support following GnRH agonist trigger. In the current proof-of-concept study, we explored the possibility that a bolus of 1500 IU hCG, given two days after oocyte retrieval, may be sufficient to sustain adequate luteal support without additional progesterone treatment. From February 2015 to August 2016, we obtained 44 pregnancies following GnRHa trigger followed by day 2 hCG (1500 IU) support only (study group). Data from these 44 cycles were compared with the latest 44 pregnancies obtained following hCG (6500 IU) trigger followed by conventional progesterone luteal documented (control group). Mean progesterone levels (14 days postoocyte retrieval) in the study and control groups were 197 nmol/l and 173 nmol/l, respectively (NS). Mean E2 levels (14 days post oocyte retrieval) in the study group was 6937 pmol/l, significantly higher (p < .001) than in the control group (3.276 pmol/l). We conclude that bolus of 1500 IU hCG, administered 2 days after retrieval, can provide excellent support, without the need to further supplement with progesterone.

  3. Ultrastructural and biochemical evidence for the presence of mature steroidogenic acute regulatory protein (StAR) in the cytoplasm of human luteal cells.

    PubMed

    Sierralta, Walter D; Kohen, Paulina; Castro, Olga; Muñoz, Alex; Strauss, Jerome F; Devoto, Luigi

    2005-10-20

    The distribution of the steroidogenic acute regulatory protein (StAR) inside thecal and granulosa-lutein cells of human corpus luteum (CL) was assessed by immunoelectron microscopy. We found greater levels of StAR immunolabeling in steroidogenic cells from early- and mid-than in late luteal phase CL and lower levels in cells from women treated with a GnRH antagonist in the mid-luteal phase. Immunoelectron microscopy revealed significant levels of StAR antigen in the mitochondria and in the cytoplasm of luteal cells. The 30 kDa mature StAR protein was present in both mitochondria and cytosol (post-mitochondrial) fractions from homogenates of CL at different ages, whereas cytochrome c and mitochondrial HSP70 were detected only in the mitochondrial fraction. Therefore, we hypothesized that either appreciable processing of StAR 37 kDa pre-protein occurs outside the mitochondria, or mature StAR protein is selectively released into the cytoplasm after mitochondrial processing. The presence of mature StAR in the cytoplasm is consonant with the notion that StAR acts on the outer mitochondrial membrane to effect sterol import, and that StAR may interact with other cytoplasmic proteins involved in cholesterol metabolism, including hormone sensitive lipase.

  4. Tumor necrosis factor-alpha induces apoptosis associated with poly(ADP-ribose) polymerase cleavage in HT-29 colon cancer cells.

    PubMed

    Vaculová, Alena; Hofmanova, Jirina; Soucek, Karel; Kovariková, Martina; Kozubík, Alois

    2002-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is known for its selective cytotoxic activity on tumour cells. We analysed the response of HT-29 human colon carcinoma cells to this cytokine. After TNF-alpha treatment, cell proliferation, cell cycle, reactive oxygen species (ROS) production (flow cytometry), the amount of apoptotic cells (flow cytometry, fluorescence microscopy), cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3 activity (Western blotting) were detected. TNF-alpha induced a decrease of cell growth and viability, an accumulation of cells in the S-phase of the cell cycle, an increase of subdiploid cell population and nuclear chromatin condensation and fragmentation, but not sooner than 96-120 hours. However, earlier events characteristic of apoptosis occurred, such as caspase-3 activation, PARP cleavage to 89 kDa fragment and changes in ROS production. We demonstrated that, in addition to being an early marker of apoptosis, activation of caspase-3 and degradation of PARP may play a causative role in HT-29 cell death induced by TNF-alpha.

  5. TNF{alpha} induced FOXP3-NF{kappa}B interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells

    SciTech Connect

    Hao, Qiang; Li, Weina; Zhang, Cun; Qin, Xin; Xue, Xiaochang; Li, Meng; Shu, Zhen; Xu, Tianjiao; Xu, Yujin; Wang, Weihua; Zhang, Wei; Zhang, Yingqi

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer FOXP3 inhibition of cell proliferation is p21-dependent under basal conditions. Black-Right-Pointing-Pointer Inflammation induced by TNF{alpha} inhibits the tumor suppressor role of FOXP3. Black-Right-Pointing-Pointer Interaction between p65 and FOXP3 inhibits p21 transcription activation. -- Abstract: Controversial roles of FOXP3 in different cancers have been reported previously, while its role in gastric cancer is largely unknown. Here we found that FOXP3 is unexpectedly upregulated in some gastric cancer cells. To test whether increased FOXP3 remains the tumor suppressor role in gastric cancer as seen in other cancers, we test its function in cell proliferation both at basal and TNF{alpha} mimicked inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNF{alpha} treatment. Molecularly, we found that TNF{alpha} induced an interaction between FOXP3 and p65, which in turn drive the FOXP3 away from the promoter of the well known target p21. Our data here suggest that although FOXP3 is upregulated in gastric cancer, its tumor suppressor role has been dampened due to the inflammation environment.

  6. Production of A=16, 20 and 24 in alpha-induced fragmentation of ^28Si at 102.7 (cm) MeV

    NASA Astrophysics Data System (ADS)

    Sabra, Mohammad S.; Bary Malik, F.

    2004-10-01

    The emission probabilities of particles of mass numbers 16, 20 and 24 in 102.7 (cm) MeV alpha-induced fragmentation of ^28Si have been calculated using the statistical model of [1]. This model is distinct from the usual evaporation model in the sense that it takes into account the final state interaction between two emerging fragments. Calculated emission probabilities indicate that particles are emitted in all possible excited states commensurate with energy conservation law. The emission spectra as a function of excitation energy and the most probable kinetic energy associated with it will be presented. Calculated differential cross sections at 30^o for these masses are in agreement with the data of [2]. The final state interaction is obtained by a scaling procedure. The emission probabilities of different isotopes of these masses will also be presented. 1. B. Compani-Tabrizi and F. B. Malik, J. Phys. G: Nucl. Phys. 8, 1447 (1982). 2. L. W. Woo et al. Phys. Rev. C 47, 267 (1993).

  7. Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus.

    PubMed

    Garcia, J A; Ferreira, H L; Vieira, F V; Gameiro, R; Andrade, A L; Eugênio, F R; Flores, E F; Cardoso, T C

    2015-09-16

    Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication-induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy.

  8. Manassantin A and B isolated from Saururus chinensis inhibit TNF-alpha-induced cell adhesion molecule expression of human umbilical vein endothelial cells.

    PubMed

    Kwon, Oh Eok; Lee, Hyun Sun; Lee, Seung Woong; Chung, Mi Yeon; Bae, Ki Hwan; Rho, Mun-Chual; Kim, Young-Kook

    2005-01-01

    Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.

  9. Modulation of the noradrenergic activity index by neural stimulus, and its participation in ovarian androstenedione release during the luteal phase.

    PubMed

    Bronzi, Daniela; Orozco, Adriana Vega; Delgado, Silvia Marcela; Casais, Marilina; Rastrilla, Ana M; Sosa, Zulema Y

    2011-03-15

    To investigate the participation of catecholamines in the association between peripheral innervation and luteal steroidogenesis. Animal study. University animal laboratory. Six to eight virgin adult Holtzman-strain female rats in control and experimental groups on diestrus days 1 and 2. Removal of the coeliac ganglion-superior ovarian nerve-ovary system, with catecholaminergic agonist or antagonist added in the ganglion compartment (experimental group only). The control group received no treatment. Ovarian neurotransmitters and their catabolites measured by reverse-phase high-pressure liquid chromatography, and A(2) measured by radioimmunoassay. On day 1, dopamine and catabolite increased whereas norepinephrine decreased, and the noradrenergic neuronal activity index was higher. On day 2, dopamine levels decreased, norepinephrine increased, and dopaminergic neuronal activity was higher. The release of A(2) was decreased by addition of norepinephrine to the ganglions on day 1, but was increased by the norepinephrine antagonist on day 2. Hence, norepinephrine increased A(2) release, and propranolol diminished it. Ganglionic activity is modified by noradrenergic stimulus, leading to different ovarian A(2) release profiles. The peripheral nervous system is a modulator in these homeostatic mechanisms. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Reduced Phase-Advance of Plasma Melatonin after Bright Morning Light in the Luteal, but not Follicular, Menstrual Cycle Phase in Premenstrual Dysphoric Disorder: An Extended Study

    PubMed Central

    Parry, Barbara L.; Meliska, Charles J.; Sorenson, Diane L.; Martínez, L. Fernando; López, Ana M.; Elliott, Jeffrey A.; Hauger, Richard L.

    2011-01-01

    We previously observed blunted phase-shift responses to morning bright light in women with Premenstrual Dysphoric Disorder (PMDD). The aim of this study was to determine if we could replicate these findings using a higher intensity, shorter duration light pulse and to compare these results with the effects of an evening bright light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, we measured plasma melatonin at 30 minute intervals from 18:00–10:00 h in dim (< 30 lux) or dark conditions the night before (night 1) and after (night 3) a bright light pulse (administered on night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3,000 lux for 6 h or 6,000 lux for 3 h) was given either in the AM, 7 h after the Dim Light Melatonin Onset (DLMO) measured the previous month, or in the PM, 3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between night 1 and night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak or area under the curve. These findings replicated our previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6,000 vs. 3,000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal phase subsensitivity or an increased resistance to morning bright light cues which are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD. PMID:21721857

  11. [Caudal regression syndrome].

    PubMed

    Hortelano, M; Palencia, J; García, J; Reig, C; Herrera, M; Romero, M D; Cuadrado, P

    1998-10-01

    The regression caudal syndrome includes a spectrum of malformations which vary from the symptomless coccygeal agenesis until thoracic vertebrae and sacrococcygeal agenesis with severe neurological deficit; it is associated sometimes with malformations in other organs and systems. We present a case of partial agenesis of sacro and coccix with neuromuscular, sphincter and orthopedist alterations. A 4-year-old patient consults because of walk alterations, with daytime and nocturnal enuresis and urinary incontinence, constipation/encopresis and rectal prolapse. Familiar and personnel precedents are uninteresting. She began to walk at normal age, referring only rectal prolapse with constipation from nursing and urinary tract infections and encopresis when she was 3 years old, with normal complementary explorations (digestive and nephrourologyc). She presents in lumbosacral X-rays four lumbar vertebrae, a dysplasic sacro and absence of coccix. Hypoplasy of sacro with bilateral stenosis of the pelvis and coxa vara in both femurs are seen in the lumbar CT. In RMI is observed agenesis of sacro and coccix vertebrae. There are a wide variety of sacrococcygeal agenesis, which are classified by Renshaw and modified by Pang. As etiologics factors we find the gestational diabetes, in addition to genetic factors. The clinic exploration guides us toward a flaccid paraparesia/areflexia, with orthopaedist alterations, sometimes of artrogripotyc type. With image techniques (X-rays, CT, MRI) we can accomplish the diagnosis and we can discard or demonstrate associated medullary anomalies. We concluded that in all patient with alterations of walk and/or lack of sphincters control we should explore the lumbosacral region searching for medulodiysplasic or vertebral alterations.

  12. Recursive Algorithm For Linear Regression

    NASA Technical Reports Server (NTRS)

    Varanasi, S. V.

    1988-01-01

    Order of model determined easily. Linear-regression algorithhm includes recursive equations for coefficients of model of increased order. Algorithm eliminates duplicative calculations, facilitates search for minimum order of linear-regression model fitting set of data satisfactory.

  13. Fluid shear stress inhibits TNF-alpha-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3

    NASA Technical Reports Server (NTRS)

    Pavalko, Fredrick M.; Gerard, Rita L.; Ponik, Suzanne M.; Gallagher, Patricia J.; Jin, Yijun; Norvell, Suzanne M.

    2003-01-01

    In bone, a large proportion of osteoblasts, the cells responsible for deposition of new bone, normally undergo programmed cell death (apoptosis). Because mechanical loading of bone increases the rate of new bone formation, we hypothesized that mechanical stimulation of osteoblasts might increase their survival. To test this hypothesis, we investigated the effects of fluid shear stress (FSS) on osteoblast apoptosis using three osteoblast cell types: primary rat calvarial osteoblasts (RCOB), MC3T3-E1 osteoblastic cells, and UMR106 osteosarcoma cells. Cells were treated with TNF-alpha in the presence of cyclohexamide (CHX) to rapidly induce apoptosis. Osteoblasts showed significant signs of apoptosis within 4-6 h of exposure to TNF-alpha and CHX, and application of FSS (12 dyne/cm(2)) significantly attenuated this TNF-alpha-induced apoptosis. FSS activated PI3-kinase signaling, induced phosphorylation of Akt, and inhibited TNF-alpha-induced activation of caspase-3. Inhibition of PI3-kinase, using LY294002, blocked the ability of FSS to rescue osteoblasts from TNF-alpha-induced apoptosis and blocked FSS-induced inhibition of caspase-3 activation in osteoblasts treated with TNF-alpha. LY294002 did not, however, prevent FSS-induced phosphorylation of Akt suggesting that activation of Akt alone is not sufficient to rescue cells from apoptosis. This result also suggests that FSS can activate Akt via a PI3-kinase-independent pathway. These studies demonstrate for the first time that application of FSS to osteoblasts in vitro results in inhibition of TNF-alpha-induced apoptosis through a mechanism involving activation of PI3-kinase signaling and inhibition of caspases. FSS-induced activation of PI3-kinase may promote cell survival through a mechanism that is distinct from the Akt-mediated survival pathway. Copyright 2002 Wiley-Liss, Inc.

  14. Fluid shear stress inhibits TNF-alpha-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3

    NASA Technical Reports Server (NTRS)

    Pavalko, Fredrick M.; Gerard, Rita L.; Ponik, Suzanne M.; Gallagher, Patricia J.; Jin, Yijun; Norvell, Suzanne M.

    2003-01-01

    In bone, a large proportion of osteoblasts, the cells responsible for deposition of new bone, normally undergo programmed cell death (apoptosis). Because mechanical loading of bone increases the rate of new bone formation, we hypothesized that mechanical stimulation of osteoblasts might increase their survival. To test this hypothesis, we investigated the effects of fluid shear stress (FSS) on osteoblast apoptosis using three osteoblast cell types: primary rat calvarial osteoblasts (RCOB), MC3T3-E1 osteoblastic cells, and UMR106 osteosarcoma cells. Cells were treated with TNF-alpha in the presence of cyclohexamide (CHX) to rapidly induce apoptosis. Osteoblasts showed significant signs of apoptosis within 4-6 h of exposure to TNF-alpha and CHX, and application of FSS (12 dyne/cm(2)) significantly attenuated this TNF-alpha-induced apoptosis. FSS activated PI3-kinase signaling, induced phosphorylation of Akt, and inhibited TNF-alpha-induced activation of caspase-3. Inhibition of PI3-kinase, using LY294002, blocked the ability of FSS to rescue osteoblasts from TNF-alpha-induced apoptosis and blocked FSS-induced inhibition of caspase-3 activation in osteoblasts treated with TNF-alpha. LY294002 did not, however, prevent FSS-induced phosphorylation of Akt suggesting that activation of Akt alone is not sufficient to rescue cells from apoptosis. This result also suggests that FSS can activate Akt via a PI3-kinase-independent pathway. These studies demonstrate for the first time that application of FSS to osteoblasts in vitro results in inhibition of TNF-alpha-induced apoptosis through a mechanism involving activation of PI3-kinase signaling and inhibition of caspases. FSS-induced activation of PI3-kinase may promote cell survival through a mechanism that is distinct from the Akt-mediated survival pathway. Copyright 2002 Wiley-Liss, Inc.

  15. Linear regression in astronomy. I

    NASA Technical Reports Server (NTRS)

    Isobe, Takashi; Feigelson, Eric D.; Akritas, Michael G.; Babu, Gutti Jogesh

    1990-01-01

    Five methods for obtaining linear regression fits to bivariate data with unknown or insignificant measurement errors are discussed: ordinary least-squares (OLS) regression of Y on X, OLS regression of X on Y, the bisector of the two OLS lines, orthogonal regression, and 'reduced major-axis' regression. These methods have been used by various researchers in observational astronomy, most importantly in cosmic distance scale applications. Formulas for calculating the slope and intercept coefficients and their uncertainties are given for all the methods, including a new general form of the OLS variance estimates. The accuracy of the formulas was confirmed using numerical simulations. The applicability of the procedures is discussed with respect to their mathematical properties, the nature of the astronomical data under consideration, and the scientific purpose of the regression. It is found that, for problems needing symmetrical treatment of the variables, the OLS bisector performs significantly better than orthogonal or reduced major-axis regression.

  16. Evaluating differential effects using regression interactions and regression mixture models

    PubMed Central

    Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This paper focuses on understanding regression mixture models, a relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their formulation, and their assumptions are compared using Monte Carlo simulations and real data analysis. The capabilities of regression mixture models are described and specific issues to be addressed when conducting regression mixtures are proposed. The paper aims to clarify the role that regression mixtures can take in the estimation of differential effects and increase awareness of the benefits and potential pitfalls of this approach. Regression mixture models are shown to be a potentially effective exploratory method for finding differential effects when these effects can be defined by a small number of classes of respondents who share a typical relationship between a predictor and an outcome. It is also shown that the comparison between regression mixture models and interactions becomes substantially more complex as the number of classes increases. It is argued that regression interactions are well suited for direct tests of specific hypotheses about differential effects and regression mixtures provide a useful approach for exploring effect heterogeneity given adequate samples and study design. PMID:26556903

  17. A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles.

    PubMed

    Saharkhiz, Nasrin; Zamaniyan, Marzieh; Salehpour, Saghar; Zadehmodarres, Shahrzad; Hoseini, Sedighe; Cheraghi, Leila; Seif, Samira; Baheiraei, Nafiseh

    2016-01-01

    The aim of the present study was to compare the efficacy, tolerability and patients' satisfaction after the use of oral dydrogesterone with vaginal micronized progesterone for luteal-phase support (LPS) among infertile women undergoing in vitro fertilization (IVF). A total of 210 women (aged 20-40 years old) with a history of infertility, who underwent controlled ovarian stimulation for fresh intra-cytoplasmic sperm injection-embryo transfer cycles, were included in the study. Consequently, they were randomized to receive LPS with dydrogesterone 20 mg twice daily (n = 96) or micronized progesterone 400 mg twice daily at the day of oocyte retrieval (n = 114). The clinical success rate (31% versus 33%; p = 0.888), miscarriage rate (5.0% versus 3.0%; p = 0.721), ongoing pregnancy rate (30.0% versus 30.0%; p = 1.000), implantation (22.0% versus 24.0%; p = 0.254) and multiple pregnancy rate (5.30% versus 7.20%; p = 0.394) were comparable among the two groups. Serum progesterone levels were significantly lower among the patients receiving dydrogesterone than the control group (13.62 ± 13.83 ng/ml versus 20.66 ± 18.09 ng/ml; p = 0.001). However, there was no statistically significant difference regarding the patients' satisfaction (p = 0.825) and tolerability (0.790) between the two groups. Our results showed that oral dydrogesterone (40 mg/day) is as effective as vaginal micronized progesterone considering its clinical outcomes and patients' satisfaction and tolerability, for LPS among women undergoing IVF.

  18. Reproductive physiology of the female greater bilby (Macrotis lagotis Thylacomyidae): evidence for a male-induced luteal phase.

    PubMed

    Ballantyne, K; Matson, P; Noakes, N; Nicolson, V; Johnston, S D

    2009-01-01

    Endocrinology of the oestrous cycle, pregnancy and early lactation was investigated in captive Western Australian greater bilbies (Macrotis lagotis). Initially, six females were monitored for changes in urogenital cytology, plasma progestogen, pericloacal and pouch morphology in the absence of a male. This was followed by the introduction of a male and a reproductive assessment through mating, gestation and early lactation. In the absence of a male, there was no cyclical pattern of urogenital cytology, pericloacal or pouch development, and progestogen concentrations remained basal. Within 5 days of the introduction of a male, all females had a karyopycnotic index of 100%. Spermatozoa were present in the urogenital smear within 3 days of male introduction in all five females that gave birth. Five to 9 days after the introduction of a male, there was an increase in plasma progestogen concentration that remained elevated for 14-19 days. Six of the seven females gave birth approximately 3 days after reaching peak plasma progestogen concentrations. Gestation length ranged between 14 and 17 days. Plasma progestogen concentrations of the postpartum and early lactation period were lower (P < 0.0001) than during gestation, but greater (P < 0.0001) than those recorded before the introduction of a male. One female that gave birth early in the study that was examined until weaning of the pouch young showed a cyclical pattern of plasma progestogen secretion that ended at weaning. This study provides evidence that the luteal phase in the greater bilby is induced by the presence of a male. Similar to female reproductive physiology in the Peramelidae, elevated progestogen concentration in the greater bilby was extended into lactation.

  19. Slit2/Robo4 Signaling: Potential Role of a VEGF-Antagonist Pathway to Regulate Luteal Permeability

    PubMed Central

    Bekes, I.; Haunerdinger, V.; Sauter, R.; Holzheu, I.; Janni, W.; Wöckel, A.; Wulff, C.

    2017-01-01

    Introduction The corpus luteum (CL) is dependent on luteal vascular permeability, which is controlled by human chorionic gonadotropin (hCG) via vascular endothelial growth factor (VEGF). In this study we investigated the role of a potential VEGF antagonist pathway – Slit2/Robo4 – and its influence on endothelial cell adhesion. Materials and Methods Luteinized granulosa cells (LGCs) were stimulated with hCG in the absence or presence of a VEGF inhibitor. The expression of VEGF and Slit2 were measured. Human umbilical vein endothelial cells (HUVECs) were stimulated with Slit2 or VEGF, and gene expressions of cadherin 5 (CDH5) and claudin 5 (CLDN5) were measured. Following Robo4 knockdown, CDH5, CLDN5 and endothelial permeability were measured. Results Stimulation of human LGCs with hCG significantly increased VEGF while Slit2 expression was significantly suppressed. Inhibition of VEGF action after hCG stimulation did not change Slit2 suppression. Slit2 knockdown did not affect VEGF expression. While VEGF stimulation of HUVECs significantly suppressed CDH5 and CLDN5 gene expression, stimulation of HUVECs with Slit2 resulted in a significant increase in CDH5 and CLDN5. Robo4 knockdown was done, leading to downregulation of CDH5 and CLDN5 which resulted in significantly increased permeability. Conclusions Our results indicate the existence of a VEGF-antagonist pathway in the CL that decreases vascular permeability. During the functional life of the CL the pathway is suppressed by hCG. It is possible that stimulation of this pathway could be used to treat ovarian hyperstimulation syndrome. PMID:28190892

  20. Dydrogesterone vs progesterone for luteal-phase support: systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Barbosa, M W P; Silva, L R; Navarro, P A; Ferriani, R A; Nastri, C O; Martins, W P

    2016-08-01

    To compare the effects of dydrogesterone and progesterone for luteal-phase support (LPS) in women undergoing assisted reproductive techniques (ART). We performed a systematic review to identify relevant randomized controlled trials (RCTs) by searching the following electronic databases: Cochrane CENTRAL, PubMed, Scopus, Web of Science, ClinicalTrials.gov, ISRCTN Registry and WHO ICTRP. The last search was performed in October 2015. Eight RCTs were considered eligible and were included in the review and meta-analyses. There was no relevant difference between oral dydrogesterone and vaginal progesterone for LPS with respect to rate of ongoing pregnancy (risk ratio (RR), 1.04 (95% CI, 0.92-1.18); I(2) , 0%; seven RCTs, 3134 women), clinical pregnancy (RR, 1.07 (95% CI, 0.93-1.23); I(2) , 34%; eight RCTs, 3809 women) or miscarriage (RR, 0.77 (95% CI, 0.53-1.10); I(2) , 0%; seven RCTs, 906 clinical pregnancies). Two of the three studies reporting on dissatisfaction of treatment identified lower levels of dissatisfaction among women using oral dydrogesterone than among women using vaginal progesterone (oral dydrogesterone vs vaginal progesterone capsules: 2/79 (2.5%) vs 90/351 (25.6%), respectively; oral dydrogesterone vs vaginal progesterone gel: 19/411 (4.6%) vs 74/411 (18.0%), respectively). The third study showed no difference in dissatisfaction rate (oral dydrogesterone vs vaginal progesterone capsules: 8/96 (8.3%) vs 8/114 (7.0%), respectively). Oral dydrogesterone seems to be as effective as vaginal progesterone for LPS in ART cycles, and appears to be better tolerated . Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  1. Plasma progesterone levels and luteal activity during gestation and prolonged oviductal egg retention in a tropical lizard, Calotes versicolor.

    PubMed

    Shanbhag, B A; Radder, R S; Saidapur, S K

    2001-07-01

    Plasma progesterone (P) levels and luteal and adrenal activities were studied during normal gestation and unusual prolonged period of oviductal egg retention in a polyautochronic, multiclutched lizard, Calotes versicolor. The normal gestation period (approximately 15 days) was categorized into four stages: stage I--a few hours following ovulation, stage II--eggs with shell and embryo at primitive streak, stage III--embryonic stages 16-20, and stage IV--prior to ovipostion (stages 26-27). The gravid lizards maintained in captivity retained eggs in their oviducts for 45 days. Plasma P levels were low in stage I, increased significantly during stage II, declined in stage III, and reached their lowest in stage IV of gestation. 3Beta-hydroxysteroid dehydrogenase (3beta-HSDH) activity was greater in lutein cells at stage II and was present in traces in stage IV gestation. Interestingly, plasma P titers that were high in lizards with eggs retained longer though the corpora lutea (CL) showed a trace 3beta-HSDH activity. However, 3beta-HSDH activity was greater in the adrenocortical cells in these lizards than that in lizards during a normal gestation period. The present study on C. versicolor shows that the CL remains active and secretes P only during the early part of the gestation. The drop in P level during the later part of gestation might facilitate growth of a second set of vitellogenic follicles. During unfavorable conditions when the lizards are forced to retain eggs in the oviduct, the adrenal glands seem to secrete progesterone to help in egg retention and in inhibition of oviposition.

  2. Oral Progestin Priming Increases Ovarian Sensitivity to Gonadotropin Stimulation and Improves Luteal Function in the Cat1

    PubMed Central

    Stewart, Rosemary A.; Pelican, Katharine M.; Crosier, Adrienne E.; Pukazhenthi, Budhan S.; Wildt, David E.; Ottinger, Mary Ann; Howard, JoGayle

    2012-01-01

    ABSTRACT As the only domesticated species known to exhibit both induced and spontaneous ovulation, the cat is a model for understanding the nuances of ovarian control. To explore ovarian sensitivity to exogenous gonadotropins and the influence of progestin priming, we conducted a study of queens that were down-regulated with oral progestin or allowed to cycle normally, followed by low or high doses of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Our metrics included 1) fecal steroid metabolite profiles before and after ovulation induction, 2) laparoscopic examination of ovarian follicles and corpora lutea (CL) on Days 2 and 17 (Day 0 = hCG administration), and 3) ovariohysterectomy (Day 17) to assess CL progesterone concentrations, morphometrics, and histology. Reproductive tracts from time-matched, naturally mated queens (n = 6) served as controls. Every progestin-primed cat (n = 12) produced the desired response of morphologically similar, fresh CL (regardless of eCG/hCG dose) by Day 2, whereas 41.7% of unprimed counterparts (n = 12) failed to ovulate or had variable-aged CL suggestive of prior spontaneous ovulation (P < 0.05). The ovarian response to low, but not high, eCG/hCG was improved (P < 0.05) in primed compared to unprimed cats, indicating increased sensitivity to gonadotropin in the progestin-primed ovary. Progestin priming prevented hyperelevated fecal steroid metabolites and normalized CL progesterone capacity, but only when combined with low eCG/hCG. However, priming failed to prevent ancillary CL formation, smaller CL mass, or abnormal luteal cell density, which were common to all eCG/hCG-treated cats. Thus, the domestic cat exposed to eCG/hCG produces CL with structural and functional aberrations. These anomalies can be partially mitigated by progestin priming, possibly due to a protective effect of progestin associated with enhanced ovarian sensitivity to gonadotropins. PMID:23100619

  3. Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus sphinx during delayed embryonic development.

    PubMed

    Anuradha; Krishna, Amitabh

    2017-04-12

    The aim of this study was to evaluate the role of prolactin as a modulator of luteal steroidogenesis during the period of delayed embryonic development in Cynopterus sphinx. A marked decline in circulating prolactin levels was noted during the months of November through December coinciding with the period of decreased serum progesterone and delayed embryonic development. The seasonal changes in serum prolactin levels correlated positively with circulating progesterone (P) level, but inversely with circulating melatonin level during first pregnancy showing delayed development in Cynopterus sphinx. The results also showed decreased expression of prolactin receptor-short form (PRL-RS) both in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. Bats treated in vivo with prolactin during the period of delayed development showed significant increase in serum progesterone and estradiol levels together with significant increase in the expression of PRL-RS, luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the ovary. Prolactin stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian progesterone production and the expression of prolactin-receptor, LH-R, STAR and 3β-HSD proteins were noted following the exposure of LH or prolactin in vitro during the delayed period. In conclusion, short-day associated increased melatonin level may be responsible for decreased prolactin release during November-December. The decline in prolactin level might play a role in suppressing P and estradiol-17β (E2) estradiol levels thereby causing delayed embryonic development in C. sphinx.

  4. Quantile regression for climate data

    NASA Astrophysics Data System (ADS)

    Marasinghe, Dilhani Shalika

    Quantile regression is a developing statistical tool which is used to explain the relationship between response and predictor variables. This thesis describes two examples of climatology using quantile regression.Our main goal is to estimate derivatives of a conditional mean and/or conditional quantile function. We introduce a method to handle autocorrelation in the framework of quantile regression and used it with the temperature data. Also we explain some properties of the tornado data which is non-normally distributed. Even though quantile regression provides a more comprehensive view, when talking about residuals with the normality and the constant variance assumption, we would prefer least square regression for our temperature analysis. When dealing with the non-normality and non constant variance assumption, quantile regression is a better candidate for the estimation of the derivative.

  5. Linear regression in astronomy. II

    NASA Technical Reports Server (NTRS)

    Feigelson, Eric D.; Babu, Gutti J.

    1992-01-01

    A wide variety of least-squares linear regression procedures used in observational astronomy, particularly investigations of the cosmic distance scale, are presented and discussed. The classes of linear models considered are (1) unweighted regression lines, with bootstrap and jackknife resampling; (2) regression solutions when measurement error, in one or both variables, dominates the scatter; (3) methods to apply a calibration line to new data; (4) truncated regression models, which apply to flux-limited data sets; and (5) censored regression models, which apply when nondetections are present. For the calibration problem we develop two new procedures: a formula for the intercept offset between two parallel data sets, which propagates slope errors from one regression to the other; and a generalization of the Working-Hotelling confidence bands to nonstandard least-squares lines. They can provide improved error analysis for Faber-Jackson, Tully-Fisher, and similar cosmic distance scale relations.

  6. Luteal 3beta-hydroxysteroid dehydrogenase and 20alpha-hydroxysteroid dehydrogenase activities in the rat corpus luteum of pseudopregnancy: Effect of the deciduoma reaction

    PubMed Central

    Clementi, Marisa A; Deis, Ricardo P; Telleria, Carlos M

    2004-01-01

    Background In the rat, the maintenance of gestation is dependent on progesterone production from the corpora lutea (CL), which are under the control of pituitary, decidual and placental hormones. The luteal metabolism of progesterone during gestation has been amply studied. However, the regulation of progesterone synthesis and degradation during pseudopregnancy (PSP), in which the CL are mainly under the control of pituitary prolactin (PRL), is not well known. The objectives of this investigation were: i) to study the luteal metabolism of progesterone during PSP by measuring the activities of the enzymes 3beta-hydroxysteroid dehydrogenase (3betaHSD), involved in progesterone biosynthesis, and that of 20alpha-hydroxysteroid dehydrogenase (20alphaHSD), involved in progesterone catabolism; and ii) to determine the role of decidualization on progesterone metabolism in PSP. Methods PSP was induced mechanically at 10:00 h on the estrus of 4-day cycling Wistar rats, and the stimulus for decidualization was provided by scratching the uterus on day 4 of PSP. 3betaHSD and 20alphaHSD activities were measured in the CL isolated from ovaries of PSP rats using a spectrophotometric method. Serum concentrations of progesterone, PRL, androstenedione, and estradiol were measured by radioimmunoassay (RIA). Results The PSP stage induced mechanically in cycling rats lasted 11.3 ± 0.09 days (n = 14). Serum progesterone concentration was high until day 10 of PSP, and declined thereafter. Serum PRL concentration was high on the first days of PSP but decreased significantly from days 6 to 9, having minimal values on days 10 and 11. Luteal 3betaHSD activities were elevated until day 6 of PSP, after which they progressively declined, reaching minimal values at the end of PSP. Luteal 20alphaHSD activities were very low until day 9, but abruptly increased at the end of PSP. When the deciduoma was induced by scratching the uterus of pseudopregnant animals on day 4 (PSP+D), PSP was extended to

  7. Luteal 3beta-hydroxysteroid dehydrogenase and 20alpha-hydroxysteroid dehydrogenase activities in the rat corpus luteum of pseudopregnancy: effect of the deciduoma reaction.

    PubMed

    Clementi, Marisa A; Deis, Ricardo P; Telleria, Carlos M

    2004-05-12

    In the rat, the maintenance of gestation is dependent on progesterone production from the corpora lutea (CL), which are under the control of pituitary, decidual and placental hormones. The luteal metabolism of progesterone during gestation has been amply studied. However, the regulation of progesterone synthesis and degradation during pseudopregnancy (PSP), in which the CL are mainly under the control of pituitary prolactin (PRL), is not well known. The objectives of this investigation were: i) to study the luteal metabolism of progesterone during PSP by measuring the activities of the enzymes 3beta-hydroxysteroid dehydrogenase (3betaHSD), involved in progesterone biosynthesis, and that of 20alpha-hydroxysteroid dehydrogenase (20alphaHSD), involved in progesterone catabolism; and ii) to determine the role of decidualization on progesterone metabolism in PSP. PSP was induced mechanically at 10:00 h on the estrus of 4-day cycling Wistar rats, and the stimulus for decidualization was provided by scratching the uterus on day 4 of PSP. 3betaHSD and 20alphaHSD activities were measured in the CL isolated from ovaries of PSP rats using a spectrophotometric method. Serum concentrations of progesterone, PRL, androstenedione, and estradiol were measured by radioimmunoassay (RIA). The PSP stage induced mechanically in cycling rats lasted 11.3 +/- 0.09 days (n = 14). Serum progesterone concentration was high until day 10 of PSP, and declined thereafter. Serum PRL concentration was high on the first days of PSP but decreased significantly from days 6 to 9, having minimal values on days 10 and 11. Luteal 3betaHSD activities were elevated until day 6 of PSP, after which they progressively declined, reaching minimal values at the end of PSP. Luteal 20alphaHSD activities were very low until day 9, but abruptly increased at the end of PSP. When the deciduoma was induced by scratching the uterus of pseudopregnant animals on day 4 (PSP+D), PSP was extended to 18 +/- 2.2 days (n = 8

  8. Evaluating Differential Effects Using Regression Interactions and Regression Mixture Models

    ERIC Educational Resources Information Center

    Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This article focuses on understanding regression mixture models, which are relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their…

  9. Evaluating Differential Effects Using Regression Interactions and Regression Mixture Models

    ERIC Educational Resources Information Center

    Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This article focuses on understanding regression mixture models, which are relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their…

  10. Error bounds in cascading regressions

    USGS Publications Warehouse

    Karlinger, M.R.; Troutman, B.M.

    1985-01-01

    Cascading regressions is a technique for predicting a value of a dependent variable when no paired measurements exist to perform a standard regression analysis. Biases in coefficients of a cascaded-regression line as well as error variance of points about the line are functions of the correlation coefficient between dependent and independent variables. Although this correlation cannot be computed because of the lack of paired data, bounds can be placed on errors through the required properties of the correlation coefficient. The potential meansquared error of a cascaded-regression prediction can be large, as illustrated through an example using geomorphologic data. ?? 1985 Plenum Publishing Corporation.

  11. Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle.

    PubMed

    Navarrete, Maria Alicia H; Maier, Carolina M; Falzoni, Roberto; Quadros, Luiz Gerk de Azevedo; Lima, Geraldo R; Baracat, Edmund C; Nazário, Afonso C P

    2005-01-01

    During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. In mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index (AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period. Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative (n = 21) and luteal (n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy. The proliferation index (PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). The AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. The average AI values in both phases of the menstrual cycle were not statistically significant (P = 0.21). However, the cell renewal index (CRI = PI/AI) was significantly higher in the luteal phase (P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day. We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors.

  12. Impact of luteal phase support with vaginal progesterone on the clinical pregnancy rate in intrauterine insemination cycles stimulated with gonadotropins: a randomized multicenter study.

    PubMed

    Peeraer, Karen; D'Hooghe, Thomas; Laurent, Pascale; Pelckmans, Sofie; Delvigne, Annick; Laenen, Annouschka; Welkenhuysen, Myriam; Wyns, Christine; De Neubourg, Diane

    2016-11-01

    To evaluate the effect of luteal phase support (LPS) in intrauterine insemination (IUI) cycles stimulated with gonadotropins. Randomized multicenter trial. Academic tertiary care centers and affiliated secondary care centers. Three hundred and ninety-three normo-ovulatory patients, <43 years, with body mass index ≤30 kg/m(2), in their first IUI cycle, with at least one patent tube, a normal uterine cavity, and a male partner with total motile sperm count ≥5 million after capacitation. Gonadotropin stimulation, IUI, randomization to LPS using vaginal progesterone gel (n = 202) or no LPS (n = 191). Clinical pregnancy rate, live-birth rate, miscarriage rate, and duration of the luteal phase. The primary outcome, the clinical pregnancy rate, was not statistically different between the treatment group (16.8%) and the control group (11%) (relative risk [RR] 1.54; 95% confidence interval [CI], 0.89-2.67). Similarly, the secondary outcome, the live-birth rate, was 14.9% in the treatment group and 9.4% in the control group (RR 1.60; 95% CI, 0.89-2.87). The mean duration of the luteal phase was about 2 days longer in the treatment group (16.6 ± 2.2 days) compared with the control group (14.6 ± 2.5 days) (mean difference 2.07; 95% CI, 1.58-2.56). Although a trend toward a higher clinical pregnancy rate as well as live-birth rate was observed in the treatment group, the difference with the control group was not statistically significant. NCT01826747. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Effects of different five-day progesterone-based synchronization protocols on the estrous response and follicular/luteal dynamics in dairy cows

    PubMed Central

    LÓPEZ-GATIUS, Fernando; LÓPEZ-HELGUERA, Irene; DE RENSIS, Fabio; GARCIA-ISPIERTO, Irina

    2015-01-01

    This study compared the responses shown by lactating dairy cows to four different P4-based protocols for AI at estrus. Cows with no estrous signs 96 h after progesterone intravaginal device (PRID) removal were subjected to fixed-time AI (FTAI), and their data were also included in the study. In Experiment I, follicular/luteal and endometrial dynamics were assessed every 12 h from the beginning of treatment until AI. The estrous response was examined in Experiment II, and fertility was assessed in both experiments. The protocols consisted of a PRID fitted for five days, along with the administration of different combinations of gonadotropin releasing hormone (GnRH), equine chorionic gonadotropin and a single or double dose (24 h apart) of prostaglandin F2α. In Experiment I (40 cows), animals receiving GnRH at the start of treatment showed a significantly higher ovulation rate during the PRID insertion period while estrus was delayed. In Experiment II (351 cows), according to the odds ratios, cows showing luteal activity at the time of treatment were less likely to show estrus than cows with no signs of luteal activity. Treatment affected the estrous response and the interval from PRID removal to estrus but did not affect conception rates 28–34 days post AI. Primiparous cows displayed a better estrous response than multiparous cows. Our findings reveal acceptable results of 5-day P4-based protocols for AI at estrus in high-producing dairy cows. Time from treatment to estrus emerged as a good guide for FTAI after a 5-day P4-based synchronization protocol. PMID:26211922

  14. Progesterone for Luteal Phase Support in In Vitro Fertilization: Comparison of Vaginal and Rectal Pessaries to Vaginal Capsules: A Randomized Controlled Study

    PubMed Central

    Khrouf, Mohamed; Slimani, Soufiene; Khrouf, Myriam Razgallah; Braham, Marouen; Bouyahia, Maha; Berjeb, Khadija Kacem; Chaabane, Hanene Elloumi; Merdassi, Ghaya; Kaffel, Aida Zahaf; Zhioua, Amel; Zhioua, Fethi

    2016-01-01

    BACKGROUND In IVF, Luteal phase support is usually performed using vaginal progesterone. A part of patients using this route reports being uncomfortable with this route. We tried to study whether the rectal route could be an effective alternative and associated with less discomfort. PATIENTS AND METHODS A prospective randomized controlled study. All patient were eligible for IVF treatment for infertility. After oocyte pickup, 186 patients were allocated to one the following protocols for luteal phase support: (i) rectal pessaries group: natural progesterone pessaries administered rectally 200 mg three times a day, (ii) vaginal pessaries group: natural progesterone pessaries administered vaginally 200 mg three times a day), and (iii) vaginal capsules group: natural micronized progesterone capsules administered vaginally 200 mg three times a day. On the day of pregnancy test, patients were asked to fill in a questionnaire conducted by an investigator in order to assess the tolerability and side effects of the LPS treatment taken. The primary endpoint was the occurrence of perineal irritation. RESULTS Fifty eight patients were assigned to the rectal pessaries group, 68 patients to the vaginal pessaries group, and 60 patients to the vaginal capsules group. All patients adhered to their allocated treatment. Implantation and clinical pregnancy rates per transfer did not differ between the three groups. Perineal irritation, which was our primary endpoint, was the same for all the three groups (respectively 1.7 % versus 5.9 % versus 11.7%). Regarding the other side effects, more patients experienced constipation and flatulence with the rectal route, whereas more patients reported vaginal discharge in the vaginal capsules group. CONCLUSION Rectal administration for luteal phase support is effective and well accepted alternative to vaginal route. PMID:28096703

  15. Embryo implantation during the short luteal phase of the corn mouse, Calomys musculinus, and the apparent lack of a lactational diapause in South American murid rodents.

    PubMed

    Buzzio, O L; Koninckx, A; Carreno, N B; Castro-Vazquez, A

    2001-05-01

    As the corn mouse, Calomys musculinus, has a short luteal phase (2-3 days) that is not prolonged after copulation, it was hypothesized that (i) implantation would occur at the end of this phase, that is, earlier than it occurs in most murid species that have been studied, and (ii) a lactational embryonic diapause would not occur during the luteal phase. These hypotheses were tested in females that had copulated during postpartum oestrus and were either lactating or not lactating. Data were recorded from day 3 to day 5 of pregnancy (day 1 = day after coitus), at both 03:00-05:00 h and 17:00-19:00 h. Evidence of implantation in both non-lactating and lactating animals was apparent at 03:00-05:00 h on day 4 (endometrial 'blue reaction' in all cases and failure to recover free uterine embryos in some cases) and implantation swellings appeared within 24 h in both groups. In another experiment, the increase in duration of interbirth intervals in continuously mated females and their correlation with the number of suckling young were compared among C. musculinus, C. laucha, Akodon molinae (South American murid species) and Peromyscus maniculatus (a North American murid in which a lactational embryonic diapause has been shown). The results were indicative of a lactational embryonic diapause in the North American species, but not in the South American species. It was concluded that in C. musculinus (i) implantation occurs at the end of the spontaneous luteal phase, and (ii) that a lactational embryonic diapause does not occur: the absence of a lactational embryonic diapause may be common to other South American murid rodents.

  16. Expression of calbindin-D9k and vitamin D receptor in the uterus of Egyptian buffalo during follicular and luteal phases.

    PubMed

    Emam, Mahmoud Abdelghaffar; Abouelroos, Mahmoud E A; Gad, Fatma A

    2016-06-01

    Uteri of mature Egyptian buffalo cows (5-10 years old) were collected at follicular (n=12) and luteal (n=16) phases of estrous cycle to investigate the expression of calbindin-D9k (CaPB-9k) and vitamin D receptor (VDR). This study was done using avidin-biotin immunohistochemistry method. In addition, blood levels of calcium (Ca), vitamin D3 (Vit D), estrogen (E2) and progesterone (P4) were measured. The immunohistochemical findings restricted the expressions of CaBP-9k and VDR to the luminal and glandular epithelia of the endometrium implicating the importance of CaBP-9K and VDR in the function of endometrial epithelium, especially the glandular one, in order to prepare a receptive uterus. On the other hand, the myometrium did not express CaBP-9k or VDR that denies the potential role of CaBP-9k and VDR in the uterine contractility during the estrous cycle of Egyptian buffalo. All of Ca, Vit D, and P4 blood levels significantly (P<0.05) increased during luteal phase however, blood level of E2 significantly (P<0.05) increased during follicular phase. The expressions of CaBP-9k and VDR in the uterus of Egyptian buffalo were significantly (P<0.05) higher during luteal (P4 dominant) phase than during the follicular (E2 dominant) phase indicating that P4 up-regulates the expressions of CaBP-9k and VDR. In view of these observations, this study represents the first characterization of CaBP-9K and VDR expression in the uterus of Egyptian buffalo and suggests the pivotal role of CaBP-9k and VDR in the uterine receptivity. Furthermore, it demonstrates the regulatory role of P4 for expressions of CaBP-9k and VDR in buffalo uterus. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Impact of Buserelin Acetate or hCG Administration on the Day of First Artificial Insemination on Subsequent Luteal Profile and Conception Rate in Murrah Buffalo (Bubalus bubalis).

    PubMed

    Pandey, A K; Ghuman, Sps; Dhaliwal, G S; Agarwal, S K; Phogat, J B

    2016-08-01

    This study was designed to investigate the impact of buserelin acetate (BA) or human chorionic gonadotropin (hCG) administration on the day of first artificial insemination (AI) on subsequent luteal profile (diameter of corpus luteum (CL) and plasma progesterone) and conception rate in Murrah buffalo. The present experiment was carried out at two locations in 117 buffalo that were oestrus-synchronized using cloprostenol (500 μg) administered (i.m.) 11 days apart followed by AI during standing oestrus. Based on treatment (i.m.) at the time of AI, buffalo were randomly categorized (n = 39 in each group) into control (isotonic saline solution, 5 ml), dAI-BA (buserelin acetate, 20 μg) and dAI-hCG (hCG, 3000 IU) group. Out of these, 14 buffalo of each group were subjected to ovarian ultrasonography on the day of oestrus to monitor the preovulatory follicle and on days 5, 12, 16 and 21 post-ovulation to monitor CL diameter. On the day of each sonography, jugular vein blood samples were collected for the estimation of progesterone concentrations. All the buffalo (n = 117) were confirmed for pregnancy on day 40 post-ovulation. The conception rate was better (p < 0.05) in dAI-BA (51.3%) and dAI-hCG (66.7%) groups as compared to their control counterparts (30.8%). Furthermore, the buffalo of dAI-hCG group had improved (p < 0.05) luteal profile, whereas the buffalo of dAI-BA group failed (p > 0.05) to exhibit stimulatory impact of treatment on luteal profile when compared to control group. In brief, buserelin acetate or hCG treatment on the day of first AI leads to an increase in conception rate; however, an appreciable impact on post-ovulation luteal profile was observed only in hCG-treated Murrah buffalo. © 2016 Blackwell Verlag GmbH.

  18. Antinidatory effect of luteal phase administration of mifepristone (RU486) is associated with changes in endometrial prostaglandins during the implantation window.

    PubMed

    Nayak, N R; Sengupta, J; Ghosh, D

    1998-08-01

    Luteal phase administration of mifepristone provides a significant degree of pregnancy protection to monkeys and women. Among several proposed mediators of the antinidatory action of luteal phase mifepristone, prostaglandins (PG) at the endometrial level appear important, and was examined in the present study using the rhesus monkey as the primate model. To this end, the concentrations of PGE2 and PGF2 alpha in endometrium and the profiles of cyclooxygenase (COX) and 15-hydroxy prostaglandin dehydrogenase (PGDH) were examined in untreated control animals, in animals subjected to mifepristone treatment (2 mg/day) alone or along with diclofenac (25 mg/day), or along with a PGE1 analog (100 micrograms misoprostol), in animals subjected to diclofenac alone treatment, and in animals treated with misoprostol alone on cycle days 16, 17, and 18. Tissue samples were collected on day 20 of treatment cycles from animals with discernible corpora lutea. Early luteal phase treatment with diclofenac did not result in any remarkable change in endometrial prostaglandin concentrations, however, there was an increase in the profile of COX. Animals exposed to misoprostol in the prereceptive stage, on the other hand, exhibited decreased expression of endometrial COX. The concentrations of PGF2 alpha and PGE2, as well as the ratios of PGF2 alpha to PGE2 concentrations, were increased along with a decrease in COX and PGD in endometrial samples following luteal phase mifepristone treatment. Although the underlying cellular mechanism of regulation of COX and PGDH in mifepistone-treated endometrium remains to be examined, the decrease in PG catabolism through low PGDH may contribute to the increased PG and high ratio of PGF2 alpha to PGE2 in mifepristone-exposed endometrium. It is plausible that mifepristone action on endometrial cells is mediated by an altered ratio of PGF2 alpha to PGE2. Furthermore, it appears that the regulation of PG milieu by COX and PGDH activities in reproductive

  19. Precision Efficacy Analysis for Regression.

    ERIC Educational Resources Information Center

    Brooks, Gordon P.

    When multiple linear regression is used to develop a prediction model, sample size must be large enough to ensure stable coefficients. If the derivation sample size is inadequate, the model may not predict well for future subjects. The precision efficacy analysis for regression (PEAR) method uses a cross- validity approach to select sample sizes…

  20. Logistic Regression: Concept and Application

    ERIC Educational Resources Information Center

    Cokluk, Omay

    2010-01-01

    The main focus of logistic regression analysis is classification of individuals in different groups. The aim of the present study is to explain basic concepts and processes of binary logistic regression analysis intended to determine the combination of independent variables which best explain the membership in certain groups called dichotomous…

  1. Fungible weights in logistic regression.

    PubMed

    Jones, Jeff A; Waller, Niels G

    2016-06-01

    In this article we develop methods for assessing parameter sensitivity in logistic regression models. To set the stage for this work, we first review Waller's (2008) equations for computing fungible weights in linear regression. Next, we describe 2 methods for computing fungible weights in logistic regression. To demonstrate the utility of these methods, we compute fungible logistic regression weights using data from the Centers for Disease Control and Prevention's (2010) Youth Risk Behavior Surveillance Survey, and we illustrate how these alternate weights can be used to evaluate parameter sensitivity. To make our work accessible to the research community, we provide R code (R Core Team, 2015) that will generate both kinds of fungible logistic regression weights. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  2. Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes.

    PubMed

    Qin, B; Dawson, H; Polansky, M M; Anderson, R A

    2009-07-01

    We have previously reported that the obesity-associated proinflammatory cytokine, TNF-alpha, stimulates the overproduction of intestinal apolipoprotein (apo) B48 containing lipoproteins. In the current study, we have evaluated whether a water-soluble cinnamon extract [CE (Cinnulin PF)] attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339 treated hamsters, and whether CE inhibits the oversecrection of apoB48-induced by TNF-alpha in enterocytes in a 35S labeling study. In vivo, oral treatment of Cinnulin PF (50 mg per kg BW), inhibited the postprandial overproduction of apoB48-containing lipoproteins and serum triglyceride levels. In ex vivo 35S labeling studies, CE (10 and 20 microg/ml) inhibited the oversecretion of apoB48 induced by TNF-alpha treated enterocytes into the media. To determine the molecular mechanisms, TNF-alpha treated primary enterocytes isolated from chow-fed hamsters, were incubated with CE (10 microg/ml), and the expression of the inflammatory factor genes, IL1-beta, IL-6, and TNF-alpha, insulin signaling pathway genes, insulin receptor (IR), IRS1, IRS2, phosphatidylinositol 3-kinase (PI3-K), Akt1 and phosphatase and tensin homology (PTEN), as well as the key regulators of lipid metabolism, cluster of differentiation (CD)36, microsomal triglyceride transfer protein (MTTP), and sterol regulatory element binding protein (SREBP)-1c were evaluated. Quantitative real-time PCR assays showed that CE treatment decreased the mRNA expression of IL-1beta, IL-6 and TNF-alpha, improved the mRNA expression of IR, IRS1, IRS2, PI3K and Akt1, inhibited CD36, MTTP, and PTEN, and enhanced the impaired SREBP-1c expression in TNF-alpha treated enterocytes. These data suggest that a water extract of cinnamon reverses TNF-alpha-induced overproduction of intestinal apoB48 by regulating gene expression involving inflammatory, insulin, and lipoprotein signaling pathways. In conclusion, Cinulin PF improves inflammation related intestinal dyslipidemia.

  3. A P2X ion channel-triggered NF-kappaB pathway enhances TNF-alpha-induced IL-8 expression in airway epithelial cells.

    PubMed

    Théâtre, Emilie; Bours, Vincent; Oury, Cécile

    2009-12-01

    Extracellular ATP, acting at P2Y and P2X receptors, has recently been shown to contribute to airway inflammation. The aim of our study was to investigate the molecular mechanisms involved in the ATP-dependent regulation of IL-8 production by airway epithelial cells. Treatment of human normal tracheal (NT)-1 cells with ATP or its two analogs, alpha,beta-methylene ATP (alpha,beta-meATP) and 2'- and 3'-O-(4-benzoyl-benzoyl)-ATP (BzATP) activated NF-kappaB through the IkappaB kinase (IKK) complex, a process requiring Ca(2+), calmodulin (CaM), and Ca(2+)/CaM-dependent kinase (CaMK), but independent from phospholipase C. alpha,beta-meATP-induced IKK activation also occurred in the alveolar A549 cell line. Real-time RT-PCR revealed that NT-1 and A549 cells expressed P2X(4), P2X(5),and P2X(6) subtype mRNAs, whereas P2X(7) mRNAs were only detected in NT-1 cells. Polarized human primary nasal epithelial cells expressed all four P2X subtypes. Both alpha,beta-meATP and BzATP caused Ca(2+)-dependent binding of phosphorylated p65 (S536) NF-kappaB subunit to the endogenous IL-8 gene promoter in NT-1 cells. Although these agonists did not induce significant IL-8 gene expression by these cells, they markedly enhanced TNF-alpha-induced NF-kappaB activation, resulting in increased IL-8 expression and release. Application of alpha,beta-meATP or BzATP at the apical side of polarized human primary nasal epithelial cells sufficed to cause CaMK-dependent IL-8 release by these cells. Thus, ATP promotes TNF-alpha-elicited IL-8 expression through P2X ion channel-triggered Ca(2+) entry, leading to CaMK-dependent IKK activation and binding of active p65 to IL-8 gene promoter.

  4. Interferon-alpha-induced inflammation is associated with reduced glucocorticoid negative feedback sensitivity and depression in patients with hepatitis C virus.

    PubMed

    Felger, Jennifer C; Haroon, Ebrahim; Woolwine, Bobbi J; Raison, Charles L; Miller, Andrew H

    2016-11-01

    Major medical illnesses are associated with increased risk for depression and alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Pathophysiological processes such as inflammation that occur as a part of medical illnesses and their treatments have been shown to cause depressive symptoms, and may also affect the HPA axis. We previously reported that patients with hepatitis C virus chronically administered interferon (IFN)-alpha develop increased evening plasma cortisol concentrations and a flattened diurnal cortisol slope, which correlated with increased tumor necrosis factor (TNF) and its soluble receptor 2 (sTNFR2). Increased TNF and sTNFR2 were further correlated with depression and fatigue scores. The current study examined whether flattened cortisol slope might be secondary to reduced glucocorticoid receptor (GR) sensitivity, by measuring glucocorticoid negative feedback to dexamethasone (DEX) administration followed by corticotropin releasing hormone (CRH) challenge. In an exploratory analysis, 28 male and female patients with hepatitis C virus were studied at baseline (Visit 1) and after 12weeks (Visit 2) of either IFN-alpha plus ribavirin (n=17) or no treatment (n=11). Patients underwent dexamethasone DEX-CRH challenge, neuropsychiatric assessments, and measurement of plasma TNF and sTNFR2 during each visit. IFN-alpha did not affect neuroendocrine responses following CRH but did increase post-DEX cortisol, which was correlated with flattening of the diurnal cortisol slope (r=0.57, p=0.002) and with increased depression scores (r=0.38, p=0.047). Furthermore, the change in post-DEX cortisol was associated with IFN-alpha-induced increase in sTNFR2 (r=0.51, p=006), which was in turn correlated with depression (r=0.63, p<0.001) and fatigue (r=0.51, p=0.005) scores. Whereas the relationship between sTNFR2 and depression scores were independent of the change in post-DEX cortisol, the correlation between post-DEX cortisol and depression scores was not

  5. Rank regression: an alternative regression approach for data with outliers.

    PubMed

    Chen, Tian; Tang, Wan; Lu, Ying; Tu, Xin

    2014-10-01

    Linear regression models are widely used in mental health and related health services research. However, the classic linear regression analysis assumes that the data are normally distributed, an assumption that is not met by the data obtained in many studies. One method of dealing with this problem is to use semi-parametric models, which do not require that the data be normally distributed. But semi-parametric models are quite sensitive to outlying observations, so the generated estimates are unreliable when study data includes outliers. In this situation, some researchers trim the extreme values prior to conducting the analysis, but the ad-hoc rules used for data trimming are based on subjective criteria so different methods of adjustment can yield different results. Rank regression provides a more objective approach to dealing with non-normal data that includes outliers. This paper uses simulated and real data to illustrate this useful regression approach for dealing with outliers and compares it to the results generated using classical regression models and semi-parametric regression models.

  6. Expression of macrophage migration inhibitory factor (MIF) in bovine oviducts is higher in the postovulatory phase than during the oestrus and luteal phase.

    PubMed

    Nahar, Asrafun; Kadokawa, Hiroya

    2016-07-28

    Whether macrophage migration inhibitory factor (MIF) in the bovine oviduct is important for early embryogenesis has not been well substantiated. The aim of the present study was to test the hypothesis that bovine oviduct expresses higher levels of MIF during the post-ovulation phase. Both ampullary and isthmic samples were collected from Japanese black heifers during oestrus (Day 0; n=5), postovulation (Day 3; n=6) and luteal phase (Days 9-12; n=5). MIF mRNA and protein were extracted from the ampullary and isthmic samples and their levels measured by real-time polymerase chain reaction and western blot analysis respectively. Fluorescent immunohistochemistry was performed on frozen ampullary and isthmic sections using antibodies against MIF. MIF mRNA and protein expression was higher in the postovulatory phase than during oestrus and the luteal phase (P<0.05). Fluorescent immunohistochemistry confirmed that in all phases of the oestrous cycle evaluated, the primary site of MIF expression in the ampulla and isthmus was the tunica mucosa. In conclusion, the bovine ampulla and isthmus have higher MIF expression during the postovulatory phase. Further studies are needed to clarify the role of MIF in bovine oviducts.

  7. Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

    PubMed

    Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

    2016-10-01

    For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

  8. Luteal-long GnRH agonist versus flexible-multidose GnRH antagonist protocols for overweight and obese patients who underwent ICSI.

    PubMed

    Esinler, I; Bozdag, G; Esinler, D; Lale, K S; Yarali, H

    2015-04-01

    A total of 413 consecutive infertile patients (572 cycles) with a body mass index (BMI) of ≥ 25 kg/m(2) were enrolled into the study. The luteal-long GnRH agonist group (Group I) constituted 211 patients (300 cycles) and the flexible-multidose GnRH antagonist group (Group II) constituted 202 patients (272 cycles). The duration of stimulation (d) (10.1 ± 2.5 vs. 9.2 ± 2.0; p < 0.01); the total dose of gonadotrophin used (IU) (3,099.4 ± 2,885.0 vs. 2,684.0 ± 1,046.4; p < 0.05) and the E2 level on the day of hCG (pg/ml) (2,375.8 ± 1,554.6 vs. 1,905.6 ± 1,598.8; p < 0.01) were significantly lower in Group II when compared with Group I. However, the ongoing pregnancy per embryo transfer (37.0% vs. 25.7%; p < 0.05) and the implantation rate (25.7% vs. 15.6%; p < 0.01) were significantly lower in Group II when compared with Group I. In conclusion, we noted that the luteal-long GnRH agonist protocol produced higher implantation rates and higher clinical-ongoing pregnancy rates in overweight and obese patients when compared with the flexible-multidose GnRH antagonist protocol.

  9. High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques.

    PubMed

    Vishwanathan, Sundaram A; Guenthner, Patricia C; Lin, Carol Y; Dobard, Charles; Sharma, Sunita; Adams, Debra R; Otten, Ron A; Heneine, Walid; Hendry, R Michael; McNicholl, Janet M; Kersh, Ellen N

    2011-08-01

    Fluctuations in susceptibility to HIV or SHIV during the menstrual cycle are currently not fully documented. To address this, the time point of infection was determined in 19 adult female pigtail macaques vaginally challenged during their undisturbed menstrual cycles with repeated, low-dose SHIV(SF162P3) exposures. Eighteen macaques (95%) first displayed viremia in the follicular phase, as compared with 1 macaque (5%) in the luteal phase (P < 0.0001). Due to a viral eclipse phase, we estimated a window of most frequent virus transmission between days 24 and 31 of the menstrual cycle, in the late luteal phase. Thus, susceptibility to vaginal SHIV infection is significantly elevated in the second half of the menstrual cycle when progesterone levels are high and when local immunity may be low. Such susceptibility windows have been postulated before but not definitively documented. Our data support the findings of higher susceptibility to HIV in women during progesterone-dominated periods including pregnancy and contraceptive use.

  10. Practical Session: Simple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    Two exercises are proposed to illustrate the simple linear regression. The first one is based on the famous Galton's data set on heredity. We use the lm R command and get coefficients estimates, standard error of the error, R2, residuals …In the second example, devoted to data related to the vapor tension of mercury, we fit a simple linear regression, predict values, and anticipate on multiple linear regression. This pratical session is an excerpt from practical exercises proposed by A. Dalalyan at EPNC (see Exercises 1 and 2 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_4.pdf).

  11. Splines for diffeomorphic image regression.

    PubMed

    Singh, Nikhil; Niethammer, Marc

    2014-01-01

    This paper develops a method for splines on diffeomorphisms for image regression. In contrast to previously proposed methods to capture image changes over time, such as geodesic regression, the method can capture more complex spatio-temporal deformations. In particular, it is a first step towards capturing periodic motions for example of the heart or the lung. Starting from a variational formulation of splines the proposed approach allows for the use of temporal control points to control spline behavior. This necessitates the development of a shooting formulation for splines. Experimental results are shown for synthetic and real data. The performance of the method is compared to geodesic regression.

  12. Abstract Expression Grammar Symbolic Regression

    NASA Astrophysics Data System (ADS)

    Korns, Michael F.

    This chapter examines the use of Abstract Expression Grammars to perform the entire Symbolic Regression process without the use of Genetic Programming per se. The techniques explored produce a symbolic regression engine which has absolutely no bloat, which allows total user control of the search space and output formulas, which is faster, and more accurate than the engines produced in our previous papers using Genetic Programming. The genome is an all vector structure with four chromosomes plus additional epigenetic and constraint vectors, allowing total user control of the search space and the final output formulas. A combination of specialized compiler techniques, genetic algorithms, particle swarm, aged layered populations, plus discrete and continuous differential evolution are used to produce an improved symbolic regression sytem. Nine base test cases, from the literature, are used to test the improvement in speed and accuracy. The improved results indicate that these techniques move us a big step closer toward future industrial strength symbolic regression systems.

  13. Multiple Regression and Its Discontents

    ERIC Educational Resources Information Center

    Snell, Joel C.; Marsh, Mitchell

    2012-01-01

    Multiple regression is part of a larger statistical strategy originated by Gauss. The authors raise questions about the theory and suggest some changes that would make room for Mandelbrot and Serendipity.

  14. Time-warped geodesic regression.

    PubMed

    Hong, Yi; Singh, Nikhil; Kwitt, Roland; Niethammer, Marc

    2014-01-01

    We consider geodesic regression with parametric time-warps. This allows for example, to capture saturation effects as typically observed during brain development or degeneration. While highly-flexible models to analyze time-varying image and shape data based on generalizations of splines and polynomials have been proposed recently, they come at the cost of substantially more complex inference. Our focus in this paper is therefore to keep the model and its inference as simple as possible while allowing to capture expected biological variation. We demonstrate that by augmenting geodesic regression with parametric time-warp functions, we can achieve comparable flexibility to more complex models while retaining model simplicity. In addition, the time-warp parameters provide useful information of underlying anatomical changes as demonstrated for the analysis of corpora callosa and rat calvariae. We exemplify our strategy for shape regression on the Grassmann manifold, but note that the method is generally applicable for time-warped geodesic regression.

  15. Time-Warped Geodesic Regression

    PubMed Central

    Hong, Yi; Singh, Nikhil; Kwitt, Roland; Niethammer, Marc

    2016-01-01

    We consider geodesic regression with parametric time-warps. This allows, for example, to capture saturation effects as typically observed during brain development or degeneration. While highly-flexible models to analyze time-varying image and shape data based on generalizations of splines and polynomials have been proposed recently, they come at the cost of substantially more complex inference. Our focus in this paper is therefore to keep the model and its inference as simple as possible while allowing to capture expected biological variation. We demonstrate that by augmenting geodesic regression with parametric time-warp functions, we can achieve comparable flexibility to more complex models while retaining model simplicity. In addition, the time-warp parameters provide useful information of underlying anatomical changes as demonstrated for the analysis of corpora callosa and rat calvariae. We exemplify our strategy for shape regression on the Grassmann manifold, but note that the method is generally applicable for time-warped geodesic regression. PMID:25485368

  16. Multiple Regression and Its Discontents

    ERIC Educational Resources Information Center

    Snell, Joel C.; Marsh, Mitchell

    2012-01-01

    Multiple regression is part of a larger statistical strategy originated by Gauss. The authors raise questions about the theory and suggest some changes that would make room for Mandelbrot and Serendipity.

  17. Wrong Signs in Regression Coefficients

    NASA Technical Reports Server (NTRS)

    McGee, Holly

    1999-01-01

    When using parametric cost estimation, it is important to note the possibility of the regression coefficients having the wrong sign. A wrong sign is defined as a sign on the regression coefficient opposite to the researcher's intuition and experience. Some possible causes for the wrong sign discussed in this paper are a small range of x's, leverage points, missing variables, multicollinearity, and computational error. Additionally, techniques for determining the cause of the wrong sign are given.

  18. Wrong Signs in Regression Coefficients

    NASA Technical Reports Server (NTRS)

    McGee, Holly

    1999-01-01

    When using parametric cost estimation, it is important to note the possibility of the regression coefficients having the wrong sign. A wrong sign is defined as a sign on the regression coefficient opposite to the researcher's intuition and experience. Some possible causes for the wrong sign discussed in this paper are a small range of x's, leverage points, missing variables, multicollinearity, and computational error. Additionally, techniques for determining the cause of the wrong sign are given.

  19. XRA image segmentation using regression

    NASA Astrophysics Data System (ADS)

    Jin, Jesse S.

    1996-04-01

    Segmentation is an important step in image analysis. Thresholding is one of the most important approaches. There are several difficulties in segmentation, such as automatic selecting threshold, dealing with intensity distortion and noise removal. We have developed an adaptive segmentation scheme by applying the Central Limit Theorem in regression. A Gaussian regression is used to separate the distribution of background from foreground in a single peak histogram. The separation will help to automatically determine the threshold. A small 3 by 3 widow is applied and the modal of the local histogram is used to overcome noise. Thresholding is based on local weighting, where regression is used again for parameter estimation. A connectivity test is applied to the final results to remove impulse noise. We have applied the algorithm to x-ray angiogram images to extract brain arteries. The algorithm works well for single peak distribution where there is no valley in the histogram. The regression provides a method to apply knowledge in clustering. Extending regression for multiple-level segmentation needs further investigation.

  20. Interpretation of Standardized Regression Coefficients in Multiple Regression.

    ERIC Educational Resources Information Center

    Thayer, Jerome D.

    The extent to which standardized regression coefficients (beta values) can be used to determine the importance of a variable in an equation was explored. The beta value and the part correlation coefficient--also called the semi-partial correlation coefficient and reported in squared form as the incremental "r squared"--were compared for…

  1. Interquantile Shrinkage in Regression Models

    PubMed Central

    Jiang, Liewen; Wang, Huixia Judy; Bondell, Howard D.

    2012-01-01

    Conventional analysis using quantile regression typically focuses on fitting the regression model at different quantiles separately. However, in situations where the quantile coefficients share some common feature, joint modeling of multiple quantiles to accommodate the commonality often leads to more efficient estimation. One example of common features is that a predictor may have a constant effect over one region of quantile levels but varying effects in other regions. To automatically perform estimation and detection of the interquantile commonality, we develop two penalization methods. When the quantile slope coefficients indeed do not change across quantile levels, the proposed methods will shrink the slopes towards constant and thus improve the estimation efficiency. We establish the oracle properties of the two proposed penalization methods. Through numerical investigations, we demonstrate that the proposed methods lead to estimations with competitive or higher efficiency than the standard quantile regression estimation in finite samples. Supplemental materials for the article are available online. PMID:24363546

  2. Survival Data and Regression Models

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-12-01

    We start this chapter by introducing some basic elements for the analysis of censored survival data. Then we focus on right censored data and develop two types of regression models. The first one concerns the so-called accelerated failure time models (AFT), which are parametric models where a function of a parameter depends linearly on the covariables. The second one is a semiparametric model, where the covariables enter in a multiplicative form in the expression of the hazard rate function. The main statistical tool for analysing these regression models is the maximum likelihood methodology and, in spite we recall some essential results about the ML theory, we refer to the chapter "Logistic Regression" for a more detailed presentation.

  3. Regressive evolution in Astyanax cavefish.

    PubMed

    Jeffery, William R

    2009-01-01

    A diverse group of animals, including members of most major phyla, have adapted to life in the perpetual darkness of caves. These animals are united by the convergence of two regressive phenotypes, loss of eyes and pigmentation. The mechanisms of regressive evolution are poorly understood. The teleost Astyanax mexicanus is of special significance in studies of regressive evolution in cave animals. This species includes an ancestral surface dwelling form and many con-specific cave-dwelling forms, some of which have evolved their recessive phenotypes independently. Recent advances in Astyanax development and genetics have provided new information about how eyes and pigment are lost during cavefish evolution; namely, they have revealed some of the molecular and cellular mechanisms involved in trait modification, the number and identity of the underlying genes and mutations, the molecular basis of parallel evolution, and the evolutionary forces driving adaptation to the cave environment.

  4. Associations of Serum Levels of Sex Hormones in Follicular and Luteal Phases of the Menstrual Cycle with Breast Tissue Characteristics in Young Women

    PubMed Central

    Taylor, Monica; Dunn, Sheila; Martin, Lisa; Chavez, Sonia; Stanitz, Greg; Huszti, Ella; Minkin, Salomon; Boyd, Norman

    2016-01-01

    Background In previous work in young women aged 15–30 years we measured breast water and fat using MR and obtained blood for hormone assays on the same day in the follicular phase of the menstrual cycle. Only serum growth hormone levels and sex hormone binding globulin (SHBG) were significantly associated with percent breast water after adjustment for covariates. The sex hormones estradiol, progesterone and testosterone were not associated with percent water in the breast in the follicular phase of the menstrual cycle. In the present study we have examined the association of percent breast water with serum levels of sex hormones in both follicular and luteal phase of the menstrual cycle. Methods In 315 healthy white Caucasian young women aged 15–30 with regular menstrual cycles who had not used oral contraceptives or other hormones in the previous 6 months, we used MR to determine percent breast water, and obtained blood samples for hormone assays within 10 days of the onset of the most recent menstrual cycle (follicular phase) of the cycle on the same day as the MR scan, and a second blood sample on days 19–24 of the cycle. Serum progesterone levels of > = 5 mmol/L in days 19–24 were used to define the 225 subjects with ovulatory menstrual cycles, whose data are the subject of the analyses shown here. Results SHBG was positively associated with percent water in both follicular and luteal phases of the menstrual cycle. Total and free estradiol and total and free testosterone were not associated with percent water in the follicular phase, but in young women with ovulatory cycles, were all negatively associated with percent water in the luteal phase. Conclusions Our results from young women aged 15–30 years add to the evidence that the extent of fibroglandular tissue in the breast that is reflected in both mammographic density and breast water is associated positively with higher serum levels of SHBG, but not with higher levels of sex hormones. PMID

  5. Logistic regression for circular data

    NASA Astrophysics Data System (ADS)

    Al-Daffaie, Kadhem; Khan, Shahjahan

    2017-05-01

    This paper considers the relationship between a binary response and a circular predictor. It develops the logistic regression model by employing the linear-circular regression approach. The maximum likelihood method is used to estimate the parameters. The Newton-Raphson numerical method is used to find the estimated values of the parameters. A data set from weather records of Toowoomba city is analysed by the proposed methods. Moreover, a simulation study is considered. The R software is used for all computations and simulations.

  6. A role for the Rho-p160 Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1alpha-induced lymphocyte actomyosin and microtubular organization and chemotaxis.

    PubMed

    Vicente-Manzanares, Miguel; Cabrero, José Román; Rey, Mercedes; Pérez-Martínez, Manuel; Ursa, Angeles; Itoh, Kazuyuki; Sánchez-Madrid, Francisco

    2002-01-01

    The possible involvement of the Rho-p160ROCK (Rho coiled-coil kinase) pathway in the signaling induced by the chemokine Stromal cell-derived factor (SDF)-1alpha has been studied in human PBL. SDF-1alpha induced activation of RhoA, but not that of Rac. RhoA activation was followed by p160ROCK activation mediated by RhoA, which led to myosin light chain (MLC) phosphorylation, which was dependent on RhoA and p160ROCK activities. The kinetics of MLC activation was similar to that of RhoA and p160ROCK. The role of this cascade in overall cell morphology and functional responses to the chemokine was examined employing different chemical inhibitors. Inhibition of either RhoA or p160ROCK did not block SDF-1alpha-induced short-term actin polymerization, but induced the formation of long spikes arising from the cell body, which were found to be microtubule based. This morphological change was associated with an increase in microtubule instability, which argues for an active microtubule polymerization in the formation of these spikes. Inhibition of the Rho-p160ROCK-MLC kinase signaling cascade at different steps blocked lymphocyte migration and the chemotaxis induced by SDF-1alpha. Our results indicate that the Rho-p160ROCK axis plays a pivotal role in the control of the cell shape as a step before lymphocyte migration toward a chemotactic gradient.

  7. Quantile Regression with Censored Data

    ERIC Educational Resources Information Center

    Lin, Guixian

    2009-01-01

    The Cox proportional hazards model and the accelerated failure time model are frequently used in survival data analysis. They are powerful, yet have limitation due to their model assumptions. Quantile regression offers a semiparametric approach to model data with possible heterogeneity. It is particularly powerful for censored responses, where the…

  8. Multiple Regression: A Leisurely Primer.

    ERIC Educational Resources Information Center

    Daniel, Larry G.; Onwuegbuzie, Anthony J.

    Multiple regression is a useful statistical technique when the researcher is considering situations in which variables of interest are theorized to be multiply caused. It may also be useful in those situations in which the researchers is interested in studies of predictability of phenomena of interest. This paper provides an introduction to…

  9. Weighting Regressions by Propensity Scores

    ERIC Educational Resources Information Center

    Freedman, David A.; Berk, Richard A.

    2008-01-01

    Regressions can be weighted by propensity scores in order to reduce bias. However, weighting is likely to increase random error in the estimates, and to bias the estimated standard errors downward, even when selection mechanisms are well understood. Moreover, in some cases, weighting will increase the bias in estimated causal parameters. If…

  10. Quantile Regression with Censored Data

    ERIC Educational Resources Information Center

    Lin, Guixian

    2009-01-01

    The Cox proportional hazards model and the accelerated failure time model are frequently used in survival data analysis. They are powerful, yet have limitation due to their model assumptions. Quantile regression offers a semiparametric approach to model data with possible heterogeneity. It is particularly powerful for censored responses, where the…

  11. Correlation Weights in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.; Jones, Jeff A.

    2010-01-01

    A general theory on the use of correlation weights in linear prediction has yet to be proposed. In this paper we take initial steps in developing such a theory by describing the conditions under which correlation weights perform well in population regression models. Using OLS weights as a comparison, we define cases in which the two weighting…

  12. Cactus: An Introduction to Regression

    ERIC Educational Resources Information Center

    Hyde, Hartley

    2008-01-01

    When the author first used "VisiCalc," the author thought it a very useful tool when he had the formulas. But how could he design a spreadsheet if there was no known formula for the quantities he was trying to predict? A few months later, the author relates he learned to use multiple linear regression software and suddenly it all clicked into…

  13. Ridge Regression for Interactive Models.

    ERIC Educational Resources Information Center

    Tate, Richard L.

    1988-01-01

    An exploratory study of the value of ridge regression for interactive models is reported. Assuming that the linear terms in a simple interactive model are centered to eliminate non-essential multicollinearity, a variety of common models, representing both ordinal and disordinal interactions, are shown to have "orientations" that are…

  14. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.

    PubMed

    Tournaye, Herman; Sukhikh, Gennady T; Kahler, Elke; Griesinger, Georg

    2017-05-01

    Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to <42 years of age; body mass index (BMI) ≥18 to ≤30 kg/m2) with a documented history of infertility who were planning to undergo IVF. A centralized electronic system was used for randomization, and the study investigators, sponsor's study team, and subjects remained blinded throughout the study. In total, 1031 subjects were randomized to receive either oral dydrogesterone (n = 520) or MVP (n = 511). Luteal support was started on the day of oocyte retrieval and continued until 12 weeks of gestation (Week 10), if a positive pregnancy test was obtained at 2 weeks after embryo transfer. In the full analysis set (FAS), 497 and 477 subjects in the oral dydrogesterone and MVP groups, respectively, had an embryo transfer. Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates at 12 weeks of gestation of 37.6% and 33.1% in the oral dydrogesterone and MVP treatment groups, respectively (difference 4.7%; 95% CI: -1.2-10.6%). Live birth rates of 34.6% (172 mothers with 213 newborns) and 29

  15. Hierarchical Adaptive Regression Kernels for Regression with Functional Predictors

    PubMed Central

    Woodard, Dawn B.; Crainiceanu, Ciprian; Ruppert, David

    2013-01-01

    We propose a new method for regression using a parsimonious and scientifically interpretable representation of functional predictors. Our approach is designed for data that exhibit features such as spikes, dips, and plateaus whose frequency, location, size, and shape varies stochastically across subjects. We propose Bayesian inference of the joint functional and exposure models, and give a method for efficient computation. We contrast our approach with existing state-of-the-art methods for regression with functional predictors, and show that our method is more effective and efficient for data that include features occurring at varying locations. We apply our methodology to a large and complex dataset from the Sleep Heart Health Study, to quantify the association between sleep characteristics and health outcomes. Software and technical appendices are provided in online supplemental materials. PMID:24293988

  16. The effect of PCB126, 77, and 153 on the intracellular mobilization of Ca+2 in bovine granulosa and luteal cells after FSH and LH surge in vitro.

    PubMed

    Mlynarczuk, J; Kowalik, M

    2013-01-01

    Polychlorinated biphenyls (PCBs) are a group of persistent environmental pollutants that impair cattle reproduction. Among other effects, PCBs can disturb the intracellular mobilization of Ca(+2) in several cell types. Hence, it is possible that they disrupt the transduction of intracellular signals generated from gonadotropin (FSH/LH) receptors. In steroidogenic ovarian cells, a defect in Ca(+2) mobilization may have a detrimental influence on two important processes: the secretion of steroids (E2 or/and P4) and their morphological and functional differentiation. The aim of this study was to determine the influence of PCBs: 126 (dioxin-like) 77 (ambivalent) and 153 (estrogen-like) and a mixture of PCBs (Aroclor 1248) on these processes. Bovine granulosa and luteal cells were incubated for 72 hrs with PCBs (100 ng/ml), followed by Fura 2AM dye, and the fluctuations in intracellular Ca(+2) mobilization after FSH/LH treatment were determined using an inverted microscope coupled with a CCD camera. The intensity and area of fluorescence excited by UV light were detected in the green spectrum of visible light. Aroclor 1248 and PCBs 153 and 77 significantly decreased (P < 0.01-0.001) the effect of FSH on intracellular Ca(+2) mobilization in granulosa cells. In luteal cells, the most effective PCB on this process was PCB 77. The results revealed adverse effects of PCBs on the mobilization of intracellular Ca(+2). Moreover, the estrogen-like congeners were found to more effectively disturb this process than the dioxin-like PCB 126. Hence, it is possible for PCBs to have a negative influence on reproductive processes by affecting calcium mobilization.

  17. Nutritionally induced relationships between insulin levels during the weaning-to-ovulation interval and reproductive characteristics in multiparous sows: II. Luteal development, progesterone and conceptus development and uniformity.

    PubMed

    Wientjes, J G M; Soede, N M; van den Brand, H; Kemp, B

    2012-02-01

    Insulin-stimulating sow diets before mating improve piglet uniformity. We studied effects of nutritionally induced differences in insulin levels during the weaning-to-ovulation interval (WOI) on luteal development, progesterone secretion and pre-implantation conceptus development and uniformity (d10). To create insulin contrasts, 32 multiparous sows were fed either a dextrose plus lactose containing diet (each 150 g/day) at 4 h intervals (DL treatment) or an isocalorically control diet (containing soybean oil) at 12 h intervals (CTRL treatment) during the WOI. After ovulation, all sows received a standard gestation diet at 12 h intervals. Ovulation rate, plasma progesterone levels, pregnancy rate and embryo survival did not differ between treatments. CTRL sows had a higher total luteal weight (11.2 vs 9.7 g; p = 0.03) than DL sows. Conceptus diameter at d10 of pregnancy tended to be larger in CTRL sows (diameter: 7.1 vs 6.4 mm; p = 0.07). Conceptus uniformity was not influenced by treatment. Insulin area under the curve (AUC) and mean insulin during the WOI were positively related with mean progesterone (β values were 0.78 (ng/ml)/1000 μU and 0.14 (ng/ml)/(μU/ml) for AUC and mean, respectively; p < 0.05) and maximal progesterone (β values were 1.46 (ng/ml)/1000 μU and 0.27 (ng/ml)/(μU/ml) for AUC and mean, respectively; p < 0.05) levels during the first 10 days of pregnancy, but not with conceptus development and uniformity. In conclusion, high insulin levels during the WOI seem to be beneficial for progesterone secretion in sows, probably mediated through beneficial effects of insulin on follicle development.

  18. Comparing stimulation requirements and final outcome between early follicular and mid luteal pituitary suppression in the long gonadotropin releasing hormone agonist protocol.

    PubMed

    Sarhan, Abdulmagid; Harira, Mervat; Elshazly, Sherine; Nouh, Ahmad

    2016-05-01

    To compare stimulation requirements and ICSI outcome when agonist treatment is started in the early follicular phase or in mid luteal phase of the cycle. 181 infertile patients were randomly assigned to: group A (N=66) and group B (N=115). GnRH-a (Triptorelin) subcutaneous daily injections started on day 20-22 of the previous cycle till pituitary suppression is achieved where gonadotropins stimulation commenced. In group A, agonist treatment was started on the first or second days of the cycle, in group B it was started on day 20-22 of the cycle. The agonist treatment was continued till the day of (hCG) administration. The stimulation requirements were similar in the two groups. The days of t agonist treatment required to reach pituitary suppression were higher in group A: 12.5±6.4 than in group B, 11±4.5. Days of stimulation (10.4±1.7 and 10.3±1.6) and number of gonadotropin vials (40.1±8.7and 39.3±9.5) did not differ between both groups. The mean number of oocytes retrieved, mean number of embryos produced (11.7±7.4 and 13.3±9.3) (5.9±4.2and 6±5.2) were similar in both groups. The rates of fertilization and cleavage were similar in the two groups. Pregnancy rates were similar in both groups. The clinical pregnancy rates per cycle was 31.8% and 33%, while pregnancy rates per embryo transfer was 36.2 % and 36.5% in groups A and B respectively. Starting pituitary suppression with GnRH agonist in the early follicular phase or mid luteal phase were comparable regarding stimulation requirements and final outcomes.

  19. Development of corpus luteum susceptibility to an analog of prostaglandin F2α, throughout the luteal phase in llamas (Lama glama).

    PubMed

    Bianchi, C P; Cavilla, M V; Jorgensen, E; Benavente, M A; Aba, M A

    2012-04-01

    The aim of the present study was to evaluate the susceptibility of the corpus luteum to d-cloprostenol (synthetic analog of PGF(2α)) throughout the luteal phase in llamas. Female llamas (n=43) were induced to ovulate by GnRH injection in the presence of an ovulatory follicle and randomly assigned into one of six groups: control and treated with an injection of d-cloprostenol on Day 3, 4, 5, 6 or 8 post GnRH. Blood samples were collected to determine plasma progesterone concentrations. There was no effect of treatment on animals injected on Day 3 or 4 post-GnRH. In animals treated on Day 5, different responses were observed. No effect of treatment was recorded in 27% of the animals whereas 55% of the llamas showed a transitory decrease followed by a recovery in plasma progesterone concentrations after d-cloprostenol injection, indicative of a resurgence of the corpus luteum, extending the luteal phase a day more than in control animals. In the remaining 18% of the animals injected on Day 5, (corresponding to those exhibiting the greatest plasma progesterone concentrations at the day of injection), complete luteolysis was observed. Plasma progesterone concentrations decreased to below 1 ng ml(-1) 24 h after d-cloprostenol in llamas injected on Day 6 or 8 post-GnRH. In conclusion, the corpus luteum of llamas is completely refractory to PGF(2α) until Day 4 after induction of ovulation, being partially sensitive by Day 5 and fully responsive to PGF(2α), by Day 6 after induction of ovulation.

  20. Administration of gonadotropin-releasing hormone agonist on Day 5 increases luteal blood flow and improves pregnancy prediction accuracy on Day 14 in recipient Holstein cows

    PubMed Central

    KANAZAWA, Tomomi; SEKI, Motohide; ISHIYAMA, Keiki; ARASEKI, Masao; IZAIKE, Yoshiaki; TAKAHASHI, Toru

    2017-01-01

    This study assessed the effects of gonadotropin-releasing hormone (GnRH) treatment on Day 5 (Day 0 = estrus) on luteal blood flow and accuracy of pregnancy prediction in recipient cows. On Day 5, 120 lactating Holstein cows were randomly assigned to a control group (n = 63) or GnRH group treated with 100 μg of GnRH agonist (n = 57). On Days 3, 5, 7, and 14, each cow underwent ultrasound examination to measure the blood flow area (BFA) and time-averaged maximum velocity (TAMV) at the spiral arteries at the base of the corpus luteum using color Doppler ultrasonography. Cows with a corpus luteum diameter ≥ 20 mm (n = 120) received embryo transfers on Day 7. The BFA values in the GnRH group were significantly higher than those in the control group on Days 7 and 14. TAMV did not differ between these groups. According to receiver operating characteristic analyses to predict pregnancy, a BFA cutoff of 0.52 cm2 yielded the highest sensitivity (83.3%) and specificity (90.5%) on Day 7, and BFA and TAMV values of 0.94 cm2 and 44.93 cm/s, respectively, yielded the highest sensitivity (97.1%) and specificity (100%) on Day 14 in the GnRH group. The areas under the curve for the paired BFA and TAMV in the GnRH group were 0.058 higher than those in the control group (0.996 and 0.938, respectively; P < 0.05). In conclusion, GnRH treatment on Day 5 increased the luteal BFA in recipient cows on Days 7 and 14, and improved the accuracy of pregnancy prediction on Day 14. PMID:28552886

  1. Administration of gonadotropin-releasing hormone agonist on Day 5 increases luteal blood flow and improves pregnancy prediction accuracy on Day 14 in recipient Holstein cows.

    PubMed

    Kanazawa, Tomomi; Seki, Motohide; Ishiyama, Keiki; Araseki, Masao; Izaike, Yoshiaki; Takahashi, Toru

    2017-08-19

    This study assessed the effects of gonadotropin-releasing hormone (GnRH) treatment on Day 5 (Day 0 = estrus) on luteal blood flow and accuracy of pregnancy prediction in recipient cows. On Day 5, 120 lactating Holstein cows were randomly assigned to a control group (n = 63) or GnRH group treated with 100 μg of GnRH agonist (n = 57). On Days 3, 5, 7, and 14, each cow underwent ultrasound examination to measure the blood flow area (BFA) and time-averaged maximum velocity (TAMV) at the spiral arteries at the base of the corpus luteum using color Doppler ultrasonography. Cows with a corpus luteum diameter ≥ 20 mm (n = 120) received embryo transfers on Day 7. The BFA values in the GnRH group were significantly higher than those in the control group on Days 7 and 14. TAMV did not differ between these groups. According to receiver operating characteristic analyses to predict pregnancy, a BFA cutoff of 0.52 cm(2) yielded the highest sensitivity (83.3%) and specificity (90.5%) on Day 7, and BFA and TAMV values of 0.94 cm(2) and 44.93 cm/s, respectively, yielded the highest sensitivity (97.1%) and specificity (100%) on Day 14 in the GnRH group. The areas under the curve for the paired BFA and TAMV in the GnRH group were 0.058 higher than those in the control group (0.996 and 0.938, respectively; P < 0.05). In conclusion, GnRH treatment on Day 5 increased the luteal BFA in recipient cows on Days 7 and 14, and improved the accuracy of pregnancy prediction on Day 14.

  2. Regression Verification Using Impact Summaries

    NASA Technical Reports Server (NTRS)

    Backes, John; Person, Suzette J.; Rungta, Neha; Thachuk, Oksana

    2013-01-01

    Regression verification techniques are used to prove equivalence of syntactically similar programs. Checking equivalence of large programs, however, can be computationally expensive. Existing regression verification techniques rely on abstraction and decomposition techniques to reduce the computational effort of checking equivalence of the entire program. These techniques are sound but not complete. In this work, we propose a novel approach to improve scalability of regression verification by classifying the program behaviors generated during symbolic execution as either impacted or unimpacted. Our technique uses a combination of static analysis and symbolic execution to generate summaries of impacted program behaviors. The impact summaries are then checked for equivalence using an o-the-shelf decision procedure. We prove that our approach is both sound and complete for sequential programs, with respect to the depth bound of symbolic execution. Our evaluation on a set of sequential C artifacts shows that reducing the size of the summaries can help reduce the cost of software equivalence checking. Various reduction, abstraction, and compositional techniques have been developed to help scale software verification techniques to industrial-sized systems. Although such techniques have greatly increased the size and complexity of systems that can be checked, analysis of large software systems remains costly. Regression analysis techniques, e.g., regression testing [16], regression model checking [22], and regression verification [19], restrict the scope of the analysis by leveraging the differences between program versions. These techniques are based on the idea that if code is checked early in development, then subsequent versions can be checked against a prior (checked) version, leveraging the results of the previous analysis to reduce analysis cost of the current version. Regression verification addresses the problem of proving equivalence of closely related program

  3. A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization

    PubMed Central

    Baker, Valerie L.; Jones, Christopher A.; Doody, Kevin; Foulk, Russell; Yee, Bill; Adamson, G. David; Cometti, Barbara; DeVane, Gary; Hubert, Gary; Trevisan, Silvia; Hoehler, Fred; Jones, Clarence; Soules, Michael

    2014-01-01

    STUDY QUESTION Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex®) non-inferior to vaginal progesterone (Endometrin®) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of −2.8% (95% confidence interval (CI) −9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18–42 years, with a BMI of ≤30 kg/m2, with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2–3) FSH of ≤15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS®). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE Using a PP analysis

  4. Interaction Models for Functional Regression

    PubMed Central

    USSET, JOSEPH; STAICU, ANA-MARIA; MAITY, ARNAB

    2015-01-01

    A functional regression model with a scalar response and multiple functional predictors is proposed that accommodates two-way interactions in addition to their main effects. The proposed estimation procedure models the main effects using penalized regression splines, and the interaction effect by a tensor product basis. Extensions to generalized linear models and data observed on sparse grids or with measurement error are presented. A hypothesis testing procedure for the functional interaction effect is described. The proposed method can be easily implemented through existing software. Numerical studies show that fitting an additive model in the presence of interaction leads to both poor estimation performance and lost prediction power, while fitting an interaction model where there is in fact no interaction leads to negligible losses. The methodology is illustrated on the AneuRisk65 study data. PMID:26744549

  5. Astronomical Methods for Nonparametric Regression

    NASA Astrophysics Data System (ADS)

    Steinhardt, Charles L.; Jermyn, Adam

    2017-01-01

    I will discuss commonly used techniques for nonparametric regression in astronomy. We find that several of them, particularly running averages and running medians, are generically biased, asymmetric between dependent and independent variables, and perform poorly in recovering the underlying function, even when errors are present only in one variable. We then examine less-commonly used techniques such as Multivariate Adaptive Regressive Splines and Boosted Trees and find them superior in bias, asymmetry, and variance both theoretically and in practice under a wide range of numerical benchmarks. In this context the chief advantage of the common techniques is runtime, which even for large datasets is now measured in microseconds compared with milliseconds for the more statistically robust techniques. This points to a tradeoff between bias, variance, and computational resources which in recent years has shifted heavily in favor of the more advanced methods, primarily driven by Moore's Law. Along these lines, we also propose a new algorithm which has better overall statistical properties than all techniques examined thus far, at the cost of significantly worse runtime, in addition to providing guidance on choosing the nonparametric regression technique most suitable to any specific problem. We then examine the more general problem of errors in both variables and provide a new algorithm which performs well in most cases and lacks the clear asymmetry of existing non-parametric methods, which fail to account for errors in both variables.

  6. Regression analysis of cytopathological data

    SciTech Connect

    Whittemore, A.S.; McLarty, J.W.; Fortson, N.; Anderson, K.

    1982-12-01

    Epithelial cells from the human body are frequently labelled according to one of several ordered levels of abnormality, ranging from normal to malignant. The label of the most abnormal cell in a specimen determines the score for the specimen. This paper presents a model for the regression of specimen scores against continuous and discrete variables, as in host exposure to carcinogens. Application to data and tests for adequacy of model fit are illustrated using sputum specimens obtained from a cohort of former asbestos workers.

  7. Cinnamaldehyde inhibits the tumor necrosis factor-{alpha}-induced expression of cell adhesion molecules in endothelial cells by suppressing NF-{kappa}B activation: Effects upon I{kappa}B and Nrf2

    SciTech Connect

    Liao, B.-C.; Hsieh, C.-W.; Liu, Y.-C.; Tzeng, T.-T.; Sun, Y.-W.; Wung, B.-S.

    2008-06-01

    The production of adhesion molecules and subsequent attachment of leukocytes to endothelial cells (ECs) are critical early events in atherogenesis. These adhesion molecules thus play an important role in the development of this disease. Recent studies have highlighted the chemoprotective and anti-inflammatory effects of cinnamaldehyde, a Cinnamomum cassia Presl-specific diterpene. In our current study, we have examined the effects of both cinnamaldehyde and extracts of C. cassia on cytokine-induced monocyte/human endothelial cell interactions. We find that these compounds inhibit the adhesion of TNF{alpha}-induced monocytes to endothelial cells and suppress the expression of the cell adhesion molecules, VCAM-1 and ICAM-1, at the transcriptional level. Moreover, in TNF{alpha}-treated ECs, the principal downstream signal of VCAM-1 and ICAM-1, NF-{kappa}B, was also found to be abolished in a time-dependent manner. Interestingly, cinnamaldehyde exerts its anti-inflammatory effects by blocking the degradation of the inhibitory protein I{kappa}B-{alpha}, but only in short term pretreatments, whereas it does so via the induction of Nrf2-related genes, including heme-oxygenase-1 (HO-1), over long term pretreatments. Treating ECs with zinc protoporphyrin, a HO-1 inhibitor, partially blocks the anti-inflammatory effects of cinnamaldehyde. Elevated HO-1 protein levels were associated with the inhibition of TNF{alpha}-induced ICAM-1 expression. In addition to HO-1, we also found that cinnamaldehyde can upregulate Nrf2 in nuclear extracts, and can increase ARE-luciferase activity and upregulate thioredoxin reductase-1, another Nrf2-related gene. Moreover, cinnamaldehyde exposure rapidly reduces the cellular GSH levels in ECs over short term treatments but increases these levels after 9 h exposure. Hence, our present findings indicate that cinnamaldehyde suppresses TNF-induced singling pathways via two distinct mechanisms that are activated by different pretreatment periods.

  8. Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta.

    PubMed

    Tian, Qingping; Miyazaki, Ryohei; Ichiki, Toshihiro; Imayama, Ikuyo; Inanaga, Keita; Ohtsubo, Hideki; Yano, Kotaro; Takeda, Kotaro; Sunagawa, Kenji

    2009-05-01

    Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-gamma. Although peroxisome proliferator-activated receptor-gamma activators have been shown to have an anti-inflammatory effect, such as inhibition of cytokine production, it has not been determined whether telmisartan has such effects. We examined whether telmisartan inhibits expression of interleukin-6 (IL-6), a proinflammatory cytokine, in vascular smooth muscle cells. Telmisartan, but not valsartan, attenuated IL-6 mRNA expression induced by tumor necrosis factor-alpha (TNF-alpha). Telmisartan decreased TNF-alpha-induced IL-6 mRNA and protein expression in a dose-dependent manner. Because suppression of IL-6 mRNA expression was prevented by pretreatment with GW9662, a specific peroxisome proliferator-activated receptor-gamma antagonist, peroxisome proliferator-activated receptor-gamma may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-alpha. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor kappaB and CCAAT/enhancer-binding protein-beta sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-alpha-induced nuclear factor kappaB- and CCAAT/enhancer-binding protein-beta-dependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-alpha-infused mice and IL-6 production from rat aorta stimulated with TNF-alpha ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-alpha in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-alpha and angiotensin II play important roles in atherogenesis through enhancement of vascular inflammation, telmisartan may be beneficial for treatment of not only hypertension but also vascular inflammatory change.

  9. The major acute-phase protein, serum amyloid P component, in mice is not involved in endogenous resistance against tumor necrosis factor alpha-induced lethal hepatitis, shock, and skin necrosis.

    PubMed

    Van Molle, W; Hochepied, T; Brouckaert, P; Libert, C

    2000-09-01

    The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) induces lethal hepatitis when injected into D-(+)-galactosamine-sensitized mice on the one hand or systemic inflammatory response syndrome (SIRS) in normal mice on the other hand. We studied whether serum amyloid P component (SAP), the major acute-phase protein in mice, plays a protective role in both lethal models. For this purpose, we used SAP(0/0) mice generated by gene targeting. We studied the lethal response of SAP(0/0) or SAP(+/+) mice to both lethal triggers but found no differences in the sensitivity of both types of mice. We also investigated whether SAP is involved in establishing two types of endogenous protection: one using a single injection of interleukin-1beta (IL-1beta) for desensitization and clearly involving a liver protein, the other by tolerizing mice for 5 days using small doses of human TNF-alpha. Although after IL-1beta or after tolerization the SAP levels in the serum had risen fourfold in the control mice and not in the SAP(0/0) mice, the same extents of desensitization and tolerization were achieved. Finally, we observed that the induction of hemorrhagic necrosis in the skin of mice by two consecutive local injections with TNF-alpha was not altered in SAP(0/0) mice. We conclude that the presence or absence of SAP has no influence on the sensitivity of mice to TNF-alpha-induced hepatitis, SIRS, and hemorrhagic necrosis or on the endogenous protective mechanisms of desensitization or tolerization.

  10. Quantum algorithm for linear regression

    NASA Astrophysics Data System (ADS)

    Wang, Guoming

    2017-07-01

    We present a quantum algorithm for fitting a linear regression model to a given data set using the least-squares approach. Differently from previous algorithms which yield a quantum state encoding the optimal parameters, our algorithm outputs these numbers in the classical form. So by running it once, one completely determines the fitted model and then can use it to make predictions on new data at little cost. Moreover, our algorithm works in the standard oracle model, and can handle data sets with nonsparse design matrices. It runs in time poly( log2(N ) ,d ,κ ,1 /ɛ ) , where N is the size of the data set, d is the number of adjustable parameters, κ is the condition number of the design matrix, and ɛ is the desired precision in the output. We also show that the polynomial dependence on d and κ is necessary. Thus, our algorithm cannot be significantly improved. Furthermore, we also give a quantum algorithm that estimates the quality of the least-squares fit (without computing its parameters explicitly). This algorithm runs faster than the one for finding this fit, and can be used to check whether the given data set qualifies for linear regression in the first place.

  11. Multiatlas Segmentation as Nonparametric Regression

    PubMed Central

    Awate, Suyash P.; Whitaker, Ross T.

    2015-01-01

    This paper proposes a novel theoretical framework to model and analyze the statistical characteristics of a wide range of segmentation methods that incorporate a database of label maps or atlases; such methods are termed as label fusion or multiatlas segmentation. We model these multiatlas segmentation problems as nonparametric regression problems in the high-dimensional space of image patches. We analyze the nonparametric estimator’s convergence behavior that characterizes expected segmentation error as a function of the size of the multiatlas database. We show that this error has an analytic form involving several parameters that are fundamental to the specific segmentation problem (determined by the chosen anatomical structure, imaging modality, registration algorithm, and label-fusion algorithm). We describe how to estimate these parameters and show that several human anatomical structures exhibit the trends modeled analytically. We use these parameter estimates to optimize the regression estimator. We show that the expected error for large database sizes is well predicted by models learned on small databases. Thus, a few expert segmentations can help predict the database sizes required to keep the expected error below a specified tolerance level. Such cost-benefit analysis is crucial for deploying clinical multiatlas segmentation systems. PMID:24802528

  12. Multiatlas segmentation as nonparametric regression.

    PubMed

    Awate, Suyash P; Whitaker, Ross T

    2014-09-01

    This paper proposes a novel theoretical framework to model and analyze the statistical characteristics of a wide range of segmentation methods that incorporate a database of label maps or atlases; such methods are termed as label fusion or multiatlas segmentation. We model these multiatlas segmentation problems as nonparametric regression problems in the high-dimensional space of image patches. We analyze the nonparametric estimator's convergence behavior that characterizes expected segmentation error as a function of the size of the multiatlas database. We show that this error has an analytic form involving several parameters that are fundamental to the specific segmentation problem (determined by the chosen anatomical structure, imaging modality, registration algorithm, and label-fusion algorithm). We describe how to estimate these parameters and show that several human anatomical structures exhibit the trends modeled analytically. We use these parameter estimates to optimize the regression estimator. We show that the expected error for large database sizes is well predicted by models learned on small databases. Thus, a few expert segmentations can help predict the database sizes required to keep the expected error below a specified tolerance level. Such cost-benefit analysis is crucial for deploying clinical multiatlas segmentation systems.

  13. Relationships among early postpartum luteal activity, parity, and insemination outcomes based on in-line milk progesterone profiles in Canadian Holstein cows.

    PubMed

    Bruinjé, Tony C; Colazo, Marcos G; Gobikrushanth, Mohanathas; Ambrose, Divakar J

    2017-09-15

    The objectives of this retrospective study were to use in-line milk progesterone (mP4) data to investigate relationships of (1) commencement of luteal activity (CLA), and (2) luteal phase (LP) length and frequency preceding first postpartum AI, with parity and AI outcomes in Canadian Holstein cows. Starting 21 ± 1 days postpartum (DPP), levels of mP4 were assessed every 2.2 ± 2.0 d through an automated in-line milk analysis system (Herd Navigator™, DeLaval International, Tumba, Sweden) until ∼55 d after first or second AI in 748 Holstein cows from two herds. The CLA was defined as the DPP of the first of at least two consecutive samples with mP4 ≥5 ng/mL, and the period with elevated mP4 (≥5 ng/mL) was defined as the LP. Cows were categorized by CLA [earlier (≤) or later (>) than 28, 35, 42, 49, 56, and 63 DPP], and by the pattern of LP frequency preceding first AI as having or not: (1) one or more normal LP (LP length ≥7 and ≤19 d); (2) one or more abnormal LP (LP length <7 or >19 d, or interluteal period ≥12 d); and (3) two or more LP (either normal or abnormal). Outcomes of first or second AI were determined by the interval between AI and cessation of the ensuing LP as: non-pregnant (mP4-decline ≤30 d), presumed-pregnant (no mP4-decline until 55 d), or presumed-pregnancy loss (mP4-decline between 31 and ≤55 d). The odds of pregnancy per AI (P/AI) at 55 d and pregnancy loss were evaluated using generalized linear mixed models. Primiparous cows had lower odds of having CLA ≤28 DPP [Odds ratio (OR) = 0.58, P = 0.002] and one or more abnormal LP (OR = 0.73, P = 0.04) than multiparous cows. In multiparous cows, CLA ≤28 DPP decreased pregnancy loss (OR = 0.48, P = 0.05) and CLA ≤56 DPP increased P/AI (OR = 4.69, P < 0.01) compared to a later CLA. Primiparous and multiparous cows that had one or more normal LP before first AI had increased P/AI (OR = 3.85 and 3.45, respectively, P < 0.01) and reduced

  14. Topography-Based Keratoconus Regression.

    PubMed

    Kymionis, George D; Tsoulnaras, Konstantinos I; Grentzelos, Michael A; Shehadeh, Mohammad M; Klados, Nektarios E; Karavitaki, Alexandra A; Kankariya, Vardhaman P; Pallikaris, Ioannis G

    2013-10-01

    To report 3 cases of keratoconic patients who had progressive corneal topographic flattening during a 2-year follow-up period. Case series. Three patients with bilateral keratoconus, each operated for advanced keratoconus in one of their eyes, were observed for possible progression of the disorder for a period of 2 years. During the 2-year follow-up period, topographic examination showed progressive corneal flattening in the nonoperated eye. Mean keratometry decreased in all patients, whereas topography showed significant flattening at the apex of the cone. Best-spectacle-corrected visual acuity increased in one of the patients, whereas the others had stable uncorrected and best-spectacle-corrected visual acuity during the follow-up period. All patients had positive family medical history for diabetes mellitus, but none of them was diabetic. This is the first report of topography-based keratoconus regression during a 2-year follow-up period.

  15. Practical Session: Multiple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    Three exercises are proposed to illustrate the simple linear regression. In the first one investigates the influence of several factors on atmospheric pollution. It has been proposed by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr33.pdf) and is based on data coming from 20 cities of U.S. Exercise 2 is an introduction to model selection whereas Exercise 3 provides a first example of analysis of variance. Exercises 2 and 3 have been proposed by A. Dalalyan at ENPC (see Exercises 2 and 3 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_5.pdf).

  16. Recognition of caudal regression syndrome.

    PubMed

    Boulas, Mari M

    2009-04-01

    Caudal regression syndrome, also referred to as caudal dysplasia and sacral agenesis syndrome, is a rare congenital malformation characterized by varying degrees of developmental failure early in gestation. It involves the lower extremities, the lumbar and coccygeal vertebrae, and corresponding segments of the spinal cord. This is a rare disorder, and true pathogenesis is unclear. The etiology is thought to be related to maternal diabetes, genetic predisposition, and vascular hypoperfusion, but no true causative factor has been determined. Fetal diagnostic tools allow for early recognition of the syndrome, and careful examination of the newborn is essential to determine the extent of the disorder. Associated organ system dysfunction depends on the severity of the disease. Related defects are structural, and systematic problems including respiratory, cardiac, gastrointestinal, urinary, orthopedic, and neurologic can be present in varying degrees of severity and in different combinations. A multidisciplinary approach to management is crucial. Because the primary pathology is irreversible, treatment is only supportive.

  17. Lumbar herniated disc: spontaneous regression

    PubMed Central

    Yüksel, Kasım Zafer

    2017-01-01

    Background Low back pain is a frequent condition that results in substantial disability and causes admission of patients to neurosurgery clinics. To evaluate and present the therapeutic outcomes in lumbar disc hernia (LDH) patients treated by means of a conservative approach, consisting of bed rest and medical therapy. Methods This retrospective cohort was carried out in the neurosurgery departments of hospitals in Kahramanmaraş city and 23 patients diagnosed with LDH at the levels of L3−L4, L4−L5 or L5−S1 were enrolled. Results The average age was 38.4 ± 8.0 and the chief complaint was low back pain and sciatica radiating to one or both lower extremities. Conservative treatment was administered. Neurological examination findings, durations of treatment and intervals until symptomatic recovery were recorded. Laségue tests and neurosensory examination revealed that mild neurological deficits existed in 16 of our patients. Previously, 5 patients had received physiotherapy and 7 patients had been on medical treatment. The number of patients with LDH at the level of L3−L4, L4−L5, and L5−S1 were 1, 13, and 9, respectively. All patients reported that they had benefit from medical treatment and bed rest, and radiologic improvement was observed simultaneously on MRI scans. The average duration until symptomatic recovery and/or regression of LDH symptoms was 13.6 ± 5.4 months (range: 5−22). Conclusions It should be kept in mind that lumbar disc hernias could regress with medical treatment and rest without surgery, and there should be an awareness that these patients could recover radiologically. This condition must be taken into account during decision making for surgical intervention in LDH patients devoid of indications for emergent surgery. PMID:28119770

  18. Conversion of cortisone to cortisol and prostaglandin F2α production by the reproductive tract of cows at the late luteal stage in vivo.

    PubMed

    Duong, H T; Skarzynski, D J; Piotrowska-Tomala, K K; Bah, M M; Jankowska, K; Warmowski, P; Łukasik, K; Okuda, K; Acosta, T J

    2012-12-01

    Previous in vitro studies demonstrated that bovine endometrium has the capacity to convert inactive cortisone to biologically active cortisol (Cr) and that Cr inhibits cytokine-stimulated prostaglandin F(2α) (PGF) production. This study was carried out to test the hypothesis that bovine reproductive tract has the capacity to convert cortisone to Cr in vivo and to evaluate the effects of intravaginal application of exogenous cortisone on uterine PGF secretion during the late luteal stage. The temporal relationships between PGF and Cr levels in uterine plasma were also determined. Catheters were inserted into jugular vein (JV), uterine vein (UV), vena cava caudalis (VCC) and aorta abdominalis (AA) of six cows on Day 15 of the oestrous cycle (ovulation = Day 0) for frequent blood collection. On Day 16, the cows were divided randomly into two groups and infused intravaginally with vaseline gel (10 ml; control; n = 3) or cortisone dissolved in vaseline gel (100 mg; n = 3). Blood samples were collected at -2, -1, -0.5, 0, 0.5, 1, 1.5, 2, 3, 4, 5 and 6 h after treatments (0 h). Intravaginal application of cortisone increased plasma concentrations of Cr between 0.5 and 1.5 h in UV, at 0.5 h in VCC, at 1 h in JV and at 1.5 h in AA. The plasma concentrations of PGF in UV and of PGF metabolite in JV were greater at 0.5 and 1 h in the cortisone-treated animals than in control animals. The levels of PGF in UV blood plasma decreased after Cr reached its highest levels. The overall findings suggest that the female reproductive tract has the capacity to convert cortisone to Cr in vivo. Based on the temporal changes of PGF and Cr levels in the uterine plasma, a biphasic response in PGF secretion was found to be associated to the Cr increase induced by the cortisone treatment at the late luteal stage in non-pregnant cows. © 2012 Blackwell Verlag GmbH.

  19. Relationship between gonadotrophins, inhibin and sex steroid secretion during the periovulatory period and the luteal phase in the blue fox (Alopex lagopus).

    PubMed

    Mondain-Monval, M; Farstad, W; Smith, A J; Roger, M; Lahlou, N

    1993-01-01

    The blue fox is a monestrous seasonal breeder with a pro-oestrus and oestrus lasting several days and a prolonged luteal phase in non-pregnant as well as pregnant vixens. Ovulation occurs 2 days after the preovulatory luteinizing hormone (LH) peak at the onset of oestrus; oocytes are ovulated as primary oocytes and maturation is completed 2-3 days later. Fertilization is possible during all stages of oocyte maturation until degeneration of oocytes 5 or 6 days after the LH peak. In this study, changes in plasma concentrations of follicle-stimulating hormone (FSH) and immunoreactive inhibin (iINH) and their relationships with LH, oestradiol, androstenedione, testosterone and progesterone secretion and with the periovulatory events, were determined throughout the reproductive cycle of 14 vixens. In late anoestrus and pro-oestrus, FSH and iINH were inversely related to each other (r = -0.84, P < 0.001); whereas FSH concentrations declined to reach low values within the 5 days preceding the LH peak, iINH secretion increased, as did that of oestradiol and androgens. Thereafter, iINH and steroid concentrations with the exception of progesterone reached maximal values at the time of the LH and FSH peaks and decreased within the following 2-3 days in the early luteal phase. Progesterone started to increase simultaneously with the LH peak, and when oocyte maturation was completed (around day 4), progesterone concentrations were increasing, while those of other hormones were low. A postovulatory release of FSH was detected between days 6 and 10; it preceded the rise in iINH, which began on day 8 when concentrations of progesterone were already high and those of oestradiol and LH were low. Progesterone and iINH were positively correlated over the period day 6 to day 49 (r = 0.62, P < 0.01). These results indicate that, in the blue fox, iINH is secreted by the preovulatory follicle and the corpus luteum; that during pro-oestrus, iINH may act in synergy with oestradiol to reduce

  20. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization

    PubMed Central

    Tournaye, Herman; Sukhikh, Gennady T.; Griesinger, Georg

    2017-01-01

    Abstract STUDY QUESTION Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? SUMMARY ANSWER Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. WHAT IS KNOWN ALREADY MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. STUDY DESIGN, SIZE, DURATION Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to <42 years of age; body mass index (BMI) ≥18 to ≤30 kg/m2) with a documented history of infertility who were planning to undergo IVF. A centralized electronic system was used for randomization, and the study investigators, sponsor's study team, and subjects remained blinded throughout the study. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 1031 subjects were randomized to receive either oral dydrogesterone (n = 520) or MVP (n = 511). Luteal support was started on the day of oocyte retrieval and continued until 12 weeks of gestation (Week 10), if a positive pregnancy test was obtained at 2 weeks after embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set (FAS), 497 and 477 subjects in the oral dydrogesterone and MVP groups, respectively, had an embryo transfer. Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates at 12 weeks of gestation of 37.6% and 33.1% in

  1. Effect of increasing maximal aerobic exercise on serum gonadal hormones and alpha-fetoprotein in the luteal phase of professional female soccer players.

    PubMed

    Otağ, Aynur; Hazar, Muhsin; Otağ, İlhan; Beyleroğlu, Malik

    2016-03-01

    [Purpose] The performance of female athletes during their menstrual period has attracted the attention of researchers for many years. It is known that the menstrual period changes with exercise. Alpha-fetoprotein (AFP) is an oncofetal protein. In this study, the effect of maximal aerobic exercise in the luteal phase on some hormones and AFP in female athletes was researched. [Subjects and Methods] Twelve volunteers and healthy female footballers with normal menstrual cycles volunteered for this study as subjects. All the participants performed a shuttle run test. Blood samples were taken before, after, and one hour after exercise. Serum AFP, estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) values were measured using an auto analyzer and original kits. Heart rate measurements were performed before and after the exercise. [Results] AFP activity had significantly decreased after 1 h of recovery from the exercise in the female soccer players, and estrogen and LH activity had significantly increased immediately after the exercise. Progesterone activity had significantly decreased immediately after the exercise. FSH values had significantly increased immediately after the exercise. [Conclusion] The results of the present study show there were significant decreases in the values of AFP, which is a cancer parameter, 1 hour after the exercise. This result may be valuable in future physiotherapy studies on the relationship between exercise and cancer.

  2. Streamflow forecasting using functional regression

    NASA Astrophysics Data System (ADS)

    Masselot, Pierre; Dabo-Niang, Sophie; Chebana, Fateh; Ouarda, Taha B. M. J.

    2016-07-01

    Streamflow, as a natural phenomenon, is continuous in time and so are the meteorological variables which influence its variability. In practice, it can be of interest to forecast the whole flow curve instead of points (daily or hourly). To this end, this paper introduces the functional linear models and adapts it to hydrological forecasting. More precisely, functional linear models are regression models based on curves instead of single values. They allow to consider the whole process instead of a limited number of time points or features. We apply these models to analyse the flow volume and the whole streamflow curve during a given period by using precipitations curves. The functional model is shown to lead to encouraging results. The potential of functional linear models to detect special features that would have been hard to see otherwise is pointed out. The functional model is also compared to the artificial neural network approach and the advantages and disadvantages of both models are discussed. Finally, future research directions involving the functional model in hydrology are presented.

  3. Survival analysis and Cox regression.

    PubMed

    Benítez-Parejo, N; Rodríguez del Águila, M M; Pérez-Vicente, S

    2011-01-01

    The data provided by clinical trials are often expressed in terms of survival. The analysis of survival comprises a series of statistical analytical techniques in which the measurements analysed represent the time elapsed between a given exposure and the outcome of a certain event. Despite the name of these techniques, the outcome in question does not necessarily have to be either survival or death, and may be healing versus no healing, relief versus pain, complication versus no complication, relapse versus no relapse, etc. The present article describes the analysis of survival from both a descriptive perspective, based on the Kaplan-Meier estimation method, and in terms of bivariate comparisons using the log-rank statistic. Likewise, a description is provided of the Cox regression models for the study of risk factors or covariables associated to the probability of survival. These models are defined in both simple and multiple forms, and a description is provided of how they are calculated and how the postulates for application are checked - accompanied by illustrating examples with the shareware application R.

  4. Estimating equivalence with quantile regression

    USGS Publications Warehouse

    Cade, B.S.

    2011-01-01

    Equivalence testing and corresponding confidence interval estimates are used to provide more enlightened statistical statements about parameter estimates by relating them to intervals of effect sizes deemed to be of scientific or practical importance rather than just to an effect size of zero. Equivalence tests and confidence interval estimates are based on a null hypothesis that a parameter estimate is either outside (inequivalence hypothesis) or inside (equivalence hypothesis) an equivalence region, depending on the question of interest and assignment of risk. The former approach, often referred to as bioequivalence testing, is often used in regulatory settings because it reverses the burden of proof compared to a standard test of significance, following a precautionary principle for environmental protection. Unfortunately, many applications of equivalence testing focus on establishing average equivalence by estimating differences in means of distributions that do not have homogeneous variances. I discuss how to compare equivalence across quantiles of distributions using confidence intervals on quantile regression estimates that detect differences in heterogeneous distributions missed by focusing on means. I used one-tailed confidence intervals based on inequivalence hypotheses in a two-group treatment-control design for estimating bioequivalence of arsenic concentrations in soils at an old ammunition testing site and bioequivalence of vegetation biomass at a reclaimed mining site. Two-tailed confidence intervals based both on inequivalence and equivalence hypotheses were used to examine quantile equivalence for negligible trends over time for a continuous exponential model of amphibian abundance. ?? 2011 by the Ecological Society of America.

  5. Principal component regression analysis with SPSS.

    PubMed

    Liu, R X; Kuang, J; Gong, Q; Hou, X L

    2003-06-01

    The paper introduces all indices of multicollinearity diagnoses, the basic principle of principal component regression and determination of 'best' equation method. The paper uses an example to describe how to do principal component regression analysis with SPSS 10.0: including all calculating processes of the principal component regression and all operations of linear regression, factor analysis, descriptives, compute variable and bivariate correlations procedures in SPSS 10.0. The principal component regression analysis can be used to overcome disturbance of the multicollinearity. The simplified, speeded up and accurate statistical effect is reached through the principal component regression analysis with SPSS.

  6. Embryonic resorption in context to intragestational corpus luteum regression: a longitudinal ultrasonographic study in the European brown hare (Lepus europaeus PALLAS, 1778).

    PubMed

    Schroeder, K; Drews, B; Roellig, K; Goeritz, F; Hildebrandt, T B

    2013-09-15

    Embryonic resorption is frequently observed in polytocous mammals. Often it occurs as partial litter resorption affecting only single conceptuses of a whole litter. The aim of the study was to describe the incidence and morphology of embryonic resorption in the European brown hare (Lepus europaeus). In 154 pregnancies viable conceptuses, conceptuses undergoing resorption and CL of pregnancy were ultrasonographically monitored during the entire gestation period. Resorptions were classified into (1) "pre-implantation resorptions," (2) "peri-implantation resorptions," and (3) "post-implantation resorptions." The incidence of resorption in the pre-implantation period was 9%, in the peri-implantation period 9%, and in the post-implantation period 24%. Post-implantation resorptions were found up to late pregnancy stages when fetal development was already in progress. The highest daily incidence of resorption was on Day 8 of the 42-day pregnancy. In 91% of the cases, the regression of one CL was observed, while an embryo was undergoing resorption at the same time. The number of resorptions did not significantly differ from the number of CL in regression during gestation, suggesting an interesting one-resorption-to-one-regression relationship. The ultrasonographic appearance of the luteal regression during pregnancy was similar to the morphology characteristic for postpartal luteolysis. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Genetics Home Reference: caudal regression syndrome

    MedlinePlus

    ... of a genetic condition? Genetic and Rare Diseases Information Center Frequency Caudal regression syndrome is estimated to occur in 1 to ... parts of the skeleton, gastrointestinal system, and genitourinary ... caudal regression syndrome results from the presence of an abnormal ...

  8. Common pitfalls in statistical analysis: Logistic regression.

    PubMed

    Ranganathan, Priya; Pramesh, C S; Aggarwal, Rakesh

    2017-01-01

    Logistic regression analysis is a statistical technique to evaluate the relationship between various predictor variables (either categorical or continuous) and an outcome which is binary (dichotomous). In this article, we discuss logistic regression analysis and the limitations of this technique.

  9. Semiparametric regression during 2003–2007*

    PubMed Central

    Ruppert, David; Wand, M.P.; Carroll, Raymond J.

    2010-01-01

    Semiparametric regression is a fusion between parametric regression and nonparametric regression that integrates low-rank penalized splines, mixed model and hierarchical Bayesian methodology – thus allowing more streamlined handling of longitudinal and spatial correlation. We review progress in the field over the five-year period between 2003 and 2007. We find semiparametric regression to be a vibrant field with substantial involvement and activity, continual enhancement and widespread application. PMID:20305800

  10. Effect of genetic merit for energy balance on luteal activity and subsequent reproductive performance in primiparous Holstein-Friesian cows.

    PubMed

    von Leesen, R; Tetens, J; Stamer, E; Junge, W; Thaller, G; Krattenmacher, N

    2014-02-01

    Postpartum energy status is critically important to fertility. However, studies dealing with the relationship between both traits are rare and most refer only to the phenotypic level. In this study, random regression models were used to generate cow-specific lactation curves for daily breeding values (BV) of energy balance (EB) to assess the effect of genetic merit for energy status on different traits derived from progesterone profiles and on subsequent reproductive performance of high-producing dairy cows. Individual feed intake, milk yield, and live weight were recorded for lactation d 11 to 180, and EB was estimated on a daily basis. The results provided the basis for the estimation of BV for 824 primiparous Holstein-Friesian cows. For a subset of these cows (n = 334), progesterone profiles for the resumption of ovarian activity were available. Four different traits describing the genetic merit for EB were defined to evaluate their relationship with fertility. Two EB traits referred to the period in which the average daily EB across all cows was negative (d 11 to 55 postpartum), and 2 parameters were designed considering only daily BV for d 11 to 180 in lactation that were negative. We found that cows with a high genetic merit for EB had a significantly earlier resumption of ovarian activity postpartum. Thus, an EB (indicator) trait should be included in future breeding programs to reduce the currently prolonged anovulatory intervals after parturition. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Regression Analysis by Example. 5th Edition

    ERIC Educational Resources Information Center

    Chatterjee, Samprit; Hadi, Ali S.

    2012-01-01

    Regression analysis is a conceptually simple method for investigating relationships among variables. Carrying out a successful application of regression analysis, however, requires a balance of theoretical results, empirical rules, and subjective judgment. "Regression Analysis by Example, Fifth Edition" has been expanded and thoroughly…

  12. Synthesizing Regression Results: A Factored Likelihood Method

    ERIC Educational Resources Information Center

    Wu, Meng-Jia; Becker, Betsy Jane

    2013-01-01

    Regression methods are widely used by researchers in many fields, yet methods for synthesizing regression results are scarce. This study proposes using a factored likelihood method, originally developed to handle missing data, to appropriately synthesize regression models involving different predictors. This method uses the correlations reported…

  13. Regression Analysis by Example. 5th Edition

    ERIC Educational Resources Information Center

    Chatterjee, Samprit; Hadi, Ali S.

    2012-01-01

    Regression analysis is a conceptually simple method for investigating relationships among variables. Carrying out a successful application of regression analysis, however, requires a balance of theoretical results, empirical rules, and subjective judgment. "Regression Analysis by Example, Fifth Edition" has been expanded and thoroughly…

  14. Developmental Regression in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rogers, Sally J.

    2004-01-01

    The occurrence of developmental regression in autism is one of the more puzzling features of this disorder. Although several studies have documented the validity of parental reports of regression using home videos, accumulating data suggest that most children who demonstrate regression also demonstrated previous, subtle, developmental differences.…

  15. Standards for Standardized Logistic Regression Coefficients

    ERIC Educational Resources Information Center

    Menard, Scott

    2011-01-01

    Standardized coefficients in logistic regression analysis have the same utility as standardized coefficients in linear regression analysis. Although there has been no consensus on the best way to construct standardized logistic regression coefficients, there is now sufficient evidence to suggest a single best approach to the construction of a…

  16. Standards for Standardized Logistic Regression Coefficients

    ERIC Educational Resources Information Center

    Menard, Scott

    2011-01-01

    Standardized coefficients in logistic regression analysis have the same utility as standardized coefficients in linear regression analysis. Although there has been no consensus on the best way to construct standardized logistic regression coefficients, there is now sufficient evidence to suggest a single best approach to the construction of a…

  17. Bayesian Unimodal Density Regression for Causal Inference

    ERIC Educational Resources Information Center

    Karabatsos, George; Walker, Stephen G.

    2011-01-01

    Karabatsos and Walker (2011) introduced a new Bayesian nonparametric (BNP) regression model. Through analyses of real and simulated data, they showed that the BNP regression model outperforms other parametric and nonparametric regression models of common use, in terms of predictive accuracy of the outcome (dependent) variable. The other,…

  18. Synthesizing Regression Results: A Factored Likelihood Method

    ERIC Educational Resources Information Center

    Wu, Meng-Jia; Becker, Betsy Jane

    2013-01-01

    Regression methods are widely used by researchers in many fields, yet methods for synthesizing regression results are scarce. This study proposes using a factored likelihood method, originally developed to handle missing data, to appropriately synthesize regression models involving different predictors. This method uses the correlations reported…

  19. Developmental regression in autism spectrum disorder.

    PubMed

    Al Backer, Nouf Backer

    2015-01-01

    The occurrence of developmental regression in autism spectrum disorder (ASD) is one of the most puzzling phenomena of this disorder. A little is known about the nature and mechanism of developmental regression in ASD. About one-third of young children with ASD lose some skills during the preschool period, usually speech, but sometimes also nonverbal communication, social or play skills are also affected. There is a lot of evidence suggesting that most children who demonstrate regression also had previous, subtle, developmental differences. It is difficult to predict the prognosis of autistic children with developmental regression. It seems that the earlier development of social, language, and attachment behaviors followed by regression does not predict the later recovery of skills or better developmental outcomes. The underlying mechanisms that lead to regression in autism are unknown. The role of subclinical epilepsy in the developmental regression of children with autism remains unclear.

  20. Formation and regression of the corpus luteum of the American alligator

    USGS Publications Warehouse

    Guillette, L.J.; Woodward, A.R.; You-Xiang, Q.; Cox, M.C.; Matter, J.H.; Gross, T.S.

    1995-01-01

    Luteal morphology of the American alligator is unique when compared to other reptiles but is similar to that of its phylogenetic relatives, the birds. The theca is extensively hypertrophied, but the granulosa never fills the cavity formed following the ovulation of the ovum. The formation of the corpus luteum (CL) is correlated with elevated plasma progesterone concentrations, which decline dramatically after oviposition with the onset of luteolysis. Unlike those of most other reptiles, the central luteal cell mass is composed of two cell types; one presumably is derived from the granulosa, whereas the other is from the theca interna. Both cell types are present throughout gravidity but only one cell type is seen during mid to late luteolysis. A significant decline in luteal volume occurs following oviposition and continues throughout the post-oviposition period. The fastest decline in luteal volume occurs in the month immediately after oviposition; this rate then slows. Luteolysis appears to continue for a year or more following oviposition, as distinct structures of luteal origin can still be identified in animals 9 months after oviposition. The size of persistent CL can be used to determine whether a given female oviposited during the previous nesting season. Females with CL having volumes greater than 0.2 cm2 or CL diameters greater than 0.4 cm were active the previous season. 

  1. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection.

    PubMed

    Bergh, Christina; Lindenberg, Svend

    2012-12-01

    SUMMARY QUESTION: Is vaginal progesterone gel equivalent to vaginal micronized progesterone tablets concerning ongoing pregnancy rate and superior concerning patient convenience when used for luteal support after IVF/ICSI? Equivalence of treatments in terms of ongoing live intrauterine pregnancy rate has not been demonstrated; the 95% confidence interval (CI) for the difference in ongoing pregnancy rate (-8.2 to 0.1%) did not lie entirely within the pre-specified equivalence interval -7 to 7%. No significant differences in clinical pregnancy rates have been observed between vaginal progesterone gel and other vaginal progesterone products in earlier studies. However, all previous studies included a limited number of patients. This was a randomized, multicentre, controlled, assessor-blinded equivalence trial in 18 fertility centres in Denmark and Sweden between March 2006 and January 2010. A web-based randomization program was used with concealed allocation of patients. Patients were randomized to one of two groups: vaginal progesterone gel or vaginal micronized progesterone tablets. There was no blinding of patients. A total of 2057 women ≤ 40 years of age were included and down-regulated, using the long agonist protocol and rFSH for stimulation. Luteal support was given for 19 days after embryo transfer or until a negative pregnancy test Day 14 after embryo transfer. Patient convenience was assessed using questionnaires to be filled in 14 days after embryo transfer, before pregnancy test. Ongoing intrauterine pregnancy rates were 299/991 (30.2%) (95% CI 27.3-33.0%) in the progesterone gel group and 324/992 (32.7%) (29.7-35.6%) in the micronized progesterone tablet group. The difference in ongoing pregnancy rates between the groups was -4.1% (-8.2 to 0.1%) and the difference in live birth rates was -3.4% (-7.4 to 0.7%), both calculated after correction for significant confounders. Patient convenience and ease of use (1 = very convenient, 10 = very inconvenient

  2. The relationship between fatty acid profiles in milk identified by Fourier transform infrared spectroscopy and onset of luteal activity in Norwegian dairy cattle.

    PubMed

    Martin, A D; Afseth, N K; Kohler, A; Randby, Å; Eknæs, M; Waldmann, A; Dørum, G; Måge, I; Reksen, O

    2015-08-01

    To investigate the feasibility of milk fatty acids as predictors of onset of luteal activity (OLA), 87 lactations taken from 73 healthy Norwegian Red cattle were surveyed over 2 winter housing seasons. The feasibility of using frozen milk samples for dry-film Fourier transform infrared (FTIR) determination of milk samples was also tested. Morning milk samples were collected thrice weekly (Monday, Wednesday, Friday) for the first 10 wk in milk (WIM). These samples had bronopol (2-bromo-2-nitropropane-1,3-diol) added to them before being frozen at -20°C, thawed, and analyzed by ELISA to determine progesterone concentration and the concentrations of the milk fatty acids C4:0, C14:0, C16:0, C18:0, and cis-9 C18:1 as a proportion of total milk fatty acid content using dry-film FTIR, and averaged by WIM. Onset of luteal activity was defined as the first day that milk progesterone concentrations were >3 ng/mL for 2 successive measurements; the study population was categorized as early (n=47) or late (n=40) OLA, using the median value of 21 DIM as the cutoff. Further milk samples were collected 6 times weekly, from morning and afternoon milkings, these were pooled by WIM, and one proportional sample was analyzed fresh for fat, protein, and lactose content by the dairy company Tine SA, using traditional FTIR spectrography in the wet phase of milk. Daily energy-balance calculations were performed in 42 lactations and averaged by WIM. Animals experiencing late OLA had a more negative energy balance in WIM 1, 3, 4, and 5, with the greatest differences been seen in WIM 3 and 4. A higher proportion of the fatty acids were medium chained, C14:0 and C16:0, in the early than in the late OLA group from WIM 1. In WIM 4, the proportion of total fatty acid content that was C16:0 predicted late OLA, with 74% sensitivity and 80% specificity. The long-chain proportion of the fatty acids C18:0 and cis-9 C18:1 were lower in the early than in the late OLA group. Differences were greatest in

  3. Role of interleukin-1β in the regulation of porcine corpora lutea during the late luteal phase of the cycle and during pregnancy.

    PubMed

    Zmijewska, Agata; Franczak, Anita; Kotwica, Genowefa

    2012-09-01

    Interleukin-1β (IL-1β) may regulate ovarian physiology. In this study, the influence of IL-1β on secretory activity within the corpora lutea (CL) of cyclic and gravid pigs was determined in vitro during different stages of the CL lifespan, e.g. on Days 10-11, 12-13 and 15-16 of the oestrous cycle and pregnancy. IL-1β (10 ng/ml) increased prostaglandin E2 (PGE2) secretion from CL of the cyclic and gravid pigs during studied days of the oestrous cycle and pregnancy. Increase (P < 0.05) of prostaglandin F2α (PGF2α) in IL-1β-treated CL was demonstrated only on Days 10-11 of the oestrous cycle. More potent stimulatory effect of IL-1β on PGE2 than PGF2α secretion resulted in the enhancement of the PGE2:PGF2α ratio in cyclic and early pregnant CL. IL-1β increased (P < 0.05) progesterone (P4) secretion only in gravid CL and had no effect on oestradiol-17β (E2) release. Expression of cyclooxygenase-2 (COX-2) mRNA was stimulated (P < 0.05) in IL-1β-treated cyclic and gravid CL. Expression of prostaglandin synthase mRNAs in response to IL-1β did not increase. In conclusion, IL-1β modulates PGE2, PGF2α and P4 secretion from porcine CL, depending on luteal stage and the surrounding hormonal milieu. The cytokine may act locally in porcine CL for luteotrophic support throughout the PGE2-mediated synthesis and secretion.

  4. [Administering GnRH Agonists in the luteal phase of Artificial Cycle Frozen-Thawed Embryo Transfers. A prospective randomized study].

    PubMed

    Gogce, M; Benchaib, M; Hadj, S; Bordes, A; du Menildot, P; Lornage, J; Salle, B

    2015-11-01

    Adding GnRH agonists in the luteal phase has recently been said to improve implantation in IVF treatment (increased rates of pregnancy and birth). Adding GnRH agonists could also be beneficial for frozen-thawed embryo transfers. The objective was to compare the administration of Gonadotropin Releasing Hormone (GnRH) agonists during implantation with usual progesterone supplementation in the artificial cycle of frozen-thawed embryo transfers. A prospective randomized controlled trial was conducted in a reproductive medicine center in a university hospital including all women starting an artificial cycle of Frozen-Thawed Embryo Transfers (FET). Two hundred and twenty women were randomized from September 2013 to June 2014. In the addition of GnRh agonists' group, two triptorelin injections of 0.1mg were carried out on the 4th day and on the 6th day following the introduction of progesterone. The primary outcome was the ongoing pregnancy rate. The ongoing pregnancy rate was higher (17 % versus 10.6 % P=0.29) when triptorelin was added, although the difference wasn't significant for the population as a whole. The increase proved to be significant in the case of day 2 embryos (34.6 % versus 10.3 % P<0.05) and of vitrified blastocysts (33.3% versus 12.5% P<0.05). The ongoing pregnancy rate for day 2 embryos and vitrified blastocysts significantly increased when GnRH agonists were added during implantation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. Impact of buserelin acetate or hCG administration on day 5 post-ovulation on subsequent luteal profile and conception rate in Murrah buffalo (Bubalus bubalis).

    PubMed

    Pandey, A K; Dhaliwal, G S; Ghuman, S P S; Agarwal, S K

    2015-11-01

    The present study aimed to establish the impact of buserelin acetate or hCG administration on day 5 post-ovulation on subsequent luteal profile and conception rate in buffalo. The buffalo (n=45) were subjected to an estrous synchronization protocol (synthetic analog of PGF2α administered, through intramuscular route, 11 days apart), followed by artificial insemination (AI) during mid to late estrus. On day 5 post-ovulation, buffalo were administered (i.m.) normal saline (Control, n=14), buserelin acetate (20μg, d5-BA, n=14) or human chorionic gonadotropin (3000IU, d5-hCG, n=17). Ovarian ultrasonography was conducted on the day of induced estrus and on days 0, 5, 12, 16 and 21 post-ovulation to assess preovulatory follicle or corpus luteum (CL) diameter. Also, on these days, jugular vein blood sampling was conducted for the estimation of plasma progesterone. First service conception rate was greater (χ(2)=5.18, P>0.05) in d5-BA and d5-hCG groups (71.4% and 47.1%, respectively) as compared to control (28.6%). Both treatment groups had a greater (P<0.05) CL diameter and plasma progesterone during the post-treatment period in comparison to that control treatment group. Treatment-induced accessory CL formation was observed in 92.9% and 76.5% buffalo of d5-BA and d5-hCG groups, respectively. In conclusion, buserelin acetate and hCG administration on day 5 post-ovulation leads to accessory CL formation that may have a role in enhancing conception rate. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. The effect of treatment with flunixin meglumine at different times relative to hCG administration on ovulation failure and luteal function in mares.

    PubMed

    Cuervo-Arango, J

    2011-08-01

    Flunixin meglumine (FM), a prostaglandin synthetase inhibitor, causes ovulatory failure in the mare. However, the effect of the FM treatment relative to the time of hCG administration on the ovulation failure has not been determined nor has its effect on the luteal function of treated mares. Estrous mares with a follicle ≥32 mm (range of 32-38 mm) were treated with 1.7 mg/kg b.w. of FM iv at zero, 12, 24 and 36 h (n=6), at 24 and 36 h (n=6), at 28 and 36 h (n=6), at 24h (n=6) or at 30 h (n=6) after treatment with 1500 IU hCG. One group received no FM (control, n=6). Progesterone concentrations were determined using RIA. Mares treated with FM 0-36 h and 24-36 h had higher (P<0.05) incidence of ovulatory failure (83 and 80%, respectively) than mares treated twice at 28 and 36 h, or once at 24 or at 30 h after hCG (16.7, 0 and 0%, respectively). The anovulatory follicles of FM treated mares luteinized and produced progesterone (>2 ng/ml). The progesterone concentration was lower in mares treated with FM at zero to 36 h and at 24-36 h after hCG than in the other groups. In conclusion, the FM administration was effective in blocking ovulation only when the treatment began ≤24 h after hCG and was continued every 12 h until ≥36 h. In addition, the FM-induced anovulatory follicles underwent luteinization of follicular cells with active production of progesterone. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Maintenance of the corpus luteum of early pregnancy in the ewe. IV. Changes in luteal sensitivity to prostaglandin F2 alpha throughout early pregnancy.

    PubMed

    Silvia, W J; Niswender, G D

    1986-10-01

    Two experiments were conducted to examine the temporal aspects of luteal resistance to the luteolytic effect of prostaglandin (PG) F2 alpha during early pregnancy. In Exp. 1, 14 pregnant and 12 nonpregnant ewes were treated with PGF2 alpha either on d 10 or 13 post-estrus. Jugular venous blood samples were collected at -30 min, 0, 6, 12, 18, 24, 30 and 36 h post-injection for quantification of progesterone. The difference (delta P) between pre-treatment and post-treatment concentrations of progesterone was calculated for each ewe. There was a significant interaction between pregnancy status and day of treatment on delta P (P less than .05). Pregnant and nonpregnant ewes treated on d 10 showed a large delta P. A large delta P also was observed in nonpregnant ewes treated on d 13 post-estrus. However, delta P in pregnant ewes treated on d 13 was smaller than in the other three groups (P less than .05). The temporal patterns of concentrations of progesterone in serum were different among treatment groups (P less than .05). A suppression in the concentration of progesterone was observed by 24 h post-injection in all four treatment groups. Progesterone returned to pre-treatment levels only in pregnant ewes treated on d 13. In Exp. 2, 47 pregnant ewes were treated with PGF2 alpha on d 10, 13, 16, 19, 22, 26 or 30 postestrus. Blood samples were collected and data were analyzed as described for Exp. 1.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial.

    PubMed

    Urman, B; Ata, B; Yakin, K; Alatas, C; Aksoy, S; Mercan, R; Balaban, B

    2009-07-01

    The pathology underlying recurrent implantation failures (RIF) is not clear and treatment options proposed are generally not evidence based. Although the effect of heparin on trophoblast biology has not been studied extensively, given the available data suggesting a possible beneficial effect of heparin on embryo implantation, we decided to undertake this pilot study. One hundred and fifty women with > or =2 failed assisted reproduction treatment cycles were included in this randomized open-label pilot trial. Participants underwent controlled ovarian stimulation with the long protocol and were randomly allocated to receive 1 mg/kg/day low molecular weight heparin (LMWH) or no treatment in addition to routine luteal phase support (LPS) on the day after oocyte retrieval. LPS and LMWH was continued up to the 12th gestational week in pregnant participants. There were 26 (34.7%) live births in the LMWH group, and 20 (26.7%) in the control group (absolute difference 8.0%, 95% CI -4.2 to 24.9%, P = 0.29). There were 34 (45.3%) and 29 (38.7%) clinical pregnancies in the LMWH and control groups, respectively (absolute difference 6.6%, 95% CI -9.0 to 21.8%, P = 0.41). Implantation rates were 24.5 and 19.8% in the LMWH and control groups, respectively (absolute difference 4.7%, 95% CI -4.7 to 14.1%, P = 0.33). Despite lack of statistical significance, observed relative increase by 30% in live birth rates with LMWH may be regarded as a clinically significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment. Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study.

  9. Effect of exogenous progesterone administration on luteal sensitivity to PGF during the early development of the corpus luteum in mares and cows.

    PubMed

    Garcia-Muñoz, A; Valldecabres-Torres, X; Newcombe, J R; Cuervo-Arango, J; Garcia-Rosello, E

    2017-07-25

    The objective of this study was to determine the effect of exogenous progesterone administration at ovulation and during the early development of the CL, on its future sensitivity to a single administration of PGF2a in mares and cows. Horse Retrospective reproductive data from an equine clinic in the UK during three breeding seasons were used. Mares were divided into: control group, cycles with single ovulations; double ovulation group cycles with asynchronous double ovulations; and PRID group: cycles with single ovulations and treatment with intravaginal progesterone device (CIDR) immediately after the ovulation. All mares were treated with d-cloprostenol (PGF) at either: (i) 88 hr; (ii) 96 hr; (iii) 104 hr; or (iv) 112 hr after the last ovulation. Cattle A total of nine non-lactating Holstein cows were used. All cows were administered PGF14 d apart and allocated to one of two groups control group GnRH was administered 56 hr after the second PGF administration. CIDR group CIDR was inserted at the same time of GnRH administration. All cows were administered PGF at 120 hr post-ovulation. The complete luteolysis rate of mares with double ovulation (66.7%) and those treated with exogenous progesterone (68.4%) was significantly higher than the rate of mares with single ovulation (35.6%) at 104 hr. In the cow, however, the treatment with CIDR did not increase the luteolytic response in cows treated at 120 hr post-ovulation. In conclusion, the degree of complete luteolysis can be influenced by increasing the concentration of progesterone during the early luteal development in mares. © 2017 Blackwell Verlag GmbH.

  10. The influence of polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and its metabolite-dichlorodiphenyldichloroethylene (DDE) on mRNA expression for NP-I/OT and PGA, involved in oxytocin synthesis in bovine granulosa and luteal cells.

    PubMed

    Mlynarczuk, Jaroslaw; Wrobel, Michal H; Kotwica, Jan

    2009-11-01

    The effect of polychlorinated biphenyls (PCBs) congeners (PCB 77, PCB 126, PCB 153) and their technical mixture-Aroclor (Ar) 1248, as well as dichlorodiphenyltrichloroethane (DDT) and its metabolite-dichlorodiphenyldichloroethylene (DDE; two individual isomers p,p'- and o,p'- or their mixture, 95% and 5%, respectively) at the dose of 10 ng/ml each, on the gene expression of (a) oxytocin (OT) precursor-neurophysin-oxytocin (NP-I/OT) and (b) peptidyl glycine-alpha-amidating mono-oxygenase (PGA), the terminal enzyme in the pathway of OT synthesis, was studied. Granulosa cells from follicles >1cm in diameter, collected on days 19-21 of estrous cycle, and luteal cells from corpora lutea (CL) collected on days 8-12 of the estrous cycle were used. The cells were incubated (6h) with these xenobiotics and the expression of NP-I/OT and PGA genes was determined. All PCBs increased (P<0.05) NP-I/OT gene expression in granulosa cells. Similarly, all PCBs but PCB 126 increased (P<0.05) PGA gene expression in these cells. DDT and DDE increased (P<0.05) gene expression of NP-I/OT in granulosa cells, while gene expression of PGA in these cells was stimulated (P<0.05) by DDE only. The mRNA expression for NP-I/OT and PGA in luteal cells was increased (P<0.05) by PCB 77 and PCB 153. Both DDE isomers and mixture also stimulated (P<0.05) of NP-I/OT mRNA expression, while increase (P<0.05) of PGA mRNA expression was elicited by incubation of these cells with DDE mixture and Ar 1248. Obtained data suggest that PCBs, DDT and DDE can affect the mRNA expression for NP-I/OT and PGA in bovine granulosa and luteal cells.

  11. Expression of the GnRH and GnRH receptor (GnRH-R) genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland of anestrous and luteal phase ewes.

    PubMed

    Ciechanowska, Magdalena; Lapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

    2008-11-01

    Data exists showing that seasonal changes in the innervations of GnRH cells in the hypothalamus and functions of some neural systems affecting GnRH neurons are associated with GnRH release in ewes. Consequently, we put the question as to how the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland is reflected with LH secretion in anestrous and luteal phase ewes. Analysis of GnRH gene expression by RT-PCR in anestrous ewes indicated comparable levels of GnRH mRNA in the preoptic area, anterior and ventromedial hypothalamus. GnRH-R mRNA at different concentrations was found throughout the preoptic area, anterior and ventromedial hypothalamus, stalk/median eminence and in the anterior pituitary gland. The highest GnRH-R mRNA levels were detected in the stalk/median eminence and in the anterior pituitary gland. During the luteal phase of the estrous cycle in ewes, the levels of GnRH mRNA and GnRH-R mRNA in all structures were significantly higher than in anestrous ewes. Also LH concentrations in blood plasma of luteal phase ewes were significantly higher than those of anestrous ewes. In conclusion, results from this study suggest that low expression of the GnRH and GnRH-R genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland, amongst others, may be responsible for a decrease in LH secretion and the anovulatory state in ewes during the long photoperiod.

  12. Progestin and AdipoQ Receptor 7, Progesterone Membrane Receptor Component 1 (PGRMC1), and PGRMC2 and Their Role in Regulating Progesterone's Ability to Suppress Human Granulosa/Luteal Cells from Entering into the Cell Cycle.

    PubMed

    Sueldo, Carolina; Liu, Xiufang; Peluso, John J

    2015-09-01

    The present studies were designed to determine the role of progesterone receptor membrane component 1 (PGRMC1), PGRMC2, progestin and adipoQ receptor 7 (PAQR7), and progesterone receptor (PGR) in mediating the antimitotic action of progesterone (P4) in human granulosa/luteal cells. For these studies granulosa/luteal cells of 10 women undergoing controlled ovarian hyperstimulation were isolated, maintained in culture, and depleted of PGRMC1, PGRMC2, PAQR7, or PGR by siRNA treatment. The rate of entry into the cell cycle was assessed using the FUCCI cell cycle sensor to determine the percentage of cells in the G1/S stage of the cell cycle. PGRMC1, PGRMC2, PAQR7, and PGR mRNA levels were assessed by real-time PCR and their interactions monitored by in situ proximity ligation assays (PLAs). These studies revealed that PGRMC1, PGRMC2, PAQR7, and PGR were expressed by granulosa/luteal cells from all patients, with PGRMC1 mRNA being most abundant, followed by PAQR7, PGRMC2, and PGR. However, their mRNA levels showed considerable patient variation. P4's ability to suppress entry into the cell cycle was dependent on PGRMC1, PGRMC2, and PAQR7 but not PGR. Moreover, PLAs indicated that PGRMC1, PGRMC2, and PAQR7 formed a complex within the cytoplasm. Based on these studies, it is proposed that these three P4 mediators form a complex within the cytoplasm that is required for P4's action. Moreover, P4's ability to regulate human follicle development may be dependent in part on the expression levels of each of these P4 mediators.

  13. Difference in expression between AQP1 and AQP5 in porcine endometrium and myometrium in response to steroid hormones, oxytocin, arachidonic acid, forskolin and cAMP during the mid-luteal phase of the estrous cycle and luteolysis.

    PubMed

    Skowronska, Agnieszka; Mlotkowska, Patrycja; Nielsen, Soren; Skowronski, Mariusz T

    2015-12-01

    Recently, we demonstrated in vitro that AQP1 and AQP5 in the porcine uterus are regulated by steroid hormones (P4, E2), arachidonic acid (AA), forskolin (FSK) and cAMP during the estrous cycle. However, the potential of the porcine separated uterine tissues, the endometrium and myometrium, to express these AQPs remains unknown. Thus, in this study, the responses of AQP1 and AQP5 to P4, E2 oxytocin (OT), AA, FSK and cAMP in the porcine endometrium and myometrium were examined during the mid-luteal phase of the estrous cycle and luteolysis. Real-time PCR and western blot analysis. Progesterone up-regulated the expression of AQP1/AQP5 mRNAs and proteins in the endometrium and myometrium, especially during luteolysis. Similarly, E2 also stimulated the expression of both AQPs, but only in the endometrium. AA led to the upregulation of AQP1/AQP5 in the endometrium during luteolysis. In turn, OT increased the expression of AQP1/AQP5 mRNAs and proteins in the myometrium during mid-luteal phase. Moreover, a stimulatory effect of forskolin and cAMP on the expression of AQP1/AQP5 mRNAs and proteins in the endometrium and myometrium dominated during luteolysis, but during the mid-luteal phase their influence on the expression of these AQPs was differentiated depending on the type of tissue and the incubation duration. These results seem to indicate that uterine tissues; endometrium and myometrium, exhibit their own AQP expression profiles in response to examined factors. Moreover, the responses of AQP1/AQP5 at mRNA and protein levels to the studied factors in the endometrium and myometrium are more pronounced during luteolysis. This suggests that the above effects of the studied factors are connected with morphological and physiological changes taking place in the pig uterus during the estrous cycle.

  14. Regression calibration with heteroscedastic error variance.

    PubMed

    Spiegelman, Donna; Logan, Roger; Grove, Douglas

    2011-01-01

    The problem of covariate measurement error with heteroscedastic measurement error variance is considered. Standard regression calibration assumes that the measurement error has a homoscedastic measurement error variance. An estimator is proposed to correct regression coefficients for covariate measurement error with heteroscedastic variance. Point and interval estimates are derived. Validation data containing the gold standard must be available. This estimator is a closed-form correction of the uncorrected primary regression coefficients, which may be of logistic or Cox proportional hazards model form, and is closely related to the version of regression calibration developed by Rosner et al. (1990). The primary regression model can include multiple covariates measured without error. The use of these estimators is illustrated in two data sets, one taken from occupational epidemiology (the ACE study) and one taken from nutritional epidemiology (the Nurses' Health Study). In both cases, although there was evidence of moderate heteroscedasticity, there was little difference in estimation or inference using this new procedure compared to standard regression calibration. It is shown theoretically that unless the relative risk is large or measurement error severe, standard regression calibration approximations will typically be adequate, even with moderate heteroscedasticity in the measurement error model variance. In a detailed simulation study, standard regression calibration performed either as well as or better than the new estimator. When the disease is rare and the errors normally distributed, or when measurement error is moderate, standard regression calibration remains the method of choice.

  15. [From clinical judgment to linear regression model.

    PubMed

    Palacios-Cruz, Lino; Pérez, Marcela; Rivas-Ruiz, Rodolfo; Talavera, Juan O

    2013-01-01

    When we think about mathematical models, such as linear regression model, we think that these terms are only used by those engaged in research, a notion that is far from the truth. Legendre described the first mathematical model in 1805, and Galton introduced the formal term in 1886. Linear regression is one of the most commonly used regression models in clinical practice. It is useful to predict or show the relationship between two or more variables as long as the dependent variable is quantitative and has normal distribution. Stated in another way, the regression is used to predict a measure based on the knowledge of at least one other variable. Linear regression has as it's first objective to determine the slope or inclination of the regression line: Y = a + bx, where "a" is the intercept or regression constant and it is equivalent to "Y" value when "X" equals 0 and "b" (also called slope) indicates the increase or decrease that occurs when the variable "x" increases or decreases in one unit. In the regression line, "b" is called regression coefficient. The coefficient of determination (R(2)) indicates the importance of independent variables in the outcome.

  16. Process modeling with the regression network.

    PubMed

    van der Walt, T; Barnard, E; van Deventer, J

    1995-01-01

    A new connectionist network topology called the regression network is proposed. The structural and underlying mathematical features of the regression network are investigated. Emphasis is placed on the intricacies of the optimization process for the regression network and some measures to alleviate these difficulties of optimization are proposed and investigated. The ability of the regression network algorithm to perform either nonparametric or parametric optimization, as well as a combination of both, is also highlighted. It is further shown how the regression network can be used to model systems which are poorly understood on the basis of sparse data. A semi-empirical regression network model is developed for a metallurgical processing operation (a hydrocyclone classifier) by building mechanistic knowledge into the connectionist structure of the regression network model. Poorly understood aspects of the process are provided for by use of nonparametric regions within the structure of the semi-empirical connectionist model. The performance of the regression network model is compared to the corresponding generalization performance results obtained by some other nonparametric regression techniques.

  17. Quantile regression applied to spectral distance decay

    USGS Publications Warehouse

    Rocchini, D.; Cade, B.S.

    2008-01-01

    Remotely sensed imagery has long been recognized as a powerful support for characterizing and estimating biodiversity. Spectral distance among sites has proven to be a powerful approach for detecting species composition variability. Regression analysis of species similarity versus spectral distance allows us to quantitatively estimate the amount of turnover in species composition with respect to spectral and ecological variability. In classical regression analysis, the residual sum of squares is minimized for the mean of the dependent variable distribution. However, many ecological data sets are characterized by a high number of zeroes that add noise to the regression model. Quantile regressions can be used to evaluate trend in the upper quantiles rather than a mean trend across the whole distribution of the dependent variable. In this letter, we used ordinary least squares (OLS) and quantile regressions to estimate the decay of species similarity versus spectral distance. The achieved decay rates were statistically nonzero (p < 0.01), considering both OLS and quantile regressions. Nonetheless, the OLS regression estimate of the mean decay rate was only half the decay rate indicated by the upper quantiles. Moreover, the intercept value, representing the similarity reached when the spectral distance approaches zero, was very low compared with the intercepts of the upper quantiles, which detected high species similarity when habitats are more similar. In this letter, we demonstrated the power of using quantile regressions applied to spectral distance decay to reveal species diversity patterns otherwise lost or underestimated by OLS regression. ?? 2008 IEEE.

  18. Geodesic least squares regression on information manifolds

    SciTech Connect

    Verdoolaege, Geert

    2014-12-05

    We present a novel regression method targeted at situations with significant uncertainty on both the dependent and independent variables or with non-Gaussian distribution models. Unlike the classic regression model, the conditional distribution of the response variable suggested by the data need not be the same as the modeled distribution. Instead they are matched by minimizing the Rao geodesic distance between them. This yields a more flexible regression method that is less constrained by the assumptions imposed through the regression model. As an example, we demonstrate the improved resistance of our method against some flawed model assumptions and we apply this to scaling laws in magnetic confinement fusion.

  19. Normalization Ridge Regression in Practice I: Comparisons Between Ordinary Least Squares, Ridge Regression and Normalization Ridge Regression.

    ERIC Educational Resources Information Center

    Bulcock, J. W.

    The problem of model estimation when the data are collinear was examined. Though the ridge regression (RR) outperforms ordinary least squares (OLS) regression in the presence of acute multicollinearity, it is not a problem free technique for reducing the variance of the estimates. It is a stochastic procedure when it should be nonstochastic and it…

  20. Effects of LPA2R, LPA3R, or EP4R agonists on luteal or endometrial function in vivo or in vitro and sirtuin or EP1R, EP2R, EP3R or EP4R agonists on endometrial secretion of PGE and PGF2αin vitro.

    PubMed

    LaPorte, Magen E; Weems, Yoshie S; Arreguin-Arevalo, Alejandro; Nett, Terry M; Tsutahara, Nicole; Sy, Tracy; Haberman, Jade; Chon, Michel; Randel, Ronald D; Weems, Charles W

    2017-06-01

    In previous work, an EP2 prostanoid receptor (EP2R) agonist in vivo increased mRNA expression of luteal LH receptors (LHR), unoccupied and occupied luteal; LHR, and circulating progesterone, while an EP3R or FPR agonist decreased; mRNA expression of luteal LHR, unoccupied and occupied luteal LHR, and; circulating progesterone. An EP4R and lysophosphatidic acid (LPA) LPA2R and LPA3R agonists were reported to inhibit luteal function and sirtuins have been proposed to increase prostaglandin synthesis. The objectives were to determine; whether an EP4R, LPA2R, or LPA3R agonist affect ovine luteal function in vivo or; in vitro. In addition, whether sirtuin (SIRT)-1, 2, or 3; LPA2R or LPA3R; or EP1R, EP2R, EP3R, or EP4R agonists affect caruncular endometrial PGF2α or PGE (PGE1+PGE2) secretion in vitro. Day-10 nonpregnant ewes received a single injection of Vehicle (N = 5); an LPA2R (N = 5); LPA3R (N = 6); or EP4R (N = 5) agonist given into the interstitial tissue of the ovarian vascular pedicle adjacent to the luteal-containing ovary to determine effects on circulating progesterone, mRNA expression of luteal LHR, and luteal unoccupied and occupied LHR. In addition, agonists for LPA2R, LPA3R, EP1R, EP2R, EP3R, or EP4R or SIRT-1, SIRT-2, or SIRT-3 activators were incubated with caruncular endometrial slices in vitro to determine their effect on caruncular endometrial PGF2α, or PGE secretion. LPA2R, LPA3R, or an EP4R agonist in vivo did not affect (P ≥ 0.05) luteal weight, circulating progesterone, or occupied luteal LHR. However, an LPA2R or EP4R agonist, but; not LPA3R agonist, in vivo increased (P ≤ 0.05) mRNA expression of luteal LHR. An; LPA2R, LPA3R, or EP4R agonist increased (P ≤ 0.05) luteal unoccupied LHR, but; not occupied LHR. An LPA2R, LPA3R, or an EP4R agonist did not affect (P ≥ 0.05); luteal progesterone secretion in vitro. An LPA2R or LPA3R agonist did not affect (P ≥ 0.05) luteal PGF2α, or PGE secretion in

  1. Regression Analysis and the Sociological Imagination

    ERIC Educational Resources Information Center

    De Maio, Fernando

    2014-01-01

    Regression analysis is an important aspect of most introductory statistics courses in sociology but is often presented in contexts divorced from the central concerns that bring students into the discipline. Consequently, we present five lesson ideas that emerge from a regression analysis of income inequality and mortality in the USA and Canada.

  2. Developmental regression in autism spectrum disorders.

    PubMed

    Rogers, Sally J

    2004-01-01

    The occurrence of developmental regression in autism is one of the more puzzling features of this disorder. Although several studies have documented the validity of parental reports of regression using home videos, accumulating data suggest that most children who demonstrate regression also demonstrated previous, subtle, developmental differences. Counter to clinical intuition, the earlier development of social, language, and attachment behaviors followed by regression does not seem to support later recovery of skills or better developmental outcomes compared to children who never had speech or typical social responsivity. In fact, this regressive group may have somewhat greater developmental impairment than the nonregressive group, though the two groups do not appear to present different behavioral phenotypes. Although autism is not the only condition in which regression occurs, it appears to be the most frequent condition. Other disorders that demonstrate an early regression with no known etiology include total blindness from birth and childhood disintegrative disorder, both of which demonstrate behavioral relations to autism. In addition, two biological conditions with known etiologies also involve regression with some behaviors resembling autism behavioral phenotype: Rett syndrome (a genetic disorder; see Glaze, this issue) and Landau-Kleffner syndrome (see McVicar and Shinnar, this issue), which involves a seizure disorder.

  3. Three-Dimensional Modeling in Linear Regression.

    ERIC Educational Resources Information Center

    Herman, James D.

    Linear regression examines the relationship between one or more independent (predictor) variables and a dependent variable. By using a particular formula, regression determines the weights needed to minimize the error term for a given set of predictors. With one predictor variable, the relationship between the predictor and the dependent variable…

  4. Principles of Quantile Regression and an Application

    ERIC Educational Resources Information Center

    Chen, Fang; Chalhoub-Deville, Micheline

    2014-01-01

    Newer statistical procedures are typically introduced to help address the limitations of those already in practice or to deal with emerging research needs. Quantile regression (QR) is introduced in this paper as a relatively new methodology, which is intended to overcome some of the limitations of least squares mean regression (LMR). QR is more…

  5. Common pitfalls in statistical analysis: Logistic regression

    PubMed Central

    Ranganathan, Priya; Pramesh, C. S.; Aggarwal, Rakesh

    2017-01-01

    Logistic regression analysis is a statistical technique to evaluate the relationship between various predictor variables (either categorical or continuous) and an outcome which is binary (dichotomous). In this article, we discuss logistic regression analysis and the limitations of this technique. PMID:28828311

  6. Incremental Net Effects in Multiple Regression

    ERIC Educational Resources Information Center

    Lipovetsky, Stan; Conklin, Michael

    2005-01-01

    A regular problem in regression analysis is estimating the comparative importance of the predictors in the model. This work considers the 'net effects', or shares of the predictors in the coefficient of the multiple determination, which is a widely used characteristic of the quality of a regression model. Estimation of the net effects can be a…

  7. Suppression Situations in Multiple Linear Regression

    ERIC Educational Resources Information Center

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  8. Suppression Situations in Multiple Linear Regression

    ERIC Educational Resources Information Center

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  9. Stepwise versus Hierarchical Regression: Pros and Cons

    ERIC Educational Resources Information Center

    Lewis, Mitzi

    2007-01-01

    Multiple regression is commonly used in social and behavioral data analysis. In multiple regression contexts, researchers are very often interested in determining the "best" predictors in the analysis. This focus may stem from a need to identify those predictors that are supportive of theory. Alternatively, the researcher may simply be interested…

  10. Regression Analysis: Legal Applications in Institutional Research

    ERIC Educational Resources Information Center

    Frizell, Julie A.; Shippen, Benjamin S., Jr.; Luna, Andrew L.

    2008-01-01

    This article reviews multiple regression analysis, describes how its results should be interpreted, and instructs institutional researchers on how to conduct such analyses using an example focused on faculty pay equity between men and women. The use of multiple regression analysis will be presented as a method with which to compare salaries of…

  11. Deriving the Regression Equation without Using Calculus

    ERIC Educational Resources Information Center

    Gordon, Sheldon P.; Gordon, Florence S.

    2004-01-01

    Probably the one "new" mathematical topic that is most responsible for modernizing courses in college algebra and precalculus over the last few years is the idea of fitting a function to a set of data in the sense of a least squares fit. Whether it be simple linear regression or nonlinear regression, this topic opens the door to applying the…

  12. Regression Analysis and the Sociological Imagination

    ERIC Educational Resources Information Center

    De Maio, Fernando

    2014-01-01

    Regression analysis is an important aspect of most introductory statistics courses in sociology but is often presented in contexts divorced from the central concerns that bring students into the discipline. Consequently, we present five lesson ideas that emerge from a regression analysis of income inequality and mortality in the USA and Canada.

  13. Dealing with Outliers: Robust, Resistant Regression

    ERIC Educational Resources Information Center

    Glasser, Leslie

    2007-01-01

    Least-squares linear regression is the best of statistics and it is the worst of statistics. The reasons for this paradoxical claim, arising from possible inapplicability of the method and the excessive influence of "outliers", are discussed and substitute regression methods based on median selection, which is both robust and resistant, are…

  14. Regression Analysis: Legal Applications in Institutional Research

    ERIC Educational Resources Information Center

    Frizell, Julie A.; Shippen, Benjamin S., Jr.; Luna, Andrew L.

    2008-01-01

    This article reviews multiple regression analysis, describes how its results should be interpreted, and instructs institutional researchers on how to conduct such analyses using an example focused on faculty pay equity between men and women. The use of multiple regression analysis will be presented as a method with which to compare salaries of…

  15. A Practical Guide to Regression Discontinuity

    ERIC Educational Resources Information Center

    Jacob, Robin; Zhu, Pei; Somers, Marie-Andrée; Bloom, Howard

    2012-01-01

    Regression discontinuity (RD) analysis is a rigorous nonexperimental approach that can be used to estimate program impacts in situations in which candidates are selected for treatment based on whether their value for a numeric rating exceeds a designated threshold or cut-point. Over the last two decades, the regression discontinuity approach has…

  16. Implementing Variable Selection Techniques in Regression.

    ERIC Educational Resources Information Center

    Thayer, Jerome D.

    Variable selection techniques in stepwise regression analysis are discussed. In stepwise regression, variables are added or deleted from a model in sequence to produce a final "good" or "best" predictive model. Stepwise computer programs are discussed and four different variable selection strategies are described. These…

  17. Understanding logistic regression analysis through example.

    PubMed

    Ely, J W; Dawson, J D; Mehr, D R; Burns, T L

    1996-02-01

    Logistic regression is a valuable statistical tool that is often used in primary care research. When researchers explore the association between a possible risk factor and a disease, they attempt to control the effects of extraneous factors (confounders) that can obscure the true association. Using logistic regression, researchers can simultaneously control for the effects of multiple confounders. When investigators use logistic regression, they make subjective decisions about which factors to include in the analysis and in the final predictive model. Critical readers must understand basic concepts of logistic regression and potential problems with its use before they can accurately interpret study results. This article uses a familiar example to explain the principles of logistic regression to make it understandable to nonstatisticians.

  18. Should metacognition be measured by logistic regression?

    PubMed

    Rausch, Manuel; Zehetleitner, Michael

    2017-03-01

    Are logistic regression slopes suitable to quantify metacognitive sensitivity, i.e. the efficiency with which subjective reports differentiate between correct and incorrect task responses? We analytically show that logistic regression slopes are independent from rating criteria in one specific model of metacognition, which assumes (i) that rating decisions are based on sensory evidence generated independently of the sensory evidence used for primary task responses and (ii) that the distributions of evidence are logistic. Given a hierarchical model of metacognition, logistic regression slopes depend on rating criteria. According to all considered models, regression slopes depend on the primary task criterion. A reanalysis of previous data revealed that massive numbers of trials are required to distinguish between hierarchical and independent models with tolerable accuracy. It is argued that researchers who wish to use logistic regression as measure of metacognitive sensitivity need to control the primary task criterion and rating criteria.

  19. Atherosclerotic plaque regression: fact or fiction?

    PubMed

    Shanmugam, Nesan; Román-Rego, Ana; Ong, Peter; Kaski, Juan Carlos

    2010-08-01

    Coronary artery disease is the major cause of death in the western world. The formation and rapid progression of atheromatous plaques can lead to serious cardiovascular events in patients with atherosclerosis. The better understanding, in recent years, of the mechanisms leading to atheromatous plaque growth and disruption and the availability of powerful HMG CoA-reductase inhibitors (statins) has permitted the consideration of plaque regression as a realistic therapeutic goal. This article reviews the existing evidence underpinning current therapeutic strategies aimed at achieving atherosclerotic plaque regression. In this review we also discuss imaging modalities for the assessment of plaque regression, predictors of regression and whether plaque regression is associated with a survival benefit.

  20. Extracting regression rules from neural networks.

    PubMed

    Saito, Kazumi; Nakano, Ryohei

    2002-12-01

    This paper proposes a new framework and method for extracting regression rules from neural networks trained with multivariate data containing both nominal and numeric variables. Each regression rule is expressed as a pair of a logical formula on the conditional part over nominal variables and a polynomial equation on the action part over numeric variables. The proposed extraction method first generates one such regression rule for each training sample, then utilizes the kappa-means algorithm to generate a much smaller set of rules having more general conditions, where the number of distinct polynomial equations is determined through cross-validation. Finally, this method invokes decision-tree induction to form logical formulae of nominal conditions as conditional parts of final regression rules. Experiments using four data sets show that our method works well in extracting quite accurate and interesting regression rules.

  1. Substituted trans-stilbenes, including analogues of the natural product resveratrol, inhibit the human tumor necrosis factor alpha-induced activation of transcription factor nuclear factor kappaB.

    PubMed

    Heynekamp, Justin J; Weber, Waylon M; Hunsaker, Lucy A; Gonzales, Amanda M; Orlando, Robert A; Deck, Lorraine M; Jagt, David L Vander

    2006-11-30

    The transcription factor nuclear factor kappaB (NF-kappaB), which regulates expression of numerous antiinflammatory genes as well as genes that promote development of the prosurvival, antiapoptotic state is up-regulated in many cancer cells. The natural product resveratrol, a polyphenolic trans-stilbene, has numerous biological activities and is a known inhibitor of activation of NF-kappaB, which may account for some of its biological activities. Resveratrol exhibits activity against a wide variety of cancer cells and has demonstrated activity as a cancer chemopreventive against all stages, i.e., initiation, promotion, and progression. The biological activities of resveratrol are often ascribed to its antioxidant activity. Both antioxidant activity and biological activities of analogues of resveratrol depend upon the number and location of the hydroxy groups. In the present study, phenolic analogues of resveratrol and a series of substituted trans-stilbenes without hydroxy groups were compared with resveratrol for their abilities to inhibit the human tumor necrosis factor alpha-induced (TNF-alpha) activation of NF-kappaB, using the Panomics NF-kappaB stable reporter cell line 293/NF-kappaB-luc. A series of 75 compounds was screened to identify substituted trans-stilbenes that were more active than resveratrol. Dose-response studies of the most active compounds were carried out to obtain IC50 values. Numerous compounds were identified that were more active than resveratrol, including compounds that were devoid of hydroxy groups and were 100-fold more potent than resveratrol. The substituted trans-stilbenes that were potent inhibitors of the activation of NFkappaB generally did not exhibit antioxidant activity. The results from screening were confirmed using BV-2 microglial cells where resveratrol and analogues were shown to inhibit LPS-induced COX-2 expression.

  2. Almost efficient estimation of relative risk regression

    PubMed Central

    Fitzmaurice, Garrett M.; Lipsitz, Stuart R.; Arriaga, Alex; Sinha, Debajyoti; Greenberg, Caprice; Gawande, Atul A.

    2014-01-01

    Relative risks (RRs) are often considered the preferred measures of association in prospective studies, especially when the binary outcome of interest is common. In particular, many researchers regard RRs to be more intuitively interpretable than odds ratios. Although RR regression is a special case of generalized linear models, specifically with a log link function for the binomial (or Bernoulli) outcome, the resulting log-binomial regression does not respect the natural parameter constraints. Because log-binomial regression does not ensure that predicted probabilities are mapped to the [0,1] range, maximum likelihood (ML) estimation is often subject to numerical instability that leads to convergence problems. To circumvent these problems, a number of alternative approaches for estimating RR regression parameters have been proposed. One approach that has been widely studied is the use of Poisson regression estimating equations. The estimating equations for Poisson regression yield consistent, albeit inefficient, estimators of the RR regression parameters. We consider the relative efficiency of the Poisson regression estimator and develop an alternative, almost efficient estimator for the RR regression parameters. The proposed method uses near-optimal weights based on a Maclaurin series (Taylor series expanded around zero) approximation to the true Bernoulli or binomial weight function. This yields an almost efficient estimator while avoiding convergence problems. We examine the asymptotic relative efficiency of the proposed estimator for an increase in the number of terms in the series. Using simulations, we demonstrate the potential for convergence problems with standard ML estimation of the log-binomial regression model and illustrate how this is overcome using the proposed estimator. We apply the proposed estimator to a study of predictors of pre-operative use of beta blockers among patients undergoing colorectal surgery after diagnosis of colon cancer. PMID

  3. Effect of GnRH and hCG on progesterone concentration and ovarian and luteal blood flow in diestrous mares.

    PubMed

    Brito, L F C; Baldrighi, J M; Wolf, C A; Ginther, O J

    2017-01-01

    The objective of the present study was to investigate the effect of reproductive hormones (GnRH, hCG, LH and progesterone) on the regulation of corpus luteum (CL) and ovarian blood flow. Diestrous mares received a single treatment of saline, 100μg gonadorelin (GnRH), or 1500IU hCG 10days after ovulation. Plasma LH and progesterone concentrations, resistance index (RI) for ovarian artery blood-flow, and percentage of corpus luteum (CL) with color-Doppler signals of blood flow were determined immediately before treatment (hour 0) and at hours 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 6. In the GnRH group, LH increased (P<0.0001) between hours 0 and 0.25 and then progressively decreased; concentration of LH was not affected in the saline and hCG groups. Progesterone concentration was not different among groups. In the GnRH group, RI tended (P<0.07) to decrease between hours 0 and 1.5 and increased (P<0.01) between hours 1.5 and 4. In the hCG group, two transient RI decreases (P<0.05) occurred before hour 2. The percentage change from hour 0 in the percentage of CL with blood-flow signals was greater at hour 0.5 in the GnRH group than in the saline group and was intermediate in the hCG group. The similarity among groups in progesterone concentration indicated that changes in progesterone were not involved in the GnRH and hCG stimulation of ovarian vascular perfusion. Effects of treatment might have been mediated through LH; however, since hCG biological activity is primarily LH-like, the differences in timing and degree of ovarian and luteal blood flow changes after GnRH or hCG administration in the present study suggest that GnRH might have a direct effect on ovarian blood vessels and vascular control. Copyright © 2016. Published by Elsevier B.V.

  4. Ovulatory response and luteal function after eCG administration at the end of a progesterone and estradiol' based treatment in postpartum anestrous beef cattle.

    PubMed

    Núñez-Olivera, R; de Castro, T; García-Pintos, C; Bó, G; Piaggio, J; Menchaca, A

    2014-05-01

    The objective of this study was to evaluate the effect of equine chorionic gonadotropin (eCG) administration associated to fixed-time AI (FTAI) on follicular dynamics, ovulation, corpus luteum (CL) development and serum progesterone concentrations. Multiparous suckled Hereford cows (n=46) in anestrus with 60-75 days postpartum were used. Females received an intravaginal device containing 0.5g of progesterone during 8 days and 2mg of estradiol benzoate i.m. at device insertion. At device removal 500μg of cloprostenol and 0.5mg of estradiol cypionate were administered i.m., and FTAI was performed 52-56h later. Cows were divided into two experimental groups to receive 400IU of eCG i.m. at device removal (n=23), while control group did not receive eCG (n=23). Daily ovarian ultrasonography (7.5MHz transducer) and progesterone concentrations determined by RIA were assayed from device removal until 30 or 14 days after FTAI, respectively. Treatment with eCG increased ovulation rate [65.2% (15/23) vs. 30.4% (7/23); P=0.018], ovulatory follicle diameter (14.5±0.4 vs. 13.1±0.7mm, mean±SEM; P=0.081), CL area from 6 to 14 days after FTAI (344.3±25.1 vs. 274.2±23.9mm(2); P=0.045) and mean serum progesterone concentrations from FTAI to 14 days later (3.0±0.2 vs. 1.8±0.2ng/ml; P=0.001), in comparison with control cows. In conclusion, the addition of eCG to a progesterone and estradiol' based treatment for FTAI improves ovulation rate and luteal function in anestrous cows. These findings have implications in order to increase pregnancy rates in FTAI treatments in Bos taurus beef cattle. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Interferon-alpha induced Raynaud's syndrome.

    PubMed

    Kruit, W H; Eggermont, A M; Stoter, G

    2000-11-01

    The cytokine interferon-alpha (IFN-alpha) is increasingly prescribed for a number of indications, especially viral hepatitis and several malignancies. Two patients are described who developed Raynaud's syndrome during treatment with IFN-alpha as adjuvant therapy for high-risk melanoma. With a review of the available literature the symptomatology, possible pathophysiologic mechanisms and treatment options are discussed.

  6. Prostaglandin F2a activates stress response signaling and induces expression of activating transcription factor 3 (ATF3) in bovine large luteal cells

    USDA-ARS?s Scientific Manuscript database

    The pulsatile uterine secretion of prostaglandin F2 alpha (PGF) triggers the regression of the corpus luteum (CL). Recent studies have explored global changes in gene expression in response to PGF that may contribute to structural and functional regression of the CL. Activating transcription facto...

  7. Investigating bias in squared regression structure coefficients.

    PubMed

    Nimon, Kim F; Zientek, Linda R; Thompson, Bruce

    2015-01-01

    The importance of structure coefficients and analogs of regression weights for analysis within the general linear model (GLM) has been well-documented. The purpose of this study was to investigate bias in squared structure coefficients in the context of multiple regression and to determine if a formula that had been shown to correct for bias in squared Pearson correlation coefficients and coefficients of determination could be used to correct for bias in squared regression structure coefficients. Using data from a Monte Carlo simulation, this study found that squared regression structure coefficients corrected with Pratt's formula produced less biased estimates and might be more accurate and stable estimates of population squared regression structure coefficients than estimates with no such corrections. While our findings are in line with prior literature that identified multicollinearity as a predictor of bias in squared regression structure coefficients but not coefficients of determination, the findings from this study are unique in that the level of predictive power, number of predictors, and sample size were also observed to contribute bias in squared regression structure coefficients.

  8. Regression modeling of ground-water flow

    USGS Publications Warehouse

    Cooley, R.L.; Naff, R.L.

    1985-01-01

    Nonlinear multiple regression methods are developed to model and analyze groundwater flow systems. Complete descriptions of regression methodology as applied to groundwater flow models allow scientists and engineers engaged in flow modeling to apply the methods to a wide range of problems. Organization of the text proceeds from an introduction that discusses the general topic of groundwater flow modeling, to a review of basic statistics necessary to properly apply regression techniques, and then to the main topic: exposition and use of linear and nonlinear regression to model groundwater flow. Statistical procedures are given to analyze and use the regression models. A number of exercises and answers are included to exercise the student on nearly all the methods that are presented for modeling and statistical analysis. Three computer programs implement the more complex methods. These three are a general two-dimensional, steady-state regression model for flow in an anisotropic, heterogeneous porous medium, a program to calculate a measure of model nonlinearity with respect to the regression parameters, and a program to analyze model errors in computed dependent variables such as hydraulic head. (USGS)

  9. Investigating bias in squared regression structure coefficients

    PubMed Central

    Nimon, Kim F.; Zientek, Linda R.; Thompson, Bruce

    2015-01-01

    The importance of structure coefficients and analogs of regression weights for analysis within the general linear model (GLM) has been well-documented. The purpose of this study was to investigate bias in squared structure coefficients in the context of multiple regression and to determine if a formula that had been shown to correct for bias in squared Pearson correlation coefficients and coefficients of determination could be used to correct for bias in squared regression structure coefficients. Using data from a Monte Carlo simulation, this study found that squared regression structure coefficients corrected with Pratt's formula produced less biased estimates and might be more accurate and stable estimates of population squared regression structure coefficients than estimates with no such corrections. While our findings are in line with prior literature that identified multicollinearity as a predictor of bias in squared regression structure coefficients but not coefficients of determination, the findings from this study are unique in that the level of predictive power, number of predictors, and sample size were also observed to contribute bias in squared regression structure coefficients. PMID:26217273

  10. The orphan nuclear receptor SF-1 is involved in the effect of PCBs, DDT, and DDE on the secretion of steroid hormones and oxytocin from bovine luteal cells during the estrous cycle in vitro.

    PubMed

    Mlynarczuk, J; Wrobel, M H; Kotwica, J

    2014-04-15

    The orphan receptor steroidogenic factor-1 (SF-1) is involved in the regulation of ovarian steroidogenesis in cows. It is hypothesized that estrogen-like chlorinated compounds might affect SF-1, and thus impair the function of the ovary. Bovine luteal cells from the estrous cycle (Days: 1-5, 6-10, 11-15, and 16-19) were treated for 50 hours with DDT, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethene, 3,3'4,4'-tetrachlorobiphenyl or 2'2'4,4',5,5'-hexachlorobiphenyl (each at a dose of 10 ng/mL). Luteal cells were also treated with 4-(heptyloxy)phenol (1 × 10(-7) M), an SF-1 agonist, and F0160 (1 × 10(-6) M), an SF-1 blocker, jointly or separately. The secretion of progesterone and oxytocin and the expression of oxytocin precursor (NP-I/OT) messenger RNA were increased (P < 0.05) by all studied xenobiotics and 4-(heptyloxy)phenol, although they were inhibited (P < 0.05) by F0160. However, the xenobiotics did not affect (P > 0.05) SF-1 messenger RNA expression. In summary, SF-1 is involved in the adverse effect of chlorinated xenobiotics on the regulation of the bovine CL.

  11. Relative risk regression analysis of epidemiologic data.

    PubMed

    Prentice, R L

    1985-11-01

    Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation

  12. Regression of altitude-produced cardiac hypertrophy.

    NASA Technical Reports Server (NTRS)

    Sizemore, D. A.; Mcintyre, T. W.; Van Liere, E. J.; Wilson , M. F.

    1973-01-01

    The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

  13. Semiparametric Regression in Size-Biased Sampling

    PubMed Central

    Chen, Ying Qing

    2009-01-01

    Summary Size-biased sampling arises when a positive-valued outcome variable is sampled with selection probability proportional to its size. In this article, we propose a semiparametric linear regression model to analyze size-biased outcomes. In our proposed model, the regression parameters of the covariates are of major interest, while the distribution of random errors is unspecified. Under the proposed model, we discover that the regression parameters are invariant regardless of size-biased sampling. Following this invariance property, we develop a simple estimation procedure for inferences. Our proposed methods are evaluated in simulation studies and applied to two real data analyses. PMID:19432792

  14. Regressive language in severe head injury.

    PubMed

    Thomsen, I V; Skinhoj, E

    1976-09-01

    In a follow-up study of 50 patients with severe head injuries three patients had echolalia. One patient with initially global aphasia had echolalia for some weeks when he started talking. Another patient with severe diffuse brain damage, dementia, and emotional regression had echolalia. The dysfunction was considered a detour performance. In the third patient echolalia and palilalia were details in a total pattern of regression lasting for months. The patient, who had extensive frontal atrophy secondary to a very severe head trauma, presented an extreme state of regression returning to a foetal-body pattern and behaving like a baby.

  15. Regression of altitude-produced cardiac hypertrophy.

    NASA Technical Reports Server (NTRS)

    Sizemore, D. A.; Mcintyre, T. W.; Van Liere, E. J.; Wilson , M. F.

    1973-01-01

    The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

  16. A comparison of regression and regression-kriging for soil characterization using remote sensing imagery

    USDA-ARS?s Scientific Manuscript database

    In precision agriculture regression has been used widely to quality the relationship between soil attributes and other environmental variables. However, spatial correlation existing in soil samples usually makes the regression model suboptimal. In this study, a regression-kriging method was attemp...

  17. Modelling of filariasis in East Java with Poisson regression and generalized Poisson regression models

    NASA Astrophysics Data System (ADS)

    Darnah

    2016-04-01

    Poisson regression has been used if the response variable is count data that based on the Poisson distribution. The Poisson distribution assumed equal dispersion. In fact, a situation where count data are over dispersion or under dispersion so that Poisson regression inappropriate because it may underestimate the standard errors and overstate the significance of the regression parameters, and consequently, giving misleading inference about the regression parameters. This paper suggests the generalized Poisson regression model to handling over dispersion and under dispersion on the Poisson regression model. The Poisson regression model and generalized Poisson regression model will be applied the number of filariasis cases in East Java. Based regression Poisson model the factors influence of filariasis are the percentage of families who don't behave clean and healthy living and the percentage of families who don't have a healthy house. The Poisson regression model occurs over dispersion so that we using generalized Poisson regression. The best generalized Poisson regression model showing the factor influence of filariasis is percentage of families who don't have healthy house. Interpretation of result the model is each additional 1 percentage of families who don't have healthy house will add 1 people filariasis patient.

  18. TWSVR: Regression via Twin Support Vector Machine.

    PubMed

    Khemchandani, Reshma; Goyal, Keshav; Chandra, Suresh

    2016-02-01

    Taking motivation from Twin Support Vector Machine (TWSVM) formulation, Peng (2010) attempted to propose Twin Support Vector Regression (TSVR) where the regressor is obtained via solving a pair of quadratic programming problems (QPPs). In this paper we argue that TSVR formulation is not in the true spirit of TWSVM. Further, taking motivation from Bi and Bennett (2003), we propose an alternative approach to find a formulation for Twin Support Vector Regression (TWSVR) which is in the true spirit of TWSVM. We show that our proposed TWSVR can be derived from TWSVM for an appropriately constructed classification problem. To check the efficacy of our proposed TWSVR we compare its performance with TSVR and classical Support Vector Regression(SVR) on various regression datasets.

  19. Bayesian Comparison of Two Regression Lines.

    ERIC Educational Resources Information Center

    Tsutakawa, Robert K.

    1978-01-01

    A Bayesian solution is presented for the Johnson-Neyman problem (whether or not the distance between two regression lines is statistically significant over a finite interval of the independent variable). (Author/CTM)

  20. Spontaneous Regression of an Incidental Spinal Meningioma.

    PubMed

    Yilmaz, Ali; Kizilay, Zahir; Sair, Ahmet; Avcil, Mucahit; Ozkul, Ayca

    2016-03-15

    The regression of meningioma has been reported in literature before. In spite of the fact that the regression may be involved by hemorrhage, calcification or some drugs withdrawal, it is rarely observed spontaneously. We report a 17 year old man with a cervical meningioma which was incidentally detected. In his cervical MRI an extradural, cranio-caudal contrast enchanced lesion at C2-C3 levels of the cervical spinal cord was detected. Despite the slight compression towards the spinal cord, he had no symptoms and refused any kind of surgical approach. The meningioma was followed by control MRI and it spontaneously regressed within six months. There were no signs of hemorrhage or calcification. Although it is a rare condition, the clinicians should consider that meningiomas especially incidentally diagnosed may be regressed spontaneously.

  1. An introduction to multilevel regression models.

    PubMed

    Austin, P C; Goel, V; van Walraven, C

    2001-01-01

    Data in health research are frequently structured hierarchically. For example, data may consist of patients nested within physicians, who in turn may be nested in hospitals or geographic regions. Fitting regression models that ignore the hierarchical structure of the data can lead to false inferences being drawn from the data. Implementing a statistical analysis that takes into account the hierarchical structure of the data requires special methodologies. In this paper, we introduce the concept of hierarchically structured data, and present an introduction to hierarchical regression models. We then compare the performance of a traditional regression model with that of a hierarchical regression model on a dataset relating test utilization at the annual health exam with patient and physician characteristics. In comparing the resultant models, we see that false inferences can be drawn by ignoring the structure of the data.

  2. Multiple Instance Regression with Structured Data

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Lane, Terran; Roper, Alex

    2008-01-01

    This slide presentation reviews the use of multiple instance regression with structured data from multiple and related data sets. It applies the concept to a practical problem, that of estimating crop yield using remote sensed country wide weekly observations.

  3. Weighted regression analysis and interval estimators

    Treesearch

    Donald W. Seegrist

    1974-01-01

    A method for deriving the weighted least squares estimators for the parameters of a multiple regression model. Confidence intervals for expected values, and prediction intervals for the means of future samples are given.

  4. A new bivariate negative binomial regression model

    NASA Astrophysics Data System (ADS)

    Faroughi, Pouya; Ismail, Noriszura

    2014-12-01

    This paper introduces a new form of bivariate negative binomial (BNB-1) regression which can be fitted to bivariate and correlated count data with covariates. The BNB regression discussed in this study can be fitted to bivariate and overdispersed count data with positive, zero or negative correlations. The joint p.m.f. of the BNB1 distribution is derived from the product of two negative binomial marginals with a multiplicative factor parameter. Several testing methods were used to check overdispersion and goodness-of-fit of the model. Application of BNB-1 regression is illustrated on Malaysian motor insurance dataset. The results indicated that BNB-1 regression has better fit than bivariate Poisson and BNB-2 models with regards to Akaike information criterion.

  5. Some Simple Computational Formulas for Multiple Regression

    ERIC Educational Resources Information Center

    Aiken, Lewis R., Jr.

    1974-01-01

    Short-cut formulas are presented for direct computation of the beta weights, the standard errors of the beta weights, and the multiple correlation coefficient for multiple regression problems involving three independent variables and one dependent variable. (Author)

  6. Discriminative Elastic-Net Regularized Linear Regression.

    PubMed

    Zhang, Zheng; Lai, Zhihui; Xu, Yong; Shao, Ling; Wu, Jian; Xie, Guo-Sen

    2017-03-01

    In this paper, we aim at learning compact and discriminative linear regression models. Linear regression has been widely used in different problems. However, most of the existing linear regression methods exploit the conventional zero-one matrix as the regression targets, which greatly narrows the flexibility of the regression model. Another major limitation of these methods is that the learned projection matrix fails to precisely project the image features to the target space due to their weak discriminative capability. To this end, we present an elastic-net regularized linear regression (ENLR) framework, and develop two robust linear regression models which possess the following special characteristics. First, our methods exploit two particular strategies to enlarge the margins of different classes by relaxing the strict binary targets into a more feasible variable matrix. Second, a robust elastic-net regularization of singular values is introduced to enhance the compactness and effectiveness of the learned projection matrix. Third, the resulting optimization problem of ENLR has a closed-form solution in each iteration, which can be solved efficiently. Finally, rather than directly exploiting the projection matrix for recognition, our methods employ the transformed features as the new discriminate representations to make final image classification. Compared with the traditional linear regression model and some of its variants, our method is much more accurate in image classification. Extensive experiments conducted on publicly available data sets well demonstrate that the proposed framework can outperform the state-of-the-art methods. The MATLAB codes of our methods can be available at http://www.yongxu.org/lunwen.html.

  7. The Geometry of Enhancement in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2011-01-01

    In linear multiple regression, "enhancement" is said to occur when R[superscript 2] = b[prime]r greater than r[prime]r, where b is a p x 1 vector of standardized regression coefficients and r is a p x 1 vector of correlations between a criterion y and a set of standardized regressors, x. When p = 1 then b [is congruent to] r and…

  8. Marginal longitudinal semiparametric regression via penalized splines

    PubMed Central

    Kadiri, M. Al; Carroll, R.J.; Wand, M.P.

    2010-01-01

    We study the marginal longitudinal nonparametric regression problem and some of its semiparametric extensions. We point out that, while several elaborate proposals for efficient estimation have been proposed, a relative simple and straightforward one, based on penalized splines, has not. After describing our approach, we then explain how Gibbs sampling and the BUGS software can be used to achieve quick and effective implementation. Illustrations are provided for nonparametric regression and additive models. PMID:21037941

  9. Fuzzy multiple linear regression: A computational approach

    NASA Technical Reports Server (NTRS)

    Juang, C. H.; Huang, X. H.; Fleming, J. W.

    1992-01-01

    This paper presents a new computational approach for performing fuzzy regression. In contrast to Bardossy's approach, the new approach, while dealing with fuzzy variables, closely follows the conventional regression technique. In this approach, treatment of fuzzy input is more 'computational' than 'symbolic.' The following sections first outline the formulation of the new approach, then deal with the implementation and computational scheme, and this is followed by examples to illustrate the new procedure.

  10. The Geometry of Enhancement in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2011-01-01

    In linear multiple regression, "enhancement" is said to occur when R[superscript 2] = b[prime]r greater than r[prime]r, where b is a p x 1 vector of standardized regression coefficients and r is a p x 1 vector of correlations between a criterion y and a set of standardized regressors, x. When p = 1 then b [is congruent to] r and…

  11. Adaptive prior weighting in generalized regression.

    PubMed

    Held, Leonhard; Sauter, Rafael

    2017-03-01

    The prior distribution is a key ingredient in Bayesian inference. Prior information on regression coefficients may come from different sources and may or may not be in conflict with the observed data. Various methods have been proposed to quantify a potential prior-data conflict, such as Box's p-value. However, there are no clear recommendations how to react to possible prior-data conflict in generalized regression models. To address this deficiency, we propose to adaptively weight a prespecified multivariate normal prior distribution on the regression coefficients. To this end, we relate empirical Bayes estimates of prior weight to Box's p-value and propose alternative fully Bayesian approaches. Prior weighting can be done for the joint prior distribution of the regression coefficients or-under prior independence-separately for prespecified blocks of regression coefficients. We outline how the proposed methodology can be implemented using integrated nested Laplace approximations (INLA) and illustrate the applicability with a Bayesian logistic regression model for data from a cross-sectional study. We also provide a simulation study that shows excellent performance of our approach in the case of prior misspecification in terms of root mean squared error and coverage. Supplementary Materials give details on software implementation and code and another application to binary longitudinal data from a randomized clinical trial using a Bayesian generalized linear mixed model. © 2016, The International Biometric Society.

  12. [Iris movement mediates pupillary membrane regression].

    PubMed

    Morizane, Yuki

    2007-11-01

    In the course of mammalian lens development, a transient capillary meshwork called as the pupillary membrane (PM) forms. It is located in the pupil area to nourish the anterior surface of the lens, and then regresses to clear the optical path. Although the involvement of the apoptotic process has been reported in PM regression, the initiating factor remains unknown. We initially found that regression of the PM coincided with the development of iris motility, and that iris movement caused cessation and resumption of blood flow within the PM. Therefore, we investigated whether the development of the capacity of the iris to constrict and dilate can function as an essential signal that induces apoptosis in the PM. Continuous inhibition of iris movement with mydriatic agents suppressed apoptosis of the PM and resulted in the persistence of PM in rats. The distribution of apoptotic cells in the regressing PM was diffuse and showed no apparent localization. These results indicated that iris movement induced regression of the PM by changing the blood flow within it. This study suggests the importance of the physiological interactions between tissues-in this case, the iris and the PM-as a signal to advance vascular regression during organ development.

  13. Dermoscopy of fully regressive cutaneous melanoma.

    PubMed

    Bories, N; Dalle, S; Debarbieux, S; Balme, B; Ronger-Savlé, S; Thomas, L

    2008-06-01

    Metastatic melanoma of unknown origin is a difficult challenge diagnostically and therapeutically. Diagnosis of the putative primary lesion is difficult. This difficulty increases when the primary lesion has undergone complete regression. To define the dermoscopic features of fully regressed melanoma. A single-institution, register-based study of an unselected consecutive series of seven cases of metastatic melanoma in the lymph nodes with no known or visible primary lesion was carried out. Skin examination included dermoscopy; when a suspicious area was found, observed dermoscopic features were recorded and a biopsy was performed. Diagnosis of completely regressive cutaneous melanoma was based on clinical-pathological correlation according to widely accepted criteria. Seven dermoscopic features were associated with completely regressive melanoma: scar-like depigmentation (100%); pink coloration of the background (100%); linear-irregular vessels (86%); globular pattern of the vessels (43%); remnants of pigmentation (86%), either macular (43%) or with a peppering aspect (43%); and white lighter transverse bands (43%). The last feature was only observed with polarized light dermoscopy devices. Dermoscopy more accurately distinguishes the vascular, pigmentary and scarring changes of fully regressive melanoma. We believe that dermoscopy should be included in the search for a regressive primary lesion in case of metastatic melanoma of unknown origin.

  14. Multiple-Instance Regression with Structured Data

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Lane, Terran; Roper, Alex

    2008-01-01

    We present a multiple-instance regression algorithm that models internal bag structure to identify the items most relevant to the bag labels. Multiple-instance regression (MIR) operates on a set of bags with real-valued labels, each containing a set of unlabeled items, in which the relevance of each item to its bag label is unknown. The goal is to predict the labels of new bags from their contents. Unlike previous MIR methods, MI-ClusterRegress can operate on bags that are structured in that they contain items drawn from a number of distinct (but unknown) distributions. MI-ClusterRegress simultaneously learns a model of the bag's internal structure, the relevance of each item, and a regression model that accurately predicts labels for new bags. We evaluated this approach on the challenging MIR problem of crop yield prediction from remote sensing data. MI-ClusterRegress provided predictions that were more accurate than those obtained with non-multiple-instance approaches or MIR methods that do not model the bag structure.

  15. Multiple-Instance Regression with Structured Data

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Lane, Terran; Roper, Alex

    2008-01-01

    We present a multiple-instance regression algorithm that models internal bag structure to identify the items most relevant to the bag labels. Multiple-instance regression (MIR) operates on a set of bags with real-valued labels, each containing a set of unlabeled items, in which the relevance of each item to its bag label is unknown. The goal is to predict the labels of new bags from their contents. Unlike previous MIR methods, MI-ClusterRegress can operate on bags that are structured in that they contain items drawn from a number of distinct (but unknown) distributions. MI-ClusterRegress simultaneously learns a model of the bag's internal structure, the relevance of each item, and a regression model that accurately predicts labels for new bags. We evaluated this approach on the challenging MIR problem of crop yield prediction from remote sensing data. MI-ClusterRegress provided predictions that were more accurate than those obtained with non-multiple-instance approaches or MIR methods that do not model the bag structure.

  16. SM22{alpha}-induced activation of p16{sup INK4a}/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of {gamma}-radiation and doxorubicin in HepG2 cells

    SciTech Connect

    Kim, Tae Rim; Lee, Hee Min; Lee, So Yong; Kim, Eun Jin; Kim, Kug Chan; Paik, Sang Gi; Cho, Eun Wie; Kim, In Gyu

    2010-09-10

    Research highlights: {yields} SM22{alpha} overexpression in HepG2 cells leads cells to a growth arrest state, and the treatment of a subclinical dose of {gamma}-radiation or doxorubicin promotes cellular senescence. {yields} SM22{alpha} overexpression elevates p16{sup INK4a} followed by pRB activation, but there are no effects on p53/p21{sup WAF1/Cip1} pathway. {yields} SM22{alpha}-induced MT-1G activates p16{sup INK4a}/pRB pathway, which promotes cellular senescence by damaging agents. -- Abstract: Smooth muscle protein 22-alpha (SM22{alpha}) is known as a transformation- and shape change-sensitive actin cross-linking protein found in smooth muscle tissue and fibroblasts; however, its functional role remains uncertain. We reported previously that SM22{alpha} overexpression confers resistance against anti-cancer drugs or radiation via induction of metallothionein (MT) isozymes in HepG2 cells. In this study, we demonstrate that SM22{alpha} overexpression leads cells to a growth arrest state and promotes cellular senescence caused by treatment with a subclinical dose of {gamma}-radiation (0.05 and 0.1 Gy) or doxorubicin (0.01 and 0.05 {mu}g/ml), compared to control cells. Senescence growth arrest is known to be controlled by p53 phosphorylation/p21{sup WAF1/Cip1} induction or p16{sup INK4a}/retinoblastoma protein (pRB) activation. SM22{alpha} overexpression in HepG2 cells elevated p16{sup INK4a} followed by pRB activation, but did not activate the p53/p21{sup WAF1/Cip1} pathway. Moreover, MT-1G, which is induced by SM22{alpha} overexpression, was involved in the activation of the p16{sup INK4a}/pRB pathway, which led to a growth arrest state and promoted cellular senescence caused by damaging agents. Our findings provide the first demonstration that SM22{alpha} modulates cellular senescence caused by damaging agents via regulation of the p16{sup INK4a}/pRB pathway in HepG2 cells and that these effects of SM22{alpha} are partially mediated by MT-1G.

  17. Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders: a systematic review and meta-analysis

    PubMed Central

    Reynolds, Kasey A.; Omurtag, Kenan R.; Jimenez, Patricia T.; Rhee, Julie S.; Tuuli, Method G.; Jungheim, Emily S.

    2013-01-01

    STUDY QUESTION Does a luteal estradiol (LE) stimulation protocol improve outcomes in poor responders to IVF? SUMMARY ANSWER LE priming is associated with decreased cycle cancellation and increased chance of clinical pregnancy in poor responders WHAT IS KNOWN ALREADY Poor responders to IVF are one of the most challenging patient populations to treat. Many standard protocols currently exist for stimulating these patients but all have failed to improve outcomes. STUDY DESIGN, SIZE, DURATION Systematic review and meta-analysis including eight published studies comparing assisted reproduction technology (ART) outcomes in poor responders exposed to controlled ovarian hyperstimulation with and without LE priming. A search of the databases MEDLINE, EMBASE and PUBMED was carried out for studies in the English language published up to January 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Studies evaluating women defined as poor responders to ART were evaluated. These studies were identified following a systematic review of the literature and data were analyzed using the DerSimonian–Laird random effects model. The main outcomes of interest were cycle cancellation rate and clinical pregnancy. Although the definition of clinical pregnancy varied between studies, the principal definition included fetal cardiac activity as assessed by transvaginal ultrasonography after 5 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE A total of 2249 publications were identified from the initial search, and the bibliographies, abstracts and other sources yielded 11 more. After excluding duplications, 1227 studies remained and 8 ultimately met the inclusion criteria. Compared with women undergoing non-LE primed protocols (n = 621), women exposed to LE priming (n = 468) had a lower risk of cycle cancellation [relative risk (RR): 0.60, 95% confidence interval (CI): 0.45–0.78] and an improved chance of clinical pregnancy (RR: 1.33, 95% CI: 1.02–1.72). There was no significant

  18. Hyperglycemia impairs atherosclerosis regression in mice.

    PubMed

    Gaudreault, Nathalie; Kumar, Nikit; Olivas, Victor R; Eberlé, Delphine; Stephens, Kyle; Raffai, Robert L

    2013-12-01

    Diabetic patients are known to be more susceptible to atherosclerosis and its associated cardiovascular complications. However, the effects of hyperglycemia on atherosclerosis regression remain unclear. We hypothesized that hyperglycemia impairs atherosclerosis regression by modulating the biological function of lesional macrophages. HypoE (Apoe(h/h)Mx1-Cre) mice express low levels of apolipoprotein E (apoE) and develop atherosclerosis when fed a high-fat diet. Atherosclerosis regression occurs in these mice upon plasma lipid lowering induced by a change in diet and the restoration of apoE expression. We examined the morphological characteristics of regressed lesions and assessed the biological function of lesional macrophages isolated with laser-capture microdissection in euglycemic and hyperglycemic HypoE mice. Hyperglycemia induced by streptozotocin treatment impaired lesion size reduction (36% versus 14%) and lipid loss (38% versus 26%) after the reversal of hyperlipidemia. However, decreases in lesional macrophage content and remodeling in both groups of mice were similar. Gene expression analysis revealed that hyperglycemia impaired cholesterol transport by modulating ATP-binding cassette A1, ATP-binding cassette G1, scavenger receptor class B family member (CD36), scavenger receptor class B1, and wound healing pathways in lesional macrophages during atherosclerosis regression. Hyperglycemia impairs both reduction in size and loss of lipids from atherosclerotic lesions upon plasma lipid lowering without significantly affecting the remodeling of the vascular wall.

  19. Deletion Diagnostics for Alternating Logistic Regressions

    PubMed Central

    Preisser, John S.; By, Kunthel; Perin, Jamie; Qaqish, Bahjat F.

    2013-01-01

    Deletion diagnostics are introduced for the regression analysis of clustered binary outcomes estimated with alternating logistic regressions, an implementation of generalized estimating equations (GEE) that estimates regression coefficients in a marginal mean model and in a model for the intracluster association given by the log odds ratio. The diagnostics are developed within an estimating equations framework that recasts the estimating functions for association parameters based upon conditional residuals into equivalent functions based upon marginal residuals. Extensions of earlier work on GEE diagnostics follow directly, including computational formulae for one-step deletion diagnostics that measure the influence of a cluster of observations on the estimated regression parameters and on the overall marginal mean or association model fit. The diagnostic formulae are evaluated with simulations studies and with an application concerning an assessment of factors associated with health maintenance visits in primary care medical practices. The application and the simulations demonstrate that the proposed cluster-deletion diagnostics for alternating logistic regressions are good approximations of their exact fully iterated counterparts. PMID:22777960

  20. On regression adjustment for the propensity score.

    PubMed

    Vansteelandt, S; Daniel, R M

    2014-10-15

    Propensity scores are widely adopted in observational research because they enable adjustment for high-dimensional confounders without requiring models for their association with the outcome of interest. The results of statistical analyses based on stratification, matching or inverse weighting by the propensity score are therefore less susceptible to model extrapolation than those based solely on outcome regression models. This is attractive because extrapolation in outcome regression models may be alarming, yet difficult to diagnose, when the exposed and unexposed individuals have very different covariate distributions. Standard regression adjustment for the propensity score forms an alternative to the aforementioned propensity score methods, but the benefits of this are less clear because it still involves modelling the outcome in addition to the propensity score. In this article, we develop novel insights into the properties of this adjustment method. We demonstrate that standard tests of the null hypothesis of no exposure effect (based on robust variance estimators), as well as particular standardised effects obtained from such adjusted regression models, are robust against misspecification of the outcome model when a propensity score model is correctly specified; they are thus not vulnerable to the aforementioned problem of extrapolation. We moreover propose efficient estimators for these standardised effects, which retain a useful causal interpretation even when the propensity score model is misspecified, provided the outcome regression model is correctly specified.

  1. Symbolic Regression of Conditional Target Expressions

    NASA Astrophysics Data System (ADS)

    Korns, Michael F.

    This chapter examines techniques for improving symbolic regression systems in cases where the target expression contains conditionals. In three previous papers we experimentedwith combining high performance techniques fromthe literature to produce a large scale, industrial strength, symbolic regression-classification system. Performance metrics across multiple problems show deterioration in accuracy for problems where the target expression contains conditionals. The techniques described herein are shown to improve accuracy on such conditional problems. Nine base test cases, from the literature, are used to test the improvement in accuracy. A previously published regression system combining standard genetic programming with abstract expression grammars, particle swarm optimization, differential evolution, context aware crossover and age-layered populations is tested on the nine base test cases. The regression system is enhanced with these additional techniques: pessimal vertical slicing, splicing of uncorrelated champions via abstract conditional expressions, and abstract mutation and crossover. The enhanced symbolic regression system is applied to the nine base test cases and an improvement in accuracy is observed.

  2. MULTILINEAR TENSOR REGRESSION FOR LONGITUDINAL RELATIONAL DATA.

    PubMed

    Hoff, Peter D

    2015-09-01

    A fundamental aspect of relational data, such as from a social network, is the possibility of dependence among the relations. In particular, the relations between members of one pair of nodes may have an effect on the relations between members of another pair. This article develops a type of regression model to estimate such effects in the context of longitudinal and multivariate relational data, or other data that can be represented in the form of a tensor. The model is based on a general multilinear tensor regression model, a special case of which is a tensor autoregression model in which the tensor of relations at one time point are parsimoniously regressed on relations from previous time points. This is done via a separable, or Kronecker-structured, regression parameter along with a separable covariance model. In the context of an analysis of longitudinal multivariate relational data, it is shown how the multilinear tensor regression model can represent patterns that often appear in relational and network data, such as reciprocity and transitivity.

  3. A New Robust Method for Nonlinear Regression.

    PubMed

    Tabatabai, M A; Kengwoung-Keumo, J J; Eby, W M; Bae, S; Manne, U; Fouad, M; Singh, K P

    When outliers are present, the least squares method of nonlinear regression performs poorly. The main purpose of this paper is to provide a robust alternative technique to the Ordinary Least Squares nonlinear regression method. This new robust nonlinear regression method can provide accurate parameter estimates when outliers and/or influential observations are present. Real and simulated data for drug concentration and tumor size-metastasis are used to assess the performance of this new estimator. Monte Carlo simulations are performed to evaluate the robustness of our new method in comparison with the Ordinary Least Squares method. In simulated data with outliers, this new estimator of regression parameters seems to outperform the Ordinary Least Squares with respect to bias, mean squared errors, and mean estimated parameters. Two algorithms have been proposed. Additionally and for the sake of computational ease and illustration, a Mathematica program has been provided in the Appendix. The accuracy of our robust technique is superior to that of the Ordinary Least Squares. The robustness and simplicity of computations make this new technique more appropriate and useful tool for the analysis of nonlinear regressions.

  4. A regression method for modelling geometric rates.

    PubMed

    Bottai, Matteo

    2015-09-18

    The occurrence of an event of interest over time is often summarized by the incidence rate, defined as the average number of events per person-time. This type of rate applies to events that may occur repeatedly over time on any given subject, such as infections, and Poisson regression represents a natural regression method for modelling the effect of covariates on it. However, for events that can occur only once, such as death, the geometric rate may be a better summary measure. The geometric rate has long been utilized in demography for studying the growth of populations and in finance to compute compound interest on capital. This type of rate, however, is virtually unknown to medical research. This may be partly a consequence of the lack of a regression method for it. This paper describes a regression method for modelling the effect of covariates on the geometric rate. The described method is based on applying quantile regression to a transform of the time-to-event variable. The proposed method is used to analyze mortality in a randomized clinical trial and in an observational epidemiological study.

  5. Regression models for estimating coseismic landslide displacement

    USGS Publications Warehouse

    Jibson, R.W.

    2007-01-01

    Newmark's sliding-block model is widely used to estimate coseismic slope performance. Early efforts to develop simple regression models to estimate Newmark displacement were based on analysis of the small number of strong-motion records then available. The current availability of a much larger set of strong-motion records dictates that these regression equations be updated. Regression equations were generated using data derived from a collection of 2270 strong-motion records from 30 worldwide earthquakes. The regression equations predict Newmark displacement in terms of (1) critical acceleration ratio, (2) critical acceleration ratio and earthquake magnitude, (3) Arias intensity and critical acceleration, and (4) Arias intensity and critical acceleration ratio. These equations are well constrained and fit the data well (71% < R2 < 88%), but they have standard deviations of about 0.5 log units, such that the range defined by the mean ?? one standard deviation spans about an order of magnitude. These regression models, therefore, are not recommended for use in site-specific design, but rather for regional-scale seismic landslide hazard mapping or for rapid preliminary screening of sites. ?? 2007 Elsevier B.V. All rights reserved.

  6. The effect of equine chorionic gonadotropin on follicular size, luteal volume, circulating progesterone concentrations, and pregnancy rates in anestrous beef cows treated with a novel fixed-time artificial insemination protocol.

    PubMed

    Dorneles Tortorella, Rodrigo; Ferreira, Rogério; Tonellotto Dos Santos, Joabel; Silveira de Andrade Neto, Olmiro; Barreta, Marcos Henrique; Oliveira, João Francisco; Gonçalves, Paulo Bayard; Pereira Neves, Jairo

    2013-05-01

    The objective was to determine the effects of eCG given on the day of, or 2 days before removal of an intravaginal progestin device, on ovarian follicle diameter, luteal volume, serum progesterone (P4) concentrations, and pregnancy per insemination in a fixed-time AI (FTAI) protocol. Lactating, anestrous, multiparous Bos taurus cross beef cows, 40 to 60 days postpartum, were given estradiol benzoate (2 mg im) and a progestin intravaginal device containing 250 mg of medroxyprogesterone acetate on Day 0 and cloprostenol (0.265 mg) on Day 6. Intravaginal devices were removed on Day 8 and GnRH (100 μg im) was given on Day 9, with timed AI 16 hours later. In experiment 1, cows were randomly assigned to receive 400 IU im eCG on Day 6 (eCG6; N = 8) or Day 8 (eCG8; N = 8), or to not receive eCG (control; N = 8). Dominant follicle diameter on Day 9 in the eCG6 group (10.0 ± 0.5 mm) was larger (P < 0.05) than in the eCG8 (8.6 ± 0.2 mm) or control (8.5 ± 0.4 mm) groups. Corpora lutea (CL) in all cows in the control group underwent premature luteolysis within 10 days after ovulation. Luteal volumes and P4 concentrations 10 and 15 days after ovulation were higher (P < 0.05) in the eCG6 group than in the eCG8 group. In experiment 2, the eCG6 (N = 121) and eCG8 (N = 125) protocols were compared in lactating anestrous cows that underwent FTAI. Pregnancy rate was higher (P < 0.05) in the cows that received eCG on Day 6 (27.3%; 33/121) than on Day 8 (16.0%; 20/125). Furthermore, CL volumes and P4 concentrations were higher (P < 0.05) in the eCG6 group (5784.0 ± 857.3 mm(3) and 8.1 ± 1.3 ng/mL, respectively) than in the eCG8 group (3220.9 ± 505.1 mm(3) and 4.5 ± 0.7 ng/mL, respectively). We concluded that eCG given 2 days before progestin removal in this FTAI protocol for anestrous beef cows increased diameter of the dominant follicle, luteal volume, serum P4 concentrations, and pregnancy rates. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Luteal expression of cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, and 20alpha-hydroxysteroid dehydrogenase genes in late pregnant rats: effect of luteinizing hormone and RU486.

    PubMed

    Stocco, C O; Chedrese, J; Deis, R P

    2001-10-01

    A decrease in serum progesterone at the end of pregnancy is essential for the induction of parturition in rats. We have previously demonstrated that LH participates in this process through: 1) inhibiting 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and 2) stimulating progesterone catabolism by inducing 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity. The objective of this investigation was to determine the effect of LH and progesterone on the luteal expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450(scc)), 3beta-HSD, and 20alpha-HSD genes. Gene expression was analyzed by Northern blot analysis 24 and 48 h after administration of LH or vehicle on Day 19 of pregnancy. StAR and 3beta-HSD mRNA levels were lower in LH-treated rats than in rats administered with vehicle at both time points studied. P450(scc) mRNA levels were unaffected by LH. The 20alpha-HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, greater expression of 20alpha-HSD, with respect to controls, was observed in LH-treated rats 48 h after treatment. Luteal progesterone content dropped in LH-treated rats at both time points studied, whereas serum progesterone decreased after 48 h only. In a second set of experiments, the anti-progesterone RU486 was injected intrabursally on Day 20 of pregnancy. RU486 had no effect on 3beta-HSD or P450(scc) expression but increased 20alpha-HSD mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3beta-HSD expression without effect on P450(scc) expression. We also provide the first in vivo evidence indicating that a decrease in luteal progesterone content may be an essential step toward the induction of 20alpha-HSD expression at the end of pregnancy in rats.

  8. Effect of fish oil on lateral mobility of prostaglandin F2α (FP) receptors and spatial distribution of lipid microdomains in bovine luteal cell plasma membrane in vitro.

    PubMed

    Plewes, M R; Burns, P D; Graham, P E; Hyslop, R M; Barisas, B G

    2017-01-01

    Lipid microdomains are ordered regions on the plasma membrane of cells, rich in cholesterol and sphingolipids, ranging in size from 10 to 200 nm in diameter. These lipid-ordered domains may serve as platforms to facilitate colocalization of intracellular signaling proteins during agonist-induced signal transduction. It is hypothesized that fish oil will disrupt the lipid microdomains, increasing spatial distribution of these lipid-ordered domains and lateral mobility of the prostaglandin (PG) F2α (FP) receptors in bovine luteal cells. The objectives of this study were to examine the effects of fish oil on (1) the spatial distribution of lipid microdomains, (2) lateral mobility of FP receptors, and (3) lateral mobility of FP receptors in the presence of PGF2α on the plasma membrane of bovine luteal cells in vitro. Bovine ovaries were obtained from a local abattoir and corpora lutea were digested using collagenase. In experiment 1, lipid microdomains were labeled using cholera toxin subunit B Alexa Fluor 555. Domains were detected as distinct patches on the plasma membrane of mixed luteal cells. Fish oil treatment decr