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Sample records for fibroblasts stimulate uterine

  1. Stromal fibroblast activation and their potential association with uterine fibroids (Review)

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    ZHENG, LI-HUA; CAI, FENG-FENG; GE, ISABELL; BISKUP, EWELINA; CHENG, ZHONG-PING

    2014-01-01

    Uterine fibroids are the most common type of benign, gynecologic neoplasm and are the primary indication for performance of a hysterectomy, accounting for >200,000 hysterectomies annually in the USA. At present, females are younger and exhibit larger leiomyomas at the time of diagnosis. Cancer-associated fibroblasts in tumor microenvironments have emerged as an important target for cancer therapy. Repeated stimulation by infectious or non-infectious agents in the uterine tissues, including inflammation, mechanical forces or hypoxia, stimulate the resident fibroblasts to undergo specific activation and, thus, are significant in tumorigenesis. Furthermore, complex signaling pathways regulate the mechanisms of fibroblastic activation. The current review focuses on the molecular mechanisms of fibroblastic activation and the potential association with uterine leiomyoma pathogenesis, enabling an integrated pathogenic analysis for review of the therapeutic options. PMID:25013460

  2. Uterine responses to three techniques of breast stimulation.

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    Curtis, P; Evens, S; Resnick, J; Rimer, R; Lynch, K; Carlson, J R

    1986-01-01

    Uterine contractions produced by three methods of breast stimulation and a placebo were compared in 202 high-risk women between 35 and 44 weeks' gestation during contraction stress tests. Manual stimulation produced significantly more successful responses of three or more contractions within ten minutes than did a heating pad or a placebo, but did not show significant differences when compared with a breast pump. The placebo group showed an increase in contractions over a resting state. Of the women with successful contraction stress tests, over 50% demonstrated exaggerated uterine activity (a hypertonic contraction of greater than 90 seconds, or five or more contractions in a ten-minute period).

  3. HGF is released from buccal fibroblasts after smokeless tobacco stimulation

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    Dabelsteen, S; Christensen, S; Gron, B

    2005-01-01

    To investigate the effect of smokeless tobacco (ST) on (1) HGF, KGF and GM-CSF expression by buccal fibroblasts and (2) on keratinocyte and fibroblast proliferation. Buccal fibroblasts were stimulated with different concentrations of ST extracts in a double dilution from 0.50% w/v to 0.03% w...... on exposure time and on concentration of the tobacco extract. High concentration increased production of HGF 4-fold. KGF production was doubled when high concentration of tobacco was used, low concentration did not stimulate cells. GM-CSF production was low in both stimulated and non-stimulated cells...

  4. Transmission of HIV-1 by primary human uterine epithelial cells and stromal fibroblasts.

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    Asin, Susana N; Fanger, Michael W; Wildt-Perinic, Dunja; Ware, Patricia L; Wira, Charles R; Howell, Alexandra L

    2004-07-15

    Women can become infected with human immunodeficiency virus type 1 (HIV-1) after the heterosexual transmission of virus from an infected male partner. To understand the events that result in transmission of HIV-1 across the female reproductive tract, we characterized the life-cycle events of HIV-1 in primary cultures of human uterine epithelial cells and stromal fibroblasts. Epithelial cells and stromal fibroblasts released virus particles after exposure to either X4- or R5-tropic strains of HIV-1. Virus released by these cells was able to infect CD4(+) T cells. When exposed to an X4-tropic strain of HIV-1, these cells supported HIV-1 reverse transcription, integration, and viral DNA transcription. When exposed to an R5-tropic strain, however, these cells released unmodified virus. These data suggest that uterine cells are targets for productive infection with X4-tropic strains and release unmodified R5-tropic viruses that would then be able to infect submucosal target cells, including T cells and macrophages.

  5. Uterine contractility and blood flow are reflexively regulated by cutaneous afferent stimulation in anesthetized rats.

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    Hotta, H; Uchida, S; Shimura, M; Suzuki, H

    1999-01-15

    The effects of cutaneous mechanical afferent stimulation of various skin areas on uterine contractility and blood flow were examined in anesthetized non-pregnant rats. The contractility of the uterus was measured by the balloon method in the uterus. The uterine blood flow was measured by laser Doppler flowmetry. Noxious pinching stimulation of the perineum for 1 min induced an abrupt contraction of the uterus during stimulation. Pinching of a hindpaw or perineum and innocuous brushing of the perineum for 1 min increased uterine blood flow. Stimulation of other skin areas produced no changes in uterine contractility or blood flow. Most uterine responses were abolished by severance of the pelvic nerves, which innervated the uterus. The activity of pelvic parasympathetic efferent nerves to the uterus increased following perineal pinching. All these cutaneous stimulation-induced responses of uterine contractility, blood flow and pelvic efferent nerve activity still existed, and were even augmented, after acute spinalization. These results indicate that cutaneous mechanical sensory stimulation can regulate uterine contractility and blood flow by a segmental spinal reflex mechanism via uterine parasympathetic efferent nerves.

  6. Stimulation of fetal hypothalamus induces uterine contractions in pregnant rats at term.

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    Endoh, Hisashi; Fujioka, Takashi; Endo, Hideki; Inazuka, Yukiko; Furukawa, Susumu; Nakamura, Shoji

    2008-10-01

    The fetal brain is thought to have a role in the onset and progression of labor. Evidence also exists for fetal oxytocin release just before and during parturition. The present study examined whether activation of the fetal brain could induce uterine myometrial contractions through oxytocin receptors in the dam. Under urethane anesthesia, electrical stimulation of the hypothalamus of fetal rats that were still connected with the dams by an intact umbilical cord induced uterine contractions in term pregnant rats. Intraperitoneal injections of synthetic oxytocin in fetuses induced uterine contractions in the dams similar to those induced by electrical stimulation of the fetal hypothalamus. Maternal intravenous injections of an oxytocin antagonist immediately attenuated uterine contractions induced by fetal oxytocin injections and electrical stimulation of the fetal hypothalamus. These findings suggest the possibility that oxytocin released from the fetal hypothalamus is involved in parturition.

  7. High molecular weight plant heteropolysaccharides stimulate fibroblasts but inhibit keratinocytes.

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    Shahbuddin, Munira; Shahbuddin, Dahlia; Bullock, Anthony J; Ibrahim, Halijah; Rimmer, Stephen; MacNeil, Sheila

    2013-06-28

    Konjac glucomannan (KGM) is a natural polysaccharide of β(1-4)-D-glucomannopyranosyl backbone of D-mannose and D-glucose derived from the tuber of Amorphophallus konjac C. Koch. KGM has been reported to have a wide range of activities including wound healing. In this study we examined KGM extracts prepared from five plant species, (Amorphophallus konjac Koch, Amorphophallus oncophyllus, Amorphophallus prainii, Amorphophallus paeoniifolius and Amorphophallus elegans) for their effects on cultured human keratinocytes and fibroblasts. Extracts from A. konjac Koch, A. oncophyllus and A. prainii (but not from A. paeoniifolius or A. elegans) stimulated fibroblast proliferation both in the absence and presence of serum. However, these materials inhibited keratinocyte proliferation. The fibroblast stimulatory activity was associated with high molecular weight fractions of KGM and was lost following ethanol extraction or enzyme digestion with β-mannanase. It was also reduced by the addition of concanavalin A but not mannose suggesting that these heteropolysaccharides are acting on lectins but not via receptors specific to mannose. The most dramatic effect of KGM was seen in its ability to support fibroblasts for 3weeks under conditions of deliberate media starvation. This effect did not extend to supporting keratinocytes under conditions of media starvation but KGM did significantly help support adipose derived stem cells under media starvation conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Growth stimulation of 3T3 fibroblasts by Cystatin

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    Quan Sun (Michigan State Univ., East Lansing (United States) Beijing Medical Univ. (China))

    1989-01-01

    Treatment of cultures of mouse 3T3 fibroblasts with Cystatin C, a thiol-proteinase inhibitor isolated from chicken egg white, resulted in an enhanced rate of cell proliferation. This stimulation was demonstrated using two independent assay systems: (a) assessment of total cell number and (b) measurement of ({sup 3}H)thymidine incorporated into acid-precipitable DNA. In both assays, the dose-response curves of Cystatin stimulation showed a rising function that plateaued at a concentration of {approximately}120 {mu}g/ml. The addition of Cystatin to cultures of Kirsten murine sarcoma virus-transformed 3T3 cells also enhanced DNA synthesis in these target cells. Control experiments showed that the presence of Cystatin did not alter the level of binding of radioactively labeled epidermal growth factor and platelet derived growth factor to 3T3 cells. These results argue against the possibility that the observed growth stimulation by Cystatin was due to growth factor contamination of the Cystatin preparation.

  9. A FTIR imaging characterization of fibroblasts stimulated by various breast cancer cell lines.

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    Saroj Kumar

    Full Text Available It is well known that the microenvironment plays a major role in breast cancer progression. Yet, the mechanism explaining the transition from normal fibroblasts to cancer-stimulated fibroblasts remains to be elucidated. Here we report a FTIR imaging study of the effects of three different breast cancer cell lines on normal fibroblasts in culture. Fibroblast activation process was monitored by FTIR imaging and spectra compared by multivariate statistical analyses. Principal component analysis evidenced that the fibroblasts stimulated by these cancer cell lines grouped together and remained distinctly separated from normal fibroblasts indicating a modified different chemical composition in the cancer-stimulated fibroblasts. Similar changes in fibroblasts were induced by the various breast cancer cell lines belonging to different sub-types. Most significant changes were observed in the region of 2950 and 1230 cm(-1, possibly related to changes in lipids and in the 1230 cm(-1 area assigned to phosphate vibrations (nucleotides. Interestingly, the cancer-cell induced changes in the fibroblasts also occurred when there was no possible direct contact between the two cell lines in the co-culture. When contact was possible, the spectral changes were similar, suggesting that soluble factors but not direct cell-cell interactions were responsible for fibroblast activation. Overall, the results indicate that IR imaging could be used in the future for analyzing the microenvironment of breast tumors.

  10. Association of uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination for unexplained infertility.

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    Styer, Aaron K; Jin, Susan; Liu, Dan; Wang, Baisong; Polotsky, Alex J; Christianson, Mindy S; Vitek, Wendy; Engmann, Lawrence; Hansen, Karl; Wild, Robert; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter; Christman, Gregory M; Christy, Alicia; Diamond, Michael P; Eisenberg, Esther; Zhang, Heping; Santoro, Nanette

    2017-03-01

    To investigate the association of non-cavity-distorting uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination (OS-IUI) in couples with unexplained infertility. Secondary analysis from a prospective, randomized, multicenter clinical trial investigating fertility outcomes after OS-IUI. Reproductive Medicine Network clinical sites. Nine hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. Participants were randomized to one of three arms (clomiphene citrate, letrozole, or gonadotropins), and treatment was continued for up to four cycles or until pregnancy was achieved. Conception (serum hCG increase), clinical pregnancy (fetal cardiac activity), and live birth rates. A total of 102/900 participants (11.3%) had at least one documented fibroid and a normal uterine cavity. Women with fibroids were older, more likely to be African American, had a greater uterine volume, lower serum antimüllerian hormone levels, and fewer antral follicles than women without fibroids. In conception cycles, clinical pregnancy rates were significantly lower in participants with fibroids than in those without uterine fibroids. Pregnancy loss before 12 weeks was more likely in African American women with fibroids compared with non-African American women with fibroids. There was no difference in conception and live birth rates in subjects with and without fibroids. No differences were observed in conception and live birth rates in women with non-cavity-distorting fibroids and those without fibroids. These findings provide reassurance that pregnancy success is not impacted in couples with non-cavity-distorting fibroids undergoing OS-IUI for unexplained infertility. NCT01044862. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration.

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    Mackey, Abigail L; Magnan, Mélanie; Chazaud, Bénédicte; Kjaer, Michael

    2017-08-01

    Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. The extent of cross-talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell-culture studies. We observed a strong stimulation of myogenesis by human fibroblasts in cell culture. In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross-talk during physiological and pathological muscle remodelling. Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross-sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co-cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable

  12. Stimulation of mating-induced uterine contractions in the bitch and their modification and enhancement of fertility by prostatic fluid.

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    England, G C W; Moxon, R; Freeman, S L

    2012-12-01

    Little is known about the response of the bitch's reproductive tract to mating or of the role of male accessory gland secretions in the female. In this clinical study, the component stimuli causing mating-induced uterine contractions were investigated in 64 bitches. Basal uterine contractions were present during oestrus and a significant increase in the frequency of contractions was observed during natural mating. Neither teasing with a male nor stimulation of the vagina or cervix by vaginal or transcervical insemination (TCI) caused an increase in the frequency of uterine contractions. Increased contractions were however present after both vaginal and transcervical insemination when the vestibule was distended, and dorsal wall of the vaginal was manually stimulated. Interestingly, this increase in uterine contractions was partially ameliorated when prostatic fluid was used as a flushing component following transcervical insemination. Two further studies performed with 72 bitches of which 18 were each inseminated transcervically with fresh or frozen semen flushed into the uterus with either saline or prostatic fluid demonstrated that prostatic fluid significantly increased the pregnancy rate and litter size of both groups. There are important mechanisms regulating the transport and elimination of sperm from the bitch's reproductive tract. Whilst physical aspects of coitus are undoubtedly involved in initiating uterine contractions, prostatic fluid appears to have an important role in modulating uterine contractions and fertility.

  13. Platelets stimulate fibroblast-mediated contraction of collagen gels

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    Lundahl Joachim

    2003-10-01

    Full Text Available Abstract Background Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF and transforming growth factor-β (TGF-β contribute to this effect. Methods Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing, were cast together with human lung fibroblasts in three-dimensional collagen gels. The gels were then released and cultured for four days. PDGF and TGF-β1 concentrations were measured in culture supernatants by ELISA. Results Both platelets and platelet lysate augmented fibroblast-mediated gel contraction in a time and concentration dependent manner (19.9% ± 0.1 (mean ± SEM of initial area vs. 48.0% ± 0.4 at 48 hours; P 1 and PDGF-AA/AB were released in co-culture. PDGF-AA/AB had a maximum release at 24 hours whereas TGF-β1 release increased with longer culture periods. Neutralising antibodies to these mediators partially inhibited platelet-induced gel contraction. Conclusion We conclude that platelets may promote remodelling of extracellular matrix in vitro and that PDGF and TGF-β partially mediate this effect, also indicating a role for other mediators. The findings may be an important mechanism in regulating repair processes after injury.

  14. Nicotine stimulates nerve growth factor in lung fibroblasts through an NFκB-dependent mechanism.

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    Cherry Wongtrakool

    Full Text Available Airway hyperresponsiveness (AHR is classically found in asthma, and persistent AHR is associated with poor asthma control. Although airway smooth muscle (ASM cells play a critical pathophysiologic role in AHR, the paracrine contributions of surrounding cells such as fibroblasts to the contractile phenotype of ASM cells have not been examined fully. This study addresses the hypothesis that nicotine promotes a contractile ASM cell phenotype by stimulating fibroblasts to increase nerve growth factor (NGF secretion into the environment.Primary lung fibroblasts isolated from wild type and α7 nicotinic acetylcholine receptor (α7 nAChR deficient mice were treated with nicotine (50 µg/ml in vitro for 72 hours. NGF levels were measured in culture media and in bronchoalveolar lavage (BAL fluid from asthmatic, smoking and non-smoking subjects by ELISA. The role of the NFκB pathway in nicotine-induced NGF expression was investigated by measuring NFκB nuclear translocation, transcriptional activity, chromatin immunoprecipitation assays, and si-p65 NFκB knockdown. The ability of nicotine to stimulate a fibroblast-mediated, contractile ASM cell phenotype was confirmed by examining expression of contractile proteins in ASM cells cultured with fibroblast-conditioned media or BAL fluid.NGF levels were elevated in the bronchoalveolar lavage fluid of nicotine-exposed mice, current smokers, and asthmatic children. Nicotine increased NGF secretion in lung fibroblasts in vitro in a dose-dependent manner and stimulated NFκB nuclear translocation, p65 binding to the NGF promoter, and NFκB transcriptional activity. These responses were attenuated in α7 nAChR deficient fibroblasts and in wild type fibroblasts following NFκB inhibition. Nicotine-treated, fibroblast-conditioned media increased expression of contractile proteins in ASM cells.Nicotine stimulates NGF release by lung fibroblasts through α7 nAChR and NFκB dependent pathways. These novel findings

  15. Granulocyte macrophage colony stimulating factor (GM-CSF biological actions on human dermal fibroblasts

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    S Montagnani

    2009-12-01

    Full Text Available Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GMCSFR on human normal skin fibroblasts from healthy subjects (NFPC and on a human normal fibroblast cell line (NHDF and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GMCSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such “differentiation” is an important event induced by such cytokine.

  16. Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion.

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    Philip Owens

    Full Text Available Bone Morphogenetic Proteins (BMPs are secreted cytokines that are part of the Transforming Growth Factor β (TGFβ superfamily. BMPs have been shown to be highly expressed in human breast cancers, and loss of BMP signaling in mammary carcinomas has been shown to accelerate metastases. Interestingly, other work has indicated that stimulation of dermal fibroblasts with BMP can enhance secretion of pro-tumorigenic factors. Furthermore, treatment of carcinoma-associated fibroblasts (CAFs derived from a mouse prostate carcinoma with BMP4 was shown to stimulate angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases (MMPs were found to be upregulated in response to BMP4 treatment. Fibroblasts that were stimulated with BMP4 were found to enhance mammary carcinoma cell invasion, and these effects were inhibited by a BMP receptor kinase antagonist. Treatment with BMP in turn elevated pro-tumorigenic secreted factors such as IL-6 and MMP-3. These experiments demonstrate that BMP may stimulate tumor progression within the tumor microenvironment.

  17. Influence of mechanical stimulation on human dermal fibroblasts derived from different body sites.

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    Kuang, Ruixia; Wang, Zhiguo; Xu, Quanchen; Liu, Su; Zhang, Weidong

    2015-01-01

    Mechanical stimulation is highly associated with pathogenesis of human hypertrophic scar. Although much work has focused on the influence of mechanical stress on fibroblast populations from various tissues and organs in the human body, their effects on cultured dermal fibroblasts by the area of the body have not been as well studied. In this study, cultures of skin fibroblasts from two different body sites were subjected to cyclic mechanical stimulation with a 10% stretching amplitude at a frequency of 0.1 Hz for 24, 36 and 48 hours, respectively, and thereafter harvested for experimental assays. Fibroblasts from scapular upper back skin, subjected to mechanical loads for 36 and 48 hours, respectively, were observed to proliferate at a higher rate and reach confluent more rapidly during in vitro culturing, had higher expression levels of mRNA and protein production of integrin β1, p130Cas and TGF β1 versus those from medial side of upper arm. These data indicate that skin fibroblasts, with regard to originated body sites studied in the experiments, display a diversity of mechanotransduction properties and biochemical reactions in response to applied mechanical stress, which contributes to the increased susceptibility to hypertrophic scars formation at certain areas of human body characterized by higher skin and muscle tension.

  18. TNF-α-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation.

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    Pilling, Darrell; Vakil, Varsha; Cox, Nehemiah; Gomer, Richard H

    2015-09-22

    In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis.

  19. Effects of Baicalin on Expression of Inducible Nitric Oxide Synthase in Cultured Fibroblasts Stimulated by Cytokines

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    毕新岭; 顾军; 聂本勇; 李泉; 刘辉; 米庆胜

    2004-01-01

    Objective: To investigate the effects of baicalin on expression of inducible nitric oxide synthase (iNOS) in fibroblasts and its mechanisms in treating psoriasis. Methods: Fibroblasts cultured in vitro were stimulated with tumor necrosis factor-α(TNF-α), interferon-γ (IFN-γ), interleukin-8 (IL-S) in different groups. iNOS was detected by western blot and immunocytochemistry assay, and in addition, the effects of baicalin on its expression were investigated. Results: Fibroblasts did not express iNOS without cytokine stimulation. When treated for 24 h with 1. 0× 106 U/L TNF-α, 0.2× 106U/L IFN-γ, 0.2× 106 pg/L IL-8 alone or in combinations indicated, fibroblasts produced iNOS when stimulated by TNF-α alone while neither IFN-γ nor IL-8 could induce the production of iNOS. The combination of TNF-α and IL-8 induced a strong expression of iNOS, the combined exposure of three kinds of cytokines showed an even stronger effects. The strongly stained area was in the cytoplasm near the nuclei. Expression of iNOS induced by TNF-α and IL-8 was inhibited by 50 μg/ mi of baicalin. Conclusion: Fibroblasts might express iNOS when stimulated by certain cytokines. Baicalin decreased production of nitric oxide through inhibiting the expression of iNOS, furthermore it reduced inflammation, which might be part of its mechanisms in treating psoriasis.

  20. Effects of Balcalin on Expression of Inducible Nitric Oxide Synthase In Cultured Fibroblasts Stimulated by Cytokines

    Institute of Scientific and Technical Information of China (English)

    毕新岭; 顾军; 聂本勇; 李泉; 刘辉; 米庆胜

    2004-01-01

    Objective: To investigate the effects of baicalin on expression of inducible nitric oxide synthase (iNOS) in fibroblasts and its mechanisms in treating psoriasis. Methods: Fibroblasts cultured in vitro were stimulated with tumor necrosis factor-α((TNF-α), interferon-γ(IFN-γ), interleukin-8 (IL-8) in different groups, iNOS was detected by western blot and immunocytochemistry assay, and in addition, the effects of baicalin on its expression were investigated. Results. Fibroblasts did not express iNOS without cytokine stimulation. When treated for 24 h with 1.0×106 U/L TNF-α, 0.2×106U/L IFN-γ, 0.2×106 pg/L IL-8 alone or in combinations indicated, fibroblasts produced iNOS when stimulated by TNF-α alone while neither IFN-γ nor IL-8 could induce the production of iNOS. The combination of TNF-α and IL-8 induced a strong expression of iNOS, the combined exposure of three kinds of cytokines showed an even stronger effects. The strongly stained area was in the cytoplasm near the nuclei. Expression of iNOS induced by TNF-α and IL-8 was inhibited by 50μg/ ml of baicalin. Conclusion. Fibroblasts might express iNOS when stimulated by certain cytokines. Baicalin decreased production of nitric oxide through inhibiting the expression of iNOS, furthermore it reduced inflammation, which might be part of its mechanisms in treating psoriasis.

  1. Stimulation of reactive oxygen species and collagen synthesis by angiotensin II in cardiac fibroblasts.

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    Lijnen, Paul J; van Pelt, Jos F; Fagard, Robert H

    2012-02-01

    Superoxide anion generated by NAD(P)H-oxidase has an important role in the pathogenesis of cardiovascular diseases and scavenging superoxide anion can be considered as a reasonable therapeutic strategy. In hypertensive heart diseases there is a mutual reinforcement of reactive oxygen species (ROS) and angiotensin II (ANG II). ANG II increases the NAD(P)H-dependent superoxide anion production and the intracellular generation of ROS in cardiac fibroblasts and apocynin, a membrane NAD(P)H oxidase inhibitor, abrogates this rise. ANG II also stimulates the collagen production, the collagen I and III content and mRNA expression in cardiac fibroblasts and apocynin abolishes this induction. In this review we demonstrate that scavenging superoxide anion by tempol or EUK-8 or administration of PEG-superoxide dismutase (SOD) inhibits collagen production in cardiac fibroblasts. On the contrary increasing superoxide anion formation by inhibition of SOD stimulates collagen production. A vital role of SOD and the generated ROS can be suggested in the regulation and organization of collagen in cardiac fibroblasts. Specific pharmacological intervention with SOD mimetics can probably be an alternative approach for reducing myocardial fibrosis.

  2. Intra-cycle variation of the uterine cavity indentation assessed with three-dimensional ultrasound in natural and stimulated cycles.

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    Saravelos, Sotirios H; Li, Tin-Chiu

    2016-05-01

    The recent ESHRE-ESGE classification for female genital anomalies attempts to promote objectivity in diagnosis of normal and septate uteri. The aim of this study was to ascertain whether the uterine cavity indentation - the characteristic feature of septate uteri - varies significantly throughout the cycle. Seventy consecutive women underwent three-dimensional ultrasound twice: 35 during the proliferative and luteal phase of a natural cycle, and 35 during the first and final day of a stimulated cycle. Endometrial thickness, interostial distance, cavity indentation and percentage of cavity indentation were all assessed in accordance with the ESHRE-ESGE consensus on diagnosis of female genital anomalies. Overall, throughout both cycles, there was a significant increase in endometrial thickness (from 4.6 mm to 10.2 mm; P cavity indentation (from 30.3% to 15.0%; P uterine cavity indentation has important implications for both clinical practice and research.

  3. Chronic stimulation of uterine prostaglandin synthesis during cervical ripening before the onset of labor.

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    Keirse, M J; Thiery, M; Parewijck, W; Mitchell, M D

    1983-05-01

    Concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in plasma of six carefully selected primigravid women with an unripe cervix at term before and at various intervals after extra-amniotic insertion of a Foley catheter with or without methylhydroxyethylcellulose (Tylose) gel. The procedure caused an acute elevation of PGFM levels within 5 min (P less than 0.025), which was maintained for at least 6 hours in the absence of uterine activation at 179 +/- 32% of the initial values (P less than 0.01). Extra-amniotic administration of Tylose gel caused an increase in PGFM levels which was both higher and more prolonged (greater than 12 hours) than insertion of a Foley catheter alone. The observations indicate that cervical ripening without concomitant uterine activation is associated with an increase in PGFM levels. They also demonstrate that prolonged activation of (intra) uterine prostaglandin synthesis may occur several hours before the onset of labor-like uterine activity. A chance finding further suggests that spontaneous rupture of the membranes too may be preceeded by an increase in (intra) uterine prostaglandin synthesis. In their totality these observations lend strong support to the proposition that an increase in (intra) uterine prostaglandin production is a prerequisite to rather than a consequence of the initiation of labor.

  4. Effect of GnRH antagonist on follicular development and uterine biophysical profile in controlled ovarian stimulation

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    Bhawana Tiwary

    2015-02-01

    Full Text Available Background: Objective of current study was to assess the effect of GnRH antagonist on follicular development, premature luteinization, uterine biophysical profile and pregnancy rate in controlled ovarian stimulation with clomiphene and gonadotropins for intrauterine insemination in women with unexplained infertility. Methods: Randomised controlled trial. Minimal stimulation protocol with or without GnRH antagonist was compared. Setting: Infertility clinic, PGIMER, Chandigarh. Patients: Couples with unexplained infertility, age of female partner between 20-39 years. Intervention: GnRH antagonist 0.25 mg since follicle size 14 mm till hCG administration. Main outcome measures: Follicle characteristics, premature luteinisation, uterine biophysical profile and pregnancy rate. Results: The mean number of follicles recruited in group A was 2.32 +/- 1.01 while that in group B (receiving GnRH antagonist it was 4.10 +/- 1.69. Statistically significant increase in total biophysical profile score was observed in periovulatory phase in the antagonist group. 40% women in group A had premature luteinization whereas only 4% women in group B suffered from premature luteinization. 20% women who received GnRH antagonist conceived against only 6% in group A, this difference however was not statistically significant Conclusions: GnRH antagonist has a role in increasing the number of follicles recruited. Furthermore, GnRH antagonist can improve the total uterine biophysical profile score by improving the endometrial thickness, endometrial pattern, blood flow and decreasing the impedance to the blood flow in uterine artery. The drug can potentially help in improving pregnancy rates by decreasing the rate of premature luteinisation. [Int J Reprod Contracept Obstet Gynecol 2015; 4(1.000: 157-163

  5. Cyclic mechanical deformation stimulates human lung fibroblast proliferation and autocrine growth factor activity.

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    Bishop, J E; Mitchell, J J; Absher, P M; Baldor, L; Geller, H A; Woodcock-Mitchell, J; Hamblin, M J; Vacek, P; Low, R B

    1993-08-01

    Cellular hypertrophy and hyperplasia and increased extracellular matrix deposition are features of tissue hypertrophy resulting from increased work load. It is known, for example, that mechanical forces play a critical role in lung development, cardiovascular remodeling following pressure overload, and skeletal muscle growth. The mechanisms involved in these processes, however, remain unclear. Here we examined the effect of mechanical deformation on fibroblast function in vitro. IMR-90 human fetal lung fibroblasts grown on collagen-coated silastic membranes were subjected to cyclical mechanical deformation (10% increase in culture surface area; 1 Hz) for up to 5 days. Cell number was increased by 39% after 2 days of deformation (1.43 +/- .01 x 10(5) cells/membrane compared with control, 1.03 +/- 0.02 x 10(5) cells; mean +/- SEM; P < 0.02) increasing to 163% above control by 4 days (2.16 +/- 0.16 x 10(5) cells compared with 0.82 +/- 0.03 x 10(5) cells; P < 0.001). The medium from mechanically deformed cells was mitogenic for IMR-90 cells, with maximal activity in the medium from cells mechanically deformed for 2 days (stimulating cell replication by 35% compared with media control; P < 0.002). These data suggest that mechanical deformation stimulates human lung fibroblast replication and that this effect is mediated by the release of autocrine growth factors.

  6. Altered beta-adrenergic receptor-stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors.

    Science.gov (United States)

    Huang, H M; Gibson, G E

    1993-07-15

    An alteration in signal transduction systems in Alzheimer's disease would likely be of pathophysiological significance, because these steps are critical to normal brain function. Since dynamic processes are difficult to study in autopsied brain, the current studies utilized cultured skin fibroblasts. The beta-adrenergic-stimulated increase in cAMP was reduced approximately 80% in fibroblasts from Alzheimer's disease compared with age-matched controls. The deficit in Alzheimer fibroblasts in response to various adrenergic agonists paralleled their beta-adrenergic potency, and enhancement of cAMP accumulation by a non-adrenergic agonist, such as prostaglandin E1, was similar in Alzheimer and control fibroblasts. Diminished adenylate cyclase activity did not underlie these abnormalities, since direct stimulation of adenylate cyclase by forskolin elevated cAMP production equally in Alzheimer and control fibroblasts. Cholera toxin equally stimulated cAMP formation in Alzheimer and control fibroblasts. Moreover, cholera toxin partially reduced isoproterenol-induced cAMP deficit in Alzheimer fibroblasts. Pertussis toxin, on the other hand, did not alter the Alzheimer deficits. The results suggest either that the coupling of the GTP-binding protein(s) to the beta-adrenergic receptor is abnormal or that the sensitivity of receptor is altered with Alzheimer's disease. Further, any hypothesis about Alzheimer's disease must explain why a reduced beta-adrenergic-stimulated cAMP formation persists in tissue culture.

  7. Fibroblast growth factor 9 activates akt and MAPK pathways to stimulate steroidogenesis in mouse leydig cells.

    Science.gov (United States)

    Lai, Meng-Shao; Cheng, Yu-Sheng; Chen, Pei-Rong; Tsai, Shaw-Jenq; Huang, Bu-Miin

    2014-01-01

    Fibroblast growth factor 9 (FGF9) is a multifunctional polypeptide belonging to the FGF family and has functions related to bone formation, lens-fiber differentiation, nerve development, gap-junction formation and sex determination. In a previous study, we demonstrated that FGF9 stimulates the production of testosterone in mouse Leydig cells. In the present study, we used both primary mouse Leydig cells and MA-10 mouse Leydig tumor cells to further investigate the molecular mechanism of FGF9-stimulated steroidogenesis. Results showed that FGF9 significantly activated steroidogenesis in both mouse primary and tumor Leydig cells (psteroidogenesis in mouse Leydig cells. In conclusion, FGF9 specifically activated the Akt and ERK1/2 in normal mouse Leydig cells and the Akt, JNK and ERK1/2 in MA-10 mouse Leydig tumor cells to stimulate steroidogenesis.

  8. PGE2 signaling through the EP4 receptor on fibroblasts upregulates RANKL and stimulates osteolysis.

    Science.gov (United States)

    Tsutsumi, Ryosuke; Xie, Chao; Wei, Xiaochao; Zhang, Minjie; Zhang, Xinping; Flick, Lisa M; Schwarz, Edward M; O'Keefe, Regis J

    2009-10-01

    Periprosthetic osteolysis is the most common cause of aseptic loosening in total joint arthroplasty. The role of inflammatory mediators such as prostaglandin E2 (PGE2) and osteoclast promoting factors including RANKL in the pathogenesis of osteolysis has been well characterized. However, the PGE2 receptor (EP1, EP2, or EP4), and cell type in which it is expressed, which is responsible for PGE2 induction of RANKL during wear debris-induced osteolysis, has yet to be elucidated. To address this, we used mice genetically deficient in these EP receptors to assess PGE2 and wear debris responses in vitro and in vivo. Wear debris-induced osteolysis and RANKL expression were observed at similar levels in WT, EP1(-/-), and EP2(-/-) mice, indicating that these receptors do not mediate PGE2 signals in this process. A conditional knockout approach was used to eliminate EP4 expression in FSP1(+) fibroblasts that are the predominant source of RANKL. In the absence of EP4, fibroblasts do not express RANKL after stimulation with particles or PGE2, nor do they exhibit high levels of osteoclasts and osteolysis. These results show that periprosthetic fibroblasts are important mediators of osteolysis through the expression of RANKL, which is induced after PGE2 signaling through the EP4 receptor.

  9. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

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    Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola, E-mail: ola.hammarsten@clinchem.gu.se

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.

  10. The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue

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    Li Qi-Jing

    2002-06-01

    Full Text Available Abstract Background During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF, is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds.

  11. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation.

    Science.gov (United States)

    Mathew, Sherin T; Bergström, Petra; Hammarsten, Ola

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Late infusion of cloned marrow fibroblasts stimulates endogenous recovery from radiation-induced lung injury.

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    Mineo Iwata

    Full Text Available In the current study, we used a canine model of radiation-induced lung injury to test the effect of a single i.v. infusion of 10×10(6/kg of marrow fibroblasts on the progression of damage following 15 Gy exposure to the right lung. The fibroblasts, designated DS1 cells, are a cloned population of immortalized cells isolated from a primary culture of marrow stromal cells. DS1 cells were infused at week 5 post-irradiation when lung damage was evident by imaging with high-resolution computed tomography (CT. At 13 weeks post-irradiation we found that 4 out of 5 dogs receiving DS1 cells had significantly improved pulmonary function compared to 0 out of 5 control dogs (p = 0.047, Fisher's Exact. Pulmonary function was measured as the single breath diffusion capacity-hematocrit (DLCO-Hct, the total inspiratory capacity (IC, and the total lung capacity (TLC, which differed significantly between control and DS1-treated dogs; p = 0.002, p = 0.005, and p = 0.004, respectively. The DS1-treated dogs also had less pneumonitis detected by CT imaging and an increased number of TTF-1 (thyroid transcription factor 1, NKX2-1 positive cells in the bronchioli and alveoli compared to control dogs. Endothelial-like progenitor cells (ELC of host origin, detected by colony assays, were found in peripheral blood after DS1 cell infusion. ELC numbers peaked one day after infusion, and were not detectable by 7 days. These data suggest that infusion of marrow fibroblasts stimulates mobilization of ELC, which is associated with a reduction in otherwise progressive radiation-induced lung injury. We hypothesize that these two observations are related, specifically that circulating ELC contribute to increased angiogenesis, which facilitates endogenous lung repair.

  13. Arecoline-stimulated connective tissue growth factor production in human buccal mucosal fibroblasts: Modulation by curcumin.

    Science.gov (United States)

    Deng, Yi-Ting; Chen, Hsin-Ming; Cheng, Shih-Jung; Chiang, Chun-Pin; Kuo, Mark Yen-Ping

    2009-09-01

    Connective tissue growth factor (CTGF) is associated with the onset and progression of fibrosis in many human tissues. Areca nut (AN) chewing is the most important etiological factor in the pathogenesis of oral submucous fibrosis (OSF). We immunohistochemically examined the expression of CTGF protein in 20 cases of OSF and found positive CTGF staining in fibroblasts and endothelial cells in all cases. Western blot analysis showed that arecoline, a main alkaloid found in AN, stimulated CTGF synthesis in a dose- and time-dependent manner in buccal mucosal fibroblasts. Constitutive overexpression of CTGF during AN chewing may enhance the fibrotic activity in OSF and play a role in the pathogenesis of OSF. Pretreatment with NF-kappaB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580 and antioxidant N-acetyl-l-cysteine, but not ERK inhibitor PD98059, significantly reduced arecoline-induced CTGF synthesis. Furthermore, curcumin completely inhibited arecoline-induced CTGF synthesis and the inhibition is dose-dependent. These results indicated that arecoline-induced CTGF synthesis was mediated by ROS, NF-kappaB, JNK, P38 MAPK pathways and curcumin could be a useful agent in controlling OSF.

  14. Arecoline stimulated early growth response-1 production in human buccal fibroblasts: suppression by epigallocatechin-3-gallate.

    Science.gov (United States)

    Hsieh, Yu-Ping; Chen, Hsin-Ming; Chang, Jenny Zwei-Chieng; Chiang, Chun-Pin; Deng, Yi-Ting; Kuo, Mark Yen-Ping

    2015-04-01

    Early growth response-1 (Egr-1) protein plays an important role in many human fibrotic diseases. Areca nut chewing is the most important risk factor of oral submucous fibrosis (OSF). Egr-1 protein expression in OSF was examined using antibody to Egr-1. Arecoline-induced Egr-1 expression and its signaling pathways were assessed by Western blot analyses in human buccal mucosal fibroblasts (BMFs). Elevated Egr-1 staining was observed in epithelial cells, fibroblast, and inflammatory cells in 7 of 10 OSF cases. Arecoline, a main alkaloid found in the areca nut, stimulated Egr-1 synthesis in BMFs. Pretreatment with antioxidant N-acetyl-L-cysteine, c-Jun NH2-terminal kinase inhibitor SP600125, and extracellular signal-regulated kinase inhibitor PD98059 significantly reduced arecoline-induced Egr-1 synthesis. Epigallocatechin-3-gallate (EGCG) inhibited arecoline-induced Egr-1 synthesis and collagen gel contraction in a dose-responsive manner. Constitutive Egr-1 expression during areca nut chewing may play a role in the pathogenesis of OSF. EGCG could be a good candidate for prevention or treatment of OSF. © 2014 Wiley Periodicals, Inc.

  15. Quest for anti-inflammatory substances using IL-1β-stimulated gingival fibroblasts.

    Science.gov (United States)

    Ono, Manami; Kantoh, Kaori; Ueki, Junichi; Shimada, Aki; Wakabayashi, Hidetsugu; Matsuta, Tomohiko; Sakagami, Hiroshi; Kumada, Hidefumi; Hamada, Nobushiro; Kitajima, Madoka; Oizumi, Hiroshi; Oizumi, Takaaki

    2011-01-01

    We have previously reported that azulene-related compounds, and alkaline extract of Sasa senanensis Rehder potently inhibited nitric oxide (NO) production by lipopolysaccharide (LPS)-stimulated mouse macrophages. We investigated here whether they can inhibit pro-inflammatory cytokine production, by activated human gingival fibroblast (HGF). HGF was established from the periodontal tissues of extracted tooth. Viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Production of Prostaglandin E(2) (PGE(2)) and cytokines was determined by enzyme immunoassay, and enzyme-linked immunosorbent assay, respectively. Interleukin (IL)-1β did not inhibit, but rather slightly stimulated the growth of HGF cells. IL-1β stimulated the production of PGE(2), IL-6, IL-8 and monocyte chemotactic protein-1 very potently, but not that of nitric oxide and tumor necrosis factor-α. Native LPS and synthetic lipid A from E. coli and P. gingivalis was much less stimulatory. Dexamethasone, not indomethacin, was an efficient inhibitor of IL-8 production. Among five azulene-related compounds, benzo[b]cyclohepta[e][1,4]thiazine most potently inhibited the IL-8 production by HGF cells, as well as NO production by activated RAW264.7 cells. The alkaline extract of Sasa senanensis Rehder significantly inhibited IL-8 production, without affecting the cell viability. The present system may be applicable for use in the search for anti-gingivitis substances.

  16. Co-cultivation of pancreatic cancer cells with orthotopic tumor-derived fibroblasts: fibroblasts stimulate tumor cell invasion via HGF secretion whereas cancer cells exert a minor regulative effect on fibroblasts HGF production.

    Science.gov (United States)

    Qian, Li-Wu; Mizumoto, Kazuhiro; Maehara, Naoki; Ohuchida, Kenoki; Inadome, Naoki; Saimura, Michiyo; Nagai, Eishi; Matsumoto, Kunio; Nakamura, Toshikazu; Tanaka, Masao

    2003-02-10

    The intensive stromal reaction is one of characteristics of pancreatic exocrine carcinoma. The mutual interaction between pancreatic cancer cells and orthotopic tumor-derived fibroblasts have not been clarified yet. In this study, we sought to elucidate the mechanism underlying the tumor-stromal interaction with an in vitro coculture experimental system. Considerable strong c-Met expression was detected in seven out ten lines of human pancreatic carcinoma cells, as determined by Western blotting. For hepatocyte growth factor (HGF)-production, however, none or only trace amounts of HGF could be detected in those ten cell lines. Of the two lots of tumor-derived fibroblasts obtained from two pancreatic cancer patients, the fibroblasts capable to produce HGF could initiate an apparent invasion-stimulating response in strong c-Met-expressed Suit-2 and Panc-1 cells but not in faint expressed Mia PaCa-2 and BxPC-3 cells. A specialized HGF antagonist, NK4 would effectively inhibit the fibroblast-mediated invasive growth, thus proving the key role of the paracrine-fashioned HGF/c-Met pathway in the tumor-stromal interaction. On the other hand, the regulative action of cancer cells on HGF expression of fibroblasts was also investigated using direct or indirect coculture systems. For the fibroblasts that originally did not produce HGF, cancer cells failed to show any HGF-inductive effect. For the HGF-producing fibroblasts, despite of somewhat upregulation or downregulation in fibroblast HGF expression, the feedback regulation by studied pancreatic cancer cells in both coculture modes were relatively limited. This in vitro study sketched out the interaction between cancerous and stromal compartments with an emphasis on HGF/c-Met signal pathway, thus possibly helping to unveil the more complicated mutual modulation in vivo between pancreatic cancer and host mesenchymal tissues.

  17. Amentoflavone inhibits angiogenesis of endothelial cells and stimulates apoptosis in hypertrophic scar fibroblasts.

    Science.gov (United States)

    Zhang, Jinli; Liu, Zhihe; Cao, Wenjuan; Chen, Liying; Xiong, Xifeng; Qin, Shengnan; Zhang, Zhi; Li, Xiaojian; Hu, Chien-an A

    2014-08-01

    Amentoflavone (8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl) chromen-4-one; AF) is a biflavonoid derived from the extracts of Selaginella tamariscina. It has been shown that AF has diverse biological effects such as antitumour, etc. It is well known that high cell proliferation, viability, angiogenesis and low apoptosis are key factors in hypertrophic scar formation. In this study, we report that AF inhibited viability and stimulated apoptosis in hypertrophic scar fibroblasts (HSFBs). Incubation of HSFBs with AF showed its inhibitory effect on cell viability and the exhibition of a series of cellular changes that were consistent with apoptosis. By Western-blot analysis, our data indicated significant increases in the amounts of cleaved caspases 3, 8, 9 and Bax, several apoptotic promoters and a significant decrease in translationally controlled tumour protein (TCTP), an apoptotic inhibitor, in HSFBs treated with AF. Furthermore, AF showed significant inhibitions on the viability, migration and tube formation of endothelial cells, which are associated with angiogenesis. In conclusion, this study suggests that AF stimulates apoptosis in HSFBs and inhibits angiogenesis of endothelial cells. Therefore, AF is a promising molecule that can be used in hypertrophic scar treatment.

  18. Protective effect against oxygen reactive species and skin fibroblast stimulation of Couroupita guianensis leaf extracts.

    Science.gov (United States)

    Martínez, Ana; Conde, Enma; Moure, Andrés; Domínguez, Herminia; Estévez, Ramón J

    2012-01-01

    In this study, hydroalcoholic leaf extracts of Couroupita guianensis were examined for antioxidant activity, phytochemical and total phenolic composition, stimulation of human skin fibroblast (HSF) proliferation and UV-absorption. The radical scavenging capacity, reducing power and protection against joint oxidation of linoleic acid and β-carotene bleaching oxidation in emulsion were used to evaluate the antioxidant activity. The results of this study strongly indicate in vitro antioxidant activity, which may be due to the presence of a high total phenolic content. In order to identify active principles, the extracts were submitted to fractionation and the compounds isolated were the flavonoids 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (1), 7-hydroxy-5-methoxy-6,8-dimethylflavanone (2) and the phenolic acid 4-hydroxybenzoic acid (3). In addition, a high level of stimulation of HSF proliferation and significant absorption of UV radiation were also observed. The results suggest that the hydroalcoholic leaf extracts of C. guianensis have promising skin care properties.

  19. TRPM3 channel stimulated by pregnenolone sulphate in synovial fibroblasts and negatively coupled to hyaluronan

    Directory of Open Access Journals (Sweden)

    English Anne A

    2010-06-01

    Full Text Available Abstract Background Calcium-permeable channels are known to have roles in many mammalian cell types but the expression and contribution of such ion channels in synovial cells is mostly unknown. The objective of this study was to investigate the potential relevance of Transient Receptor Potential Melastatin 3 (TRPM3 channel to fibroblast-like synoviocytes (FLSs of patients with rheumatoid arthritis. Methods The study used RT-PCR and immunofluorescence to detect mRNA and protein. Intracellular calcium measurement detected channel activity in a FLS cell-line and primary cultures of FLSs from patients with rheumatoid arthritis. Enzyme-linked immunosorbent assays measured hyaluronan. Results Endogenous expression of TRPM3 was detected. Previously reported stimulators of TRPM3 sphingosine and pregnenolone sulphate evoked sustained elevation of intracellular calcium in FLSs. The FLS cell-line showed an initial transient response to sphingosine which may be explained by TRPV4 channels but was not observed in FLSs from patients. Blocking antibody targeted to TRPM3 inhibited sustained sphingosine and pregnenolone sulphate responses. Secretion of hyaluronan, which contributes adversely in rheumatoid arthritis, was suppressed by pregnenolone sulphate in FLSs from patients and the effect was blocked by anti-TRPM3 antibody. Conclusions The data suggest that FLSs of patients with rheumatoid arthritis express TRPM3-containing ion channels that couple negatively to hyaluronan secretion and can be stimulated by pharmacological concentrations of pregnenolone sulphate.

  20. Microarray profiling reveals suppressed interferon stimulated gene program in fibroblasts from scleroderma-associated interstitial lung disease

    Science.gov (United States)

    2013-01-01

    Background Interstitial lung disease is a major cause of morbidity and mortality in systemic sclerosis (SSc), with insufficiently effective treatment options. Progression of pulmonary fibrosis involves expanding populations of fibroblasts, and the accumulation of extracellular matrix proteins. Characterisation of SSc lung fibroblast gene expression profiles underlying the fibrotic cell phenotype could enable a better understanding of the processes leading to the progressive build-up of scar tissue in the lungs. In this study we evaluate the transcriptomes of fibroblasts isolated from SSc lung biopsies at the time of diagnosis, compared with those from control lungs. Methods We used Affymetrix oligonucleotide microarrays to compare the gene expression profile of pulmonary fibroblasts cultured from 8 patients with pulmonary fibrosis associated with SSc (SSc-ILD), with those from control lung tissue peripheral to resected cancer (n=10). Fibroblast cultures from 3 patients with idiopathic pulmonary fibrosis (IPF) were included as a further comparison. Genes differentially expressed were identified using two separate analysis programs following a set of pre-determined criteria: only genes significant in both analyses were considered. Microarray expression data was verified by qRT-PCR and/or western blot analysis. Results A total of 843 genes were identified as differentially expressed in pulmonary fibroblasts from SSc-ILD and/or IPF compared to control lung, with a large overlap in the expression profiles of both diseases. We observed increased expression of a TGF-β response signature including fibrosis associated genes and myofibroblast markers, with marked heterogeneity across samples. Strongly suppressed expression of interferon stimulated genes, including antiviral, chemokine, and MHC class 1 genes, was uniformly observed in fibrotic fibroblasts. This expression profile includes key regulators and mediators of the interferon response, such as STAT1, and CXCL10, and

  1. Wnt-4 expression is increased in fibroblasts after TGF-beta1 stimulation and during fetal and postnatal wound repair.

    Science.gov (United States)

    Colwell, Amy S; Krummel, Thomas M; Longaker, Michael T; Lorenz, H Peter

    2006-06-01

    Wnt-4 is a mitogen expressed during postnatal repair and scar formation; however, its expression profile during scarless repair is unknown. Transforming growth factor (TGF)-beta1 has high expression during healing with scar formation. Whether TGF-beta1 directly influences Wnt-4 expression in fetal or postnatal fibroblasts has not been examined. Primary fetal and postnatal mouse fibroblasts were stimulated with TGF-beta1 and Wnt-4 expression quantitated by real-time polymerase chain reaction. Fetal E17 and postnatal mouse excisional wounds were also analyzed for Wnt-4 expression by real-time polymerase chain reaction. In E17 fibroblasts after TGF-beta1 stimulation, Wnt-4 expression increased 4-fold at 1 hour (p stimulation, but peak expression was larger and relatively delayed, with a 17-fold increase at 12 hours (p fetal skin, Wnt-4 expression was 3.5-fold greater compared with 3-week-old mice (p fetal scarless and postnatal scarring mouse wound repair. The authors' data suggest that TGF-beta directly increases Wnt-4 expression in fetal and postnatal fibroblasts and that Wnt-4 is increased in both fetal and postnatal repair.

  2. Interleukin 1 stimulates hexose transport in fibroblasts by increasing the expression of glucose transporters.

    Science.gov (United States)

    Bird, T A; Davies, A; Baldwin, S A; Saklatvala, J

    1990-08-15

    Exposure of quiescent cultures of human gingival fibroblasts (HuGi) and porcine synovicocytes (PSF) to human recombinant interleukin 1 alpha or -beta (IL1 alpha and -beta) enhanced the rate of glycolysis as judged by increased lactate production. The cytokines also increased uptake of [3H]2-deoxyglucose (DG) in a time- and dose-dependent manner. Stimulation of DG uptake was first evident 6-8 h following addition of IL1 and was maximal by 24-30 h. IL1 alpha and -beta were equipotent. Half-maximal stimulation occurred at approximately 1 pM IL1; maximal stimulation (2.5-4.5-fold in HuGi, 3-7-fold in PSF) was obtained with approximately 80 pM IL1. The dose-response curves for lactate production and DG uptake were similar. Increased DG uptake was blocked by specific antisera to IL1 and by inhibitors of protein and RNA synthesis but not by indomethacin, an inhibitor of prostaglandin production. DG uptake was enhanced by IL1 in serum-starved cells in the presence of neutralizing anti-platelet-derived growth factor serum. The effect was therefore not secondary to prostaglandin or platelet-derived growth factor production. No increase in cell cycling was detected in IL1-treated cells under the experimental conditions. Kinetic analysis revealed that the Vmax for DG uptake was increased by IL1 (from 36 to 144 pmol/min/mg of cell protein), whereas the Km was unchanged. HuGi cells were pulse-labeled with [35S]methionine following exposure to IL1. Cell lysates were immunoprecipitated using a specific antiserum raised against human erythrocyte glucose transporter. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography of these immunoprecipitates revealed dose- and time-dependent increases in the net rate of glucose transporter synthesis which mirrored the changes in DG uptake.

  3. Hedgehog signaling is synergistically enhanced by nutritional deprivation and ligand stimulation in human fibroblasts of Gorlin syndrome.

    Science.gov (United States)

    Mizuochi, Hiromi; Fujii, Katsunori; Shiohama, Tadashi; Uchikawa, Hideki; Shimojo, Naoki

    2015-02-13

    Hedgehog signaling is a pivotal developmental pathway that comprises hedgehog, PTCH1, SMO, and GLI proteins. Mutations in PTCH1 are responsible for Gorlin syndrome, which is characterized by developmental defects and tumorigenicity. Although the hedgehog pathway has been investigated extensively in Drosophila and mice, its functional roles have not yet been determined in human cells. In order to elucidate the mechanism by which transduction of the hedgehog signal is regulated in human tissues, we employed human fibroblasts derived from three Gorlin syndrome patients and normal controls. We investigated GLI1 transcription, downstream of hedgehog signaling, to assess native signal transduction, and then treated fibroblasts with a recombinant human hedgehog protein with or without serum deprivation. We also examined the transcriptional levels of hedgehog-related genes under these conditions. The expression of GLI1 mRNA was significantly higher in Gorlin syndrome-derived fibroblasts than in control cells. Hedgehog stimulation and nutritional deprivation synergistically enhanced GLI1 transcription levels, and this was blocked more efficiently by vismodegib, a SMO inhibitor, than by the natural compound, cyclopamine. Messenger RNA profiling revealed the increased expression of Wnt signaling and morphogenetic molecules in these fibroblasts. These results indicated that the hedgehog stimulation and nutritional deprivation synergistically activated the hedgehog signaling pathway in Gorlin syndrome fibroblasts, and this was associated with increments in the transcription levels of hedgehog-related genes such as those involved in Wnt signaling. These fibroblasts may become a significant tool for predicting the efficacies of hedgehog molecular-targeted therapies such as vismodegib.

  4. Bifunctional bioceramics stimulating osteogenic differentiation of a gingival fibroblast and inhibiting plaque biofilm formation.

    Science.gov (United States)

    Shen, Ya; Wang, Zhejun; Wang, Jiao; Zhou, Yinghong; Chen, Hui; Wu, Chengtie; Haapasalo, Markus

    2016-04-01

    Gingival recession is a common clinical problem that results in esthetic deficiencies and poor plaque control and predominantly occurs in aged patients. In order to restore the cervical region, ideal biomaterials should possess the ability to stimulate proliferation and osteogenesis/cementogenesis of human gingival fibroblasts (HGF) and have a strong antibiofilm effect. The aim of the present study was to investigate the interactions of HGF and oral multispecies biofilms with Ca, Mg and Si-containing bredigite (BRT, Ca7MgSi4O16) bioceramics. BRT extract induced osteogenic/cementogenic differentiation of HGF and its inhibition of plaque biofilm formation were systematically studied. BRT extract in concentrations lower than <200 mg mL(-1) presented high biocompatibility to HGF cells in 3 days. Ion extracts from BRT also stimulated a series of bone-related gene and protein expressions in HGF cells. Furthermore, BRT extract significantly inhibited oral multispecies plaque biofilm growth on its surface and contributed to over 30% bacterial cell death without additional antibacterial agents in two weeks. A planktonic killing test showed that BRT suppressed 98% plaque bacterial growth compared to blank control in 3 days. The results also revealed that BRT extract has an osteostimulation effect on HGF. The suppression effect on plaque biofilms suggested that BRT might be used as a bioactive material for cervical restoration and that the synergistic effect of bioactive ions, such as Ca, Mg and Si ions, played an important role in the design and construction of bifunctional biomaterials in combination with tissue regeneration and antibiofilm activity.

  5. Stimulation of oral fibroblast chemokine receptors identifies CCR3 and CCR4 as potential wound healing targets.

    Science.gov (United States)

    Buskermolen, Jeroen K; Roffel, Sanne; Gibbs, Susan

    2017-11-01

    The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration, and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1, and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1, and XCL1) were used to study the activation of these receptors on gingiva fibroblasts. Twelve of these fourteen chemokines stimulated gingiva fibroblast migration (all except for CXCL8 and CXCL12). Five of the chemokines stimulated proliferation (CCL5/CCR3, CCL15/CCR3, CCL22/CCR4, CCL28/CCR3/CCR10, and XCL1/XCR1). Furthermore, CCL28/CCR3/CCR10 and CCL22/CCR4 stimulation increased IL-6 secretion and CCL28/CCR3/CCR10 together with CCL27/CCR10 upregulated HGF secretion. Moreover, TIMP-1 secretion was reduced by CCL15/CCR3. In conclusion, this in-vitro study identifies chemokine receptor-ligand pairs which may be used in future targeted wound healing strategies. In particular, we identified the chemokine receptors CCR3 and CCR4, and the mucosa specific chemokine CCL28, as having an predominant role in oral wound healing by increasing human gingiva fibroblast proliferation, migration, and the secretion of IL-6 and HGF and reducing the secretion of TIMP-1. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

  6. Stimulation of skin repair is dependent on fibroblast source and presence of extracellular matrix.

    NARCIS (Netherlands)

    Wang, H.; Pieper, J.S.; Schotel, R.; Blitterswijk, C.A. van; Lamme, E.N.

    2004-01-01

    In this study in vitro and in vivo functions were compared between cultured dermal equivalents produced with human fibroblasts isolated either from papillary dermis or adipose tissue of the same donors. Papillary dermal fibroblasts had a normal spindle cell shape; in contrast, adipose tissue fibrobl

  7. Stimulation of Skin Repair Is Dependent on Fibroblast Source and Presence of Extracellular Matrix

    NARCIS (Netherlands)

    Wang, Hong-Jun; Pieper, Jeroen; Schotel, Roka; Blitterswijk, van Clemens A.; Lamme, Evert N.

    2004-01-01

    In this study in vitro and in vivo functions were compared between cultured dermal equivalents produced with human fibroblasts isolated either from papillary dermis or adipose tissue of the same donors. Papillary dermal fibroblasts had a normal spindle cell shape; in contrast, adipose tissue fibrobl

  8. Stimulation of skin repair is dependent on fibroblast source and presence of extracellular matrix.

    NARCIS (Netherlands)

    Wang, H.; Pieper, J.S.; Schotel, R.; Blitterswijk, C.A. van; Lamme, E.N.

    2004-01-01

    In this study in vitro and in vivo functions were compared between cultured dermal equivalents produced with human fibroblasts isolated either from papillary dermis or adipose tissue of the same donors. Papillary dermal fibroblasts had a normal spindle cell shape; in contrast, adipose tissue

  9. Stimulation of skin repair is dependent on fibroblast source and presence of extracellular matrix

    NARCIS (Netherlands)

    Wang, Hongjun; Pieper, Jeroen; Schotel, Roka; van Blitterswijk, Clemens; Lamme, Evert N.

    2004-01-01

    In this study in vitro and in vivo functions were compared between cultured dermal equivalents produced with human fibroblasts isolated either from papillary dermis or adipose tissue of the same donors. Papillary dermal fibroblasts had a normal spindle cell shape; in contrast, adipose tissue

  10. Anti-inflammatory changes of gene expression by Artemisia iwayomogi in the LPS-stimulated human gingival fibroblast: microarray analysis.

    Science.gov (United States)

    Choi, Yeong-Gon; Yeo, Sujung; Kim, Sung-Hoon; Lim, Sabina

    2012-03-01

    The leaves and stems of Asteraceae Artemisia iwayomogi (Ai) for a long time have been known to inhibit inflammatory cytokine production and allergic reactions, and have been used to treat liver diseases. It needs to be elucidated in terms of global gene expression whether Ai has an influence as an anti-inflammatory agent on the cultured human gingival fibroblast stimulated with lipopolysaccharide (LPS). This study investigated the anti-inflammatory changes of the genes by Ai using the Affymetrix genechip human gene 1.0 ST array when the cultured human gingival fibroblast was treated with LPS. It was observed that the inflammation- and immune response-related genes were activated by LPS challenge in the cultured human gingival fibroblast. The array analysis showed that 65 of the 344 genes up-regulated by LPS stimulation, when compared to the control, were down-regulated by the Ai treatment. A number of inflammation- and immune response-related genes of the 65 genes were found. In addition, 78 of the 164 genes down-regulated by the LPS, when compared to the control, were up-regulated by the Ai treatment. The regulatory patterns of the representative genes were correlated with the real-time RT-PCR analysis. The Ai extract and its specific components, scopolin and scopoletin, significantly hindered the production of inflammatory mediators such as IL-6, TNF-α and nitrite in the LPS-challenged fibroblast. This study suggests that Ai can comprehensively inhibit the activation of the inflammation- and immune response-related genes and the inflammatory mediators in the human gingival fibroblast.

  11. CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Rong-hui, E-mail: fan_ronghuixa@163.com [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Zhu, Xiu-mei; Sun, Yao-wen [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Peng, Hui-zi [Department of Cosmetology Plastic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Wu, Hang-li; Gao, Wen-jie [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China)

    2016-07-08

    Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

  12. Cell density-dependent stimulation of PAI-1 and hyaluronan synthesis by TGF-β in orbital fibroblasts.

    Science.gov (United States)

    Galgoczi, Erika; Jeney, Florence; Gazdag, Annamaria; Erdei, Annamaria; Katko, Monika; Nagy, Domonkos M; Ujhelyi, Bernadett; Steiber, Zita; Gyory, Ferenc; Berta, Eszter; Nagy, Endre V

    2016-05-01

    During the course of Graves' orbitopathy (GO), orbital fibroblasts are exposed to factors that lead to proliferation and extracellular matrix (ECM) overproduction. Increased levels of tissue plasminogen activator inhibitor type 1 (PAI-1 (SERPINE1)) might promote the accumulation of ECM components. PAI-1 expression is regulated by cell density and various cytokines and growth factors including transforming growth factorβ(TGF-β). We examined the effects of increasing cell densities and TGF-β on orbital fibroblasts obtained from GO patients and controls. Responses were evaluated by the measurement of proliferation, PAI-1 expression, and ECM production. There was an inverse correlation between cell density and the per cell production of PAI-1. GO orbital, normal orbital, and dermal fibroblasts behaved similarly in this respect. Proliferation rate also declined with increasing cell densities. Hyaluronan (HA) production was constant throughout the cell densities tested in all cell lines. In both GO and normal orbital fibroblasts, but not in dermal fibroblasts, TGF-β stimulated PAI-1 production in a cell density-dependent manner, reaching up to a five-fold increase above baseline. This has been accompanied by increased HA secretion and pericellular HA levels at high cell densities. Increasing cell density is a negative regulator of proliferation and PAI-1 secretion both in normal and GO orbital fibroblasts; these negative regulatory effects are partially reversed in the presence of TGF-β. Cell density-dependent regulation of PAI-1 expression in the orbit, together with the local cytokine environment, may have a regulatory role in the turnover of the orbital ECM and may contribute to the expansion of orbital soft tissue in GO.

  13. Pregnancy Augments VEGF-Stimulated In Vitro Angiogenesis and Vasodilator (NO and H2S) Production in Human Uterine Artery Endothelial Cells.

    Science.gov (United States)

    Zhang, Hong-Hai; Chen, Jennifer C; Sheibani, Lili; Lechuga, Thomas J; Chen, Dong-Bao

    2017-07-01

    Augmented uterine artery (UA) production of vasodilators, including nitric oxide (NO) and hydrogen sulfide (H2S), has been implicated in pregnancy-associated and agonist-stimulated rise in uterine blood flow that is rate-limiting to pregnancy health. Developing a human UA endothelial cell (hUAEC) culture model from main UAs of nonpregnant (NP) and pregnant (P) women for testing a hypothesis that pregnancy augments endothelial NO and H2S production and endothelial reactivity to vascular endothelial growth factor (VEGF). Main UAs from NP and P women were used for developing hUAEC culture models. Comparisons were made between NP- and P-hUAECs in in vitro angiogenesis, activation of cell signaling, expression of endothelial NO synthase (eNOS) and H2S-producing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase, and NO/H2S production upon VEGF stimulation. NP- and P-hUAECs displayed a typical cobblestone-like shape in culture and acetylated low-density lipoprotein uptake, stained positively for endothelial and negatively for smooth muscle markers, maintained key signaling proteins during passage, and had statistically significant greater eNOS and CBS proteins in P- vs NP-hUAECs. Treatment with VEGF stimulated in vitro angiogenesis and eNOS protein and NO production only in P-hUEACs and more robust cell signaling in P- vs NP-hUAECs. VEGF stimulated CBS protein expression, accounting for VEGF-stimulated H2S production in hUAECs. Comparisons between NP- and P-hUAECs reveal that pregnancy augments VEGF-stimulated in vitro angiogenesis and NO/H2S production in hUAECs, showing that the newly established hUAEC model provides a critical in vitro tool for understanding human uterine hemodynamics.

  14. Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

  15. Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing.

    OpenAIRE

    Montesano, R; Orci, L.

    1988-01-01

    An important event during wound healing is the contraction of newly formed connective tissue (granulation tissue) by fibroblasts. The role of polypeptide growth factors in the process of wound contraction was investigated by analyzing the influence of transforming growth factor beta (TGF-beta), platelet-derived growth factor on the ability of fibroblasts to contract a collagen matrix in an in vitro system. TGF-beta, but not the other growth factors tested, markedly enhanced the ability of BHK...

  16. Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing.

    OpenAIRE

    Montesano, R; Orci, L

    1988-01-01

    An important event during wound healing is the contraction of newly formed connective tissue (granulation tissue) by fibroblasts. The role of polypeptide growth factors in the process of wound contraction was investigated by analyzing the influence of transforming growth factor beta (TGF-beta), platelet-derived growth factor on the ability of fibroblasts to contract a collagen matrix in an in vitro system. TGF-beta, but not the other growth factors tested, markedly enhanced the ability of BHK...

  17. A comparative study of antiestrogen action: temporal patterns of antagonism of estrogen stimulated uterine growth and effects on estrogen receptor levels.

    Science.gov (United States)

    Ferguson, E R; Katzenellenbogen, B S

    1977-05-01

    Studies were undertaken to ascertain the effects of structural modification of two well-known antiestrogens (CI-628 and U-11,100A) on their estrogenic and antiestrogenic potencies and temporal patterns of effectiveness in the immature rat uterus. Changes in the chemical structures of these anti-estrogens produce compounds with markedly different affinities for the uterine estrogen receptor as measured in an in vitro cell-free cytosol system; binding affinities relative to estradiol (100%) are: CI-628, 4%; CI-680, 34%; 94X1127 (94X),222%; U-11,100A (UA), 6%; and U-23,469 (U-23), 0.1%. Although all five antiestrogens (daily injections of 50 microng over three days) appear equally effective in stimulating 72 h uterine weight when given alone, or in blocking the estradiol-stimulated weight increase when given with estradiol, marked differences in their potencies are noted when the effects of the compounds are monitored beyond 24 h following a single injection. The compounds CI-628, CI-680 and UA (50 microng sc in saline), which have a methylated hydroxyl group (at the site analogous to the steroid position 3), show a prolonged maintenance of elevated levels of nuclear receptor (beyond 48 h) and elevated uterine weight (until 72 h); this correlates with a prolonged period of depressed cytoplasmic receptor levels (beyond 48 h) and prolonged uterine insensitivity to estrogen (beyond 36 h as monitored by 3 h wet weight response). In contrast, a single injection of 50 microng of 94X (having a free hydroxyl group) or U-23 (with a side chain and central ring different from UA) maintained nuclear receptor levels elevated for only 12 h (94X) or 36 h (U-23) and uterine weights declined after 36-48 h; cytoplasmic receptor levels remained depressed for only 12 h (94X) or 24 h (U-23) and then returned to control levels or above by 36 h. These latter compounds likewise evoked the shortest period of uterine insensitivity to estrogen (ineffective as antagonists by 36 h). Comparative

  18. CCL3 and CXCL12 production in vitro by dental pulp fibroblasts from permanent and deciduous teeth stimulated by Porphyromonas gingivalis LPS

    Directory of Open Access Journals (Sweden)

    Carla Renata Sipert

    2013-04-01

    Full Text Available Objective: The aim of this study was to compare the production of the chemokines CCL3 and CXCL12 by cultured dental pulp fibroblasts from permanent (PDPF and deciduous (DDPF teeth under stimulation by Porphyromonas gingivalis LPS (PgLPS. Material and Methods: Primary culture of fibroblasts from permanent (n=3 and deciduous (n=2 teeth were established using an explant technique. After the fourth passage, fibroblasts were stimulated by increasing concentrations of PgLPS (0 – 10 µg/mL at 1, 6 and 24 h. The cells were tested for viability through MTT assay, and production of the chemokines CCL3 and CXCL12 was determined through ELISA. Comparisons among samples were performed using One-way ANOVA for MTT assay and Two-way ANOVA for ELISA results. Results: Cell viability was not affected by the antigen after 24 h of stimulation. PgLPS induced the production of CCL3 by dental pulp fibroblasts at similar levels for both permanent and deciduous pulp fibroblasts. Production of CXCL12, however, was significantly higher for PDPF than DDPF at 1 and 6 h. PgLPS, in turn, downregulated the production of CXCL12 by PDPF but not by DDPF. Conclusion: These data suggest that dental pulp fibroblasts from permanent and deciduous teeth may present a differential behavior under PgLPS stimulation.

  19. Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.

    Directory of Open Access Journals (Sweden)

    Valentina Bizzarro

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we have evaluated whether Annexin A1 derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions. Using normal human skin fibroblasts WS1 in low glucose (LG or high glucose (HG we observed the enrichment of Annexin A1 protein at cell movement structures like lamellipodial extrusions and interestingly, a significant decrease in levels of the protein in HG conditions. The analysis of the translocation of Annexin A1 to cell membrane showed lower levels of Annexin A1 in both membrane pool and supernatants of WS1 cells treated with HG. Wound-healing assays using cell line transfected with Annexin A1 siRNAs indicated a slowing down in migration speed of cells suggesting that Annexin A1 has a role in the migration of WS1 cells. In order to analyze the role of extracellular Annexin A1 in cell migration, we have performed wound-healing assays using Ac2-26 showing that peptide was able to increase fibroblast cell migration in HG conditions. Experiments on the mobilization of intracellular calcium and analysis of p-ERK expression confirmed the activity of the FPR1 following stimulation with the peptide Ac2-26. A wound-healing assay on WS1 cells in the presence of the FPR agonist fMLP, of the FPR antagonist CsH and in the presence of Ac2-26 indicated that Annexin A1 influences fibroblast cell migration under HG conditions acting through FPR receptors whose expression was slightly increased in HG. In conclusion, these data demonstrate that (i Annexin A1 is involved in migration of WS1 cells, through interaction with FPRs; (ii N- terminal peptide of Annexin A1 Ac2-26 is able to stimulate direct migration of WS1 cells in high glucose treatment possibly due to the increased receptor expression observed in hyperglycemia conditions.

  20. Human ovarian neoplasm cell CD147 stimulates production and activation of matrix metalloproteinases in co-cultures with mouse fibroblasts

    Institute of Scientific and Technical Information of China (English)

    YANG Hong; ZOU Wei; XIN Xiao-yan

    2005-01-01

    Objective: To investigate the expression of CD147 on human ovarian neoplasm cell lines and its influence on production and activation of matrix metallproteinases(MMPs). Methods: The expression of CD147 on different human ovarian neoplasm cell lines was studied by western blotting. Co-culture was carried out to investigate the stimulative effect of the positive expression CD147 cell HO-8910 on the production of MMPs of fibroblast cell in vitro. Zymography and immune blotting were used to study the production and activity of positive MMPs, at the time, to explore the relation between CD147 and MMPs. Results: CD147 was positively presented in 2 ovarian neoplasm cell lines(HO-8910,3-AO), but in SKOV3, TC-1,NIN3T3 cell was negative. MMP-2 and MMP-9 were detected by HO-8910 cell line, mouse fibroblast cell and co-culture cells; but the expression in co-culture cell is obviously higher than individual cultures of each type alone.CD147 stimulated MMPs in dose-dependent manner. Conclusion: CD147 causes increased production and activation of MMP-2, MMP-9.CD147 is probably a indirect marker of some ovarian cancer cells with invasion and metastasis.

  1. Hypoxic regulation of plasminogen activator inhibitor-1 expression in human buccal mucosa fibroblasts stimulated with arecoline.

    Science.gov (United States)

    Tsai, Chung-Hung; Lee, Shiuan-Shinn; Chang, Yu-Chao

    2015-10-01

    Oral submucous fibrosis (OSF) is regarded as a pre-cancerous condition with fibrosis in oral subepithelial connective tissue. Hypoxia-inducible factor (HIF)-1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1α expression in normal buccal mucosa tissues and OSF specimens and further explore the potential mechanisms that may lead to the induction of HIF-1α expression. Twenty-five OSF specimens and six normal buccal mucosa were examined by immunohistochemistry. The expression of HIF-1α from fibroblasts cultured from OSF and normal buccal mucosa was measured by Western blot. Arecoline, a major areca nut alkaloid, was challenged to normal buccal mucosa fibroblasts (BMFs) to elucidate whether HIF-1α expression could affect by arecoline. In addition, the effects of arecoline on plasminogen activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia. HIF-1α expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, epithelial cells, and inflammatory cells. Fibroblasts derived from OSF were found to exhibit higher HIF-1α protein expression than BMFs (P Arecoline was found to upregulate HIF-1α protein in a dose-dependent manner (P arecoline-induced PAI-1 protein expression than normoxic conditions (P < 0.05). These results suggest that HIF-1α expression is significantly upregulated in OSF tissues from areca quid chewers, implying a potential role as a biomarker for local tissue hypoxia. The activation of HIF-1α may promote fibrogenesis by an increase of PAI-1 expression and a subsequent elevation of extracellular matrix production in oral submucosa leading to fibrosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Uterine Cancer

    Science.gov (United States)

    ... is pregnant. There are different types of uterine cancer. The most common type starts in the endometrium, ... the uterus. This type is also called endometrial cancer. The symptoms of uterine cancer include Abnormal vaginal ...

  3. The upregulation of heat shock protein 47 expression in human buccal fibroblasts stimulated with arecoline.

    Science.gov (United States)

    Yang, Shun-Fa; Tsai, Chung-Hung; Chang, Yu-Chao

    2008-04-01

    Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare HSP47 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further to explore the potential mechanisms that may lead to induce HSP47 expression. The mRNA levels of HSP47 from fibroblasts cultured from 20 OSF and 10 normal buccal mucosal fibroblasts (BMFs) were evaluated by reverse transcription polymerase chain reaction. The effect of arecoline, the major areca nut alkaloid, was added to explore the potential mechanisms that may lead to induce HSP47 expression. Furthermore, mitogen-activated protein kinase kinase (MEK) inhibitor U0126, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, p38 inhibitor SB203580, cyclo-oxygenase-2 (COX-2) inhibitor NS-398, and glutathione precursor N-acetyl-l-cysteine were added to find the possible mechanisms. OSF demonstrated significantly higher HSP47 mRNA expression than BMFs (P Arecoline was also found to elevate HSP47 mRNA expression in a dose-dependent manner (P arecoline when compared with control (P arecoline-induced HSP47 mRNA expression (P arecoline in fibroblasts may be mediated by MEK, PI3K, and COX-2 signal transduction pathways.

  4. Cysteine-rich protein 61 (CCN1) domain-specific stimulation of matrix metalloproteinase-1 expression through αVβ3 integrin in human skin fibroblasts.

    Science.gov (United States)

    Qin, Zhaoping; Fisher, Gary J; Quan, Taihao

    2013-04-26

    Human skin largely comprises collagenous extracellular matrix. The hallmark of skin aging is fragmentation of collagen fibrils. Matrix metalloproteinases (MMPs) are largely responsible for collagen degradation. MMP-1, principally derived from dermal fibroblasts, is the major protease capable of initiating degradation of native fibrillar collagens. Presently, we report that CCN1, a secreted and extracellular matrix-associated protein, is elevated in aged human skin dermal fibroblasts in vivo and stimulates MMP-1 expression through functional interaction with αVβ3 integrin in human dermal fibroblasts. CCN1 contains four conserved structural domains. Our results indicate that the three N-terminal domains (IGFBP, VWC, and TSP1), but not the C-terminal CT domain, are required for CCN1 to stimulate MMP-1 expression. This stimulation is dependent on interaction between the active structural domains and αVβ3 integrin. The interaction of VWC domain with integrin αVβ3 is necessary and requires functional cooperation with adjacent IGFBP and TSP1 domains to stimulate MMP-1 expression. Finally, induction of MMP-1 expression in dermal fibroblasts by CCN1 N-terminal domains resulted in fragmentation of type I collagen fibrils in a three-dimensional collagen lattice model. These data suggest that domain-specific interactions of CCN1 with αVβ3 integrin contribute to human skin aging by stimulating MMP-1-mediated collagen fibril fragmentation.

  5. Regulation of hypoxia-inducible factor-1α in human buccal mucosal fibroblasts stimulated with arecoline

    Directory of Open Access Journals (Sweden)

    Yung-Chuan Ho

    2017-06-01

    Full Text Available Hypoxia-inducible factor (HIF-1α is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare HIF-1α expression from fibroblasts derived from human normal buccal mucosa and oral submucous fibrosis (OSF specimens and further to explore the potential mechanisms that may lead to induce HIF-1α expression. OSF buccal mucosal fibroblasts (BMFs demonstrated significantly higher HIF-1α mRNA expression than normal BMFs (p<0.005. Arecoline, the major areca nut alkaloid, was also found to elevate HIF-1α mRNA expression in a dose-dependent manner (p<0.05. Moreover, arecoline-induced HIF-1α expression was downregulated by mitogen-activated protein kinase inhibitor U0126, phosphatidylinositol 3-kinase inhibitor LY294002, p38 inhibitor SB203580, cyclooxygenase-2 inhibitor NS-398, and glutathione precursor N-acetyl-L-cysteine (p<0.05. Taken together, hypoxia plays an important role in the pathogenesis of areca quid chewing-associated OSF. These pharmacological agents may be further used as chemoprevention agents for OSF.

  6. Boron nitride nanotube-mediated stimulation modulates F/G-actin ratio and mechanical properties of human dermal fibroblasts

    Science.gov (United States)

    Ricotti, Leonardo; das Neves, Ricardo Pires; Ciofani, Gianni; Canale, Claudio; Nitti, Simone; Mattoli, Virgilio; Mazzolai, Barbara; Ferreira, Lino; Menciassi, Arianna

    2014-02-01

    F/G-actin ratio modulation is known to have an important role in many cell functions and in the regulation of specific cell behaviors. Several attempts have been made in the latest decades to finely control actin production and polymerization, in order to promote certain cell responses. In this paper we demonstrate the possibility of modulating F/G-actin ratio and mechanical properties of normal human dermal fibroblasts by using boron nitride nanotubes dispersed in the culture medium and by stimulating them with ultrasound transducers. Increasing concentrations of nanotubes were tested with the cells, without any evidence of cytotoxicity up to 10 μg/ml concentration of nanoparticles. Cells treated with nanoparticles and ultrasound stimulation showed a significantly higher F/G-actin ratio in comparison with the controls, as well as a higher Young's modulus. Assessment of Cdc42 activity revealed that actin nucleation/polymerization pathways, involving Rho GTPases, are probably influenced by nanotube-mediated stimulation, but they do not play a primary role in the significant increase of F/G-actin ratio of treated cells, such effect being mainly due to actin overexpression.

  7. Regulation of protease-activated receptor-1 expression in human buccal fibroblasts stimulated with arecoline.

    Science.gov (United States)

    Tsai, Chung-Hung; Lee, Shiuan-Shinn; Huang, Fu-Mei; Chang, Yu-Chao

    2013-09-01

    The purpose of this study was to compare the major thrombin receptor protease-activated receptor-1 (PAR-1) expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanisms that may lead to induce PAR-1 expression. Thirty OSF and 10 normal buccal mucosa specimens were examined by immunohistochemistry. Buccal mucosal fibroblasts (BMFs) were challenged with arecoline by using Western blot analysis. N-acetyl-L-cysteine (NAC), LY294002, herbimycin A, NS-398, and PD98059 were added to find the possible regulatory mechanisms. PAR-1 expression was significantly higher in OSF specimens (p Arecoline was found to elevate PAR-1 expression in a dose-dependent and time-dependent manner (p arecoline-induced PAR-1 expression (p Arecoline-induced PAR-1 expression was downregulated by NAC, LY294002, herbimycin A, NS398, and PD98059. Copyright © 2012 Wiley Periodicals, Inc.

  8. Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression.

    Science.gov (United States)

    Lechuga, Thomas J; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R; Rosenfeld, Charles R; Chen, Dong-bao

    2015-06-01

    Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health.

  9. PPAR-gamma ligands modulate effects of LPS in stimulated rat synovial fibroblasts.

    Science.gov (United States)

    Simonin, Marie-Agnès; Bordji, Karim; Boyault, Sandrine; Bianchi, Arnaud; Gouze, Elvire; Bécuwe, Philippe; Dauça, Michel; Netter, Patrick; Terlain, Bernard

    2002-01-01

    This work demonstrated the constitutive expression of peroxisome proliferator-activated receptor (PPAR)-gamma and PPAR-alpha in rat synovial fibroblasts at both mRNA and protein levels. A decrease in PPAR-gamma expression induced by 10 microg/ml lipopolysaccharide (LPS) was observed, whereas PPAR-alpha mRNA expression was not modified. 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) dose-dependently decreased LPS-induced cyclooxygenase (COX)-2 (-80%) and inducible nitric oxide synthase (iNOS) mRNA expression (-80%), whereas troglitazone (10 microM) only inhibited iNOS mRNA expression (-50%). 15d-PGJ(2) decreased LPS-induced interleukin (IL)-1 beta (-25%) and tumor necrosis factor (TNF)-alpha (-40%) expression. Interestingly, troglitazone strongly decreased TNF-alpha expression (-50%) but had no significant effect on IL-1 beta expression. 15d-PGJ(2) was able to inhibit DNA-binding activity of both nuclear factor (NF)-kappa B and AP-1. Troglitazone had no effect on NF-kappa B activation and was shown to increase LPS-induced AP-1 activation. 15d-PGJ(2) and troglitazone modulated the expression of LPS-induced iNOS, COX-2, and proinflammatory cytokines differently. Indeed, troglitazone seems to specifically target TNF-alpha and iNOS pathways. These results offer new insights in regard to the anti-inflammatory potential of the PPAR-gamma ligands and underline different mechanisms of action of 15d-PGJ(2) and troglitazone in synovial fibroblasts.

  10. Human periodontal ligament fibroblasts stimulated by nanocrystalline hydroxyapatite paste or enamel matrix derivative. An in vitro assessment of PDL attachment, migration, and proliferation

    NARCIS (Netherlands)

    Kasaj, A.; Willershausen, B.; Junker, R.; Stratul, S.I.; Schmidt, M.

    2012-01-01

    We determined the effects of soluble or coated nanocrystalline hydroxyapatite paste (nano-HA) and enamel matrix derivative (EMD) on proliferation, adhesion, and migration of periodontal ligament fibroblasts (PDLs). Cultured PDLs were stimulated with nano-HA paste or EMD in a soluble form or were

  11. Petroleum ether extract of Cissus quadrangularis (LINN stimulates the growth of fetal bone during intra uterine developmental period: a morphometric analysis

    Directory of Open Access Journals (Sweden)

    Bhagath Kumar Potu

    2008-01-01

    Full Text Available OBJECTIVE: The aim of the present study was to analyze the effect Cissus quadrangularis plant petroleum ether extract on the development of long bones during the intra-uterine developmental stage in rats. METHODS: Pregnant rats (n=12 were randomly assigned into either a control group (n=6 or a Cissus quadrangularis treatment (n=6 group. Pregnant rats in the Cissus quadrangularis group were treated with Cissus quadrangularis petroleum ether extract at a dose of 500 mg/kg body weight from gestation day 9 until delivery. The animals in the control group received an equal volume of saline. Newborn pups were collected from both groups for alizarin red S - alcian blue staining to differentiate ossified and unossified cartilage. The ossified cartilage (bone was morphometrically analyzed using Scion image software. RESULTS: Morphometric analysis revealed that the percentage of the total length of ossified cartilage (bone in pups born to treated dams was significantly higher (P<0.001- -0.0001 than that of the control group. CONCLUSION: The results of the present study suggest that maternal administration of Cissus quadrangularis petroleum ether extract during pregnancy can stimulate the development of fetal bone growth during the intra-uterine developmental period.

  12. Regulation of Interferon-stimulated Gene (ISG)12, ISG15, and MX1 and MX2 by Conceptus Interferons (IFNTs) in Bovine Uterine Epithelial Cells.

    Science.gov (United States)

    Kim, Min-Su; Min, Kwan-Sik; Imakawa, Kazuhiko

    2013-06-01

    Various endometrial genes in ruminant ungulates are regulated by conceptus interferon tau (IFNT). However, the effect of each IFNT isoform has not been carefully evaluated. In this study, the effects of 2 IFNT isoforms, paralogs found in utero, and interferon alpha (IFNA) on uterine epithelial and Mardin-Darby bovine kidney (MDBK) cells were evaluated. Expression vectors of the bovine interferon (bIFNT) genes bIFNT1, bIFNTc1, and bIFNA were constructed, and recombinant bIFNs (rbIFNs) were produced by 293 cells. Bovine uterine epithelial or MDBK cells were cultured in the presence or absence of increasing concentrations of each rbIFN for 24, 48, or 72 h. Transcript levels of the IFN-stimulated genes (ISGs) ISG12, ISG15, MX1, and MX2 were analyzed using quantitative reverse transcription-polymerase chain reaction. These messenger RNAs were up-regulated by rbIFN in a time- and concentration-dependent manner. In the epithelial cells, the ISG12 transcript level increased at 48 h after rbIFN treatment but slightly decreased at 72 h, whereas the transcript level of ISG15 increased at 24 h and was maintained through 72 h. Expressions of MX1 and MX2 increased at 72 h after rbIFN treatment. MX1 expression increased in all treatment groups, but MX2 increased only by bIFNTc1. In MDBK cells, the expression of ISG12 was increased by bIFNT1 and bIFNTc1 after 24 and 72 h; however, it was unchanged by rbIFNA. ISG15 increased following the same pattern as that seen in uterine epithelial cells, and MX1 showed a similar expression pattern. MX2 expression was increased by bIFNTc1 treatment in uterine epithelial cells, and its expression was increased by both bIFNT1 and bIFNTc1 in MDBK cells. These results show that epithelial and MDBK cell responses to IFNs differ, suggesting that IFNs possess common functions, but may have acquired different functions following gene duplication.

  13. Oral phosphorus supplementation secondarily increases circulating fibroblast growth factor 23 levels at least partially via stimulation of parathyroid hormone secretion.

    Science.gov (United States)

    Takasugi, Satoshi; Akutsu, Miho; Nagata, Masashi

    2014-01-01

    Oral phosphorus supplementation stimulates fibroblast growth factor 23 (FGF23) secretion; however, the underlying mechanism remains unclear. The aim of this study was to investigate the involvement of parathyroid hormone (PTH) in increased plasma FGF23 levels after oral phosphorus supplementation in rats. Rats received single dose of phosphate with concomitant subcutaneous injection of saline or human PTH (1-34) after treatment with cinacalcet or its vehicle. Cinacalcet is a drug that acts as an allosteric activator of the calcium-sensing receptor and reduces PTH secretion. Plasma phosphorus and PTH levels significantly increased 1 h after oral phosphorus administration and returned to basal levels within 3 h, while plasma FGF23 levels did not change up to 2 h post-treatment, but rather significantly increased at 3 h after administration and maintained higher levels for at least 6 h compared with the 0 time point. Plasma PTH and FGF23 levels were significantly lower in the cinacalcet-treated rats than in the vehicle-treated rats. Plasma phosphorus levels were significantly higher in the cinacalcet-treated rats than in the vehicle-treated rats at 2, 3, 4, and 6 h after oral phosphorus administration. Furthermore, rats treated with cinacalcet+human PTH (1-34) showed transiently but significantly higher plasma FGF23 levels at 3 h after oral phosphorus administration compared with cinacalcet-treated rats. These results suggest that oral phosphorus supplementation secondarily increases circulating FGF23 levels at least partially by stimulation of PTH secretion.

  14. ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation

    DEFF Research Database (Denmark)

    Hinsby, Anders M; Lundfald, Line; Ditlevsen, Dorte K;

    2004-01-01

    by two principal routes of signaling: NCAM/Fyn and NCAM/fibroblast growth factor receptor (FGFR), respectively. Previous studies have shown that activation of mitogen-activated protein kinases is a pivotal point of convergence in NCAM signaling, but the mechanisms behind this activation are not clear....... Here, we investigated the involvement of adaptor proteins in NCAM and fibroblast growth factor 2 (FGF2)-mediated neurite outgrowth in the PC12-E2 cell line. We found that both FGFR substrate-2 and Grb2 play important roles in NCAM as well as in FGF2-stimulated events. In contrast, the docking protein...... ShcA was pivotal to neurite outgrowth induced by NCAM, but not by FGF2, in PC12 cells. Moreover, in rat cerebellar granule neurons, phosphorylation of ShcA was stimulated by an NCAM mimicking peptide, but not by FGF2. This activation was blocked by inhibitors of both FGFR and Fyn, indicating that NCAM...

  15. Delivery of basic fibroblast growth factors from heparinized decellularized adipose tissue stimulates potent de novo adipogenesis.

    Science.gov (United States)

    Lu, Qiqi; Li, Mingming; Zou, Yu; Cao, Tong

    2014-01-28

    Scaffolds based on decellularized adipose tissue (DAT) are gaining popularity in adipose tissue engineering due to their high biocompatibility and adipogenic inductive property. However, previous studies involving DAT-derived scaffolds have not fully revealed their potentials for in vivo adipose tissue construction. With the aim of developing a more efficient adipose tissue engineering technique based on DAT, in this study, we investigated the in vivo adipogenic potential of a basic fibroblast growth factor (bFGF) delivery system based on heparinized DAT (Hep-DAT). To generate this system, heparins were cross-linked to mouse DATs by using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide and N-Hydroxysuccinimide. The bFGF-binding Hep-DATs were first tested for controlled release ability in vitro and then transplanted subcutaneously. Highly vascularized adipose tissues were formed 6weeks after transplantation. Histology and gene expression analysis revealed that majority of the Hep-DAT scaffolds were infiltrated with host-derived adipose tissues that possessed similar adipogenic and inflammatory gene expression as endogenous adipose tissues. Additionally, strong de novo adipogenesis could also be induced when bFGF-binding Hep-DATs were thoroughly minced and injected subcutaneously. In conclusion, our study demonstrated that bFGF-binding Hep-DAT could be an efficient, biocompatible and injectable adipogenic system for in vivo adipose tissue engineering.

  16. Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts

    Directory of Open Access Journals (Sweden)

    Olsen Charlotta J

    2010-08-01

    Full Text Available Abstract Introduction Tumour phenotype is regulated in a complex fashion as a result of interactions between malignant cells and the tumour stroma. Fibroblasts are the most abundant and perhaps most active part of the tumour stroma. A better understanding of the changes that occur in fibroblasts in response to the presence of malignant cells may lead to the development of new strategies for cancer treatment. We explored the effects of fibroblasts on the growth and invasion of mammary carcinoma tumour cells in vitro and in vivo. Methods In order to analyse secreted factors that affect invasive abilities of breast cancer cells we co-cultured human mammary fibroblasts (HMF3s and cancer cells (MCF7S1 in three-dimensional (3D growth conditions devoid of heterogeneous cell-cell contact. To study the possible influence of fibroblasts on MCF7S1 cancer cell growth in vivo we co-injected HMF3s and MCF7S1 cells in Balb/c nu/nu mice. Results In 3D co-culture both HMF3s and MCF7S1 cells demonstrated enhanced invasion into a Matrigel matrix. This was correlated with enhanced expression of the metastasis promoting S100A4 protein in fibroblasts, stimulation of the matrix metalloproteinase (MMP-2 activity, and enhanced secretion of a range of different cytokines. Orthotopic injection of oestrogen-dependent MCF7S1 cancer cells together with fibroblasts showed stimulation of tumour growth in mice without an external oestrogen supply. The resulting tumours were characterized by increased development of extracellular matrix, as well as an increase of murine S100A4 concentration and activity of MMP-2 in the tumour interstitial fluid. Conclusion Stimulation of the invasive phenotype of tumour cells in 3D co-cultures with fibroblasts could be correlated with increased production of S100A4 and MMP-2. We propose that enhanced development of mouse host-derived tumour stroma in a MCF7S1 co-injection xenograft model leads to oestrogen independency and is triggered by the

  17. Secretion by stimulated murine macrophages of a heparin-binding fibroblast growth activity, distinct from basic FGE and IL-1

    Energy Technology Data Exchange (ETDEWEB)

    Rappolee, D.A.; Banda, M.J.; Werb, Z.

    1986-03-01

    Wound healing requires granulation and formation of neovascularization tissue. These two events require increases in fibroblasts, vascular endothelial, and smooth muscle cells. Macrophages may produce several growth factors which participate in these would healing events. To test this hypothesis they have partially purified a fibroblast growth promoting activity from a murine macrophage cell line (P388 Dl). The activity causes growth in Balb/c and Swiss 3T3 cells as measured by thymidine uptake, nuclear labeling and increase in cell number. PDGF, Basic FGF, and EGF are also mitogenic by thymidine uptake, but purified human IL-1 and recombinant murine IL-1 are not. The activity is pH 2.5-, freeze/thaw-, and dialysis/lyphilyzation-stable. The activity elutes from heparin-Sepharose at 2.0M, but not 0.15m, 0.5M, or 3.0M NaCl. Basic FGF elutes from the same heparin-Sepharose batch at 3.0M, but not at the other three NaCl concentrations. The growth activity is secreted by viable murine macrophage line cells (P388D1, WEHI-3, RAW 264.7) at a 48 hour peak after activating (LPS) or phagocytic stimuli. Unstimulated P388D1 caused growth 1.7 times control whereas stimulation increases the growth 5.1 to 7.1 times control. The optimal activity concentration fails to complement insulin in an assay in which optimal basic FGF concentration complements insulin. These data suggest that the activity may contain a progression factor.

  18. L-arginine stimulates fibroblast proliferation through the GPRC6A-ERK1/2 and PI3K/Akt pathway.

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    Takashi Fujiwara

    Full Text Available L-arginine is considered a conditionally essential amino acid and has been shown to enhance wound healing. However, the molecular mechanisms through which arginine stimulates cutaneous wound repair remain unknown. Here, we evaluated the effects of arginine supplementation on fibroblast proliferation, which is a key process required for new tissue formation. We also sought to elucidate the signaling pathways involved in mediating the effects of arginine on fibroblasts by evaluation of extracellular signal-related kinase (ERK 1/2 activation, which is important for cell growth, survival, and differentiation. Our data demonstrated that addition of 6 mM arginine significantly enhanced fibroblast proliferation, while arginine deprivation increased apoptosis, as observed by enhanced DNA fragmentation. In vitro kinase assays demonstrated that arginine supplementation activated ERK1/2, Akt, PKA and its downstream target, cAMP response element binding protein (CREB. Moreover, knockdown of GPRC6A using siRNA blocked fibroblast proliferation and decreased phosphorylation of ERK1/2, Akt and CREB. The present experiments demonstrated a critical role for the GPRC6A-ERK1/2 and PI3K/Akt signaling pathway in arginine-mediated fibroblast survival. Our findings provide novel mechanistic insights into the positive effects of arginine on wound healing.

  19. Involvement of Ovarian Estradiol Biosynthesis and Pituitary FSH Expression in the Mechanism of Human Chorionic Gonadotropin Stimulation of Uterine Growth in Immature Female Rats

    Directory of Open Access Journals (Sweden)

    Sandrine Rafert

    2016-01-01

    Full Text Available In a previous work, we showed that human Chorionic Gonadotropin (hCG alone is able to stimulate uterine ponderal growth in immature female rats. In the present paper, we provide new information indicating that a single 100 ng hCG injection increased ovarian androgen availability and aromatase activity. These changes are consistent with an increase in ovarian estradiol secretion. Ovarian activin βA and activin βB subunit RNAs expression were also increased following hCG injection. Most interestingly, this treatment also led to an increase in FSHβ subunit mRNA expression in the pituitary, which might be due to hCG-stimulated ovarian activin secretion. We have not been able so far to follow the kinetics of the plasma concentrations of activin and FSH in hCG-treated animals compared to control animals. This has to be explored in the future to provide a more complete assessment of our model.

  20. The effect of Centella asiatica, vitamins, glycolic acid and their mixtures preparations in stimulating collagen and fibronectin synthesis in cultured human skin fibroblast.

    Science.gov (United States)

    Hashim, Puziah

    2014-03-01

    Centella asiatica (Linn.) Urban is well known in promoting wound healing and provides significant benefits in skin care and therapeutic products formulation. Glycolic acid and vitamins also play a role in the enhancement of collagen and fibronectin synthesis. Here, we evaluate the specific effect of Centella asiatica (CA), vitamins, glycolic acid and their mixture preparations to stimulate collagen and fibronectin synthesis in cultured human fibroblast cells. The fibroblast cells are incubated with CA, glycolic acid, vitamins and their mixture preparations for 48 h. The cell lysates were analyzed for protein content and collagen synthesis by direct binding enzyme immunoassay. The fibronectin of the cultured supernatant was measured by sandwich enzyme immunoassay. The results showed that CA, glycolic acid, vitamins A, E and C significantly stimulate collagen and fibronectin synthesis in the fibroblast. Addition of glycolic acid and vitamins to CA further increased the levels of collagen and fibronectin synthesis to 8.55 and 23.75 μg/100 μg, respectively. CA, glycolic acid, vitamins A, E, and C, and their mixtures demonstrated stimulatory effect on both extra-cellular matrix synthesis of collagen and fibronectin in in vitro studies on human foreskin fibroblasts, which is beneficial to skin care and therapeutic products formulation.

  1. Uterine Fibroids

    Science.gov (United States)

    ... permits the doctor to see fibroids inside the uterine cavity. Hysterosalpingography is a special X-ray test. It ... used to remove fibroids that protrude into the cavity of the uterus. A resectoscope is inserted through the hysteroscope. The ...

  2. Uterine Prolapse

    Science.gov (United States)

    ... Lose weight if you're overweight or obese. Kegel exercises Kegel exercises strengthen your pelvic floor muscles, which support ... from symptoms associated with uterine prolapse. To perform Kegel exercises, follow these steps: Tighten (contract) your pelvic ...

  3. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca.

    Directory of Open Access Journals (Sweden)

    Jun-Jie Wang

    Full Text Available It has been widely known that the giant panda (Ailuropoda melanoleuca is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF, a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

  4. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    Science.gov (United States)

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

  5. Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's - derived fibroblasts

    Directory of Open Access Journals (Sweden)

    Johnson Sandra

    2011-05-01

    Full Text Available Abstract Background Myofibroblasts, a derived subset of fibroblasts especially important in scar formation and wound contraction, have been found at elevated levels in affected Dupuytren's tissues. Transformation of fibroblasts to myofibroblasts is characterized by expression of alpha- smooth muscle actin (α-SMA and increased production of extracellular matrix (ECM components, both events of relevance to connective tissue remodeling. We propose that increasing the activation of the cyclic AMP (cAMP/protein kinase A signaling pathway will inhibit transforming growth factor-beta1 (TGF-β1-induced ECM synthesis and myofibroblast formation and may provide a means to blunt fibrosis. Methods Fibroblasts derived from areas of Dupuytren's contracture cord (DC, from adjacent and phenotypically normal palmar fascia (PF, and from palmar fascia from patients undergoing carpal tunnel release (CTR; CT were treated with TGF-β1 (2 ng/ml and/or forskolin (10 μM (a known stimulator of cAMP. Total RNA and protein extracted was subjected to real time RT-PCR and Western blot analysis. Results The basal mRNA expression levels of fibronectin- extra domain A (FN1-EDA, type I (COL1A2 and type III collagen (COL3A1, and connective tissue growth factor (CTGF were all significantly increased in DC- and in PF-derived cells compared to CT-derived fibroblasts. The TGF-β1 stimulation of α-SMA, CTGF, COL1A2 and COL3A1 was greatly inhibited by concomitant treatment with forskolin, especially in DC-derived cells. In contrast, TGF-β1 stimulation of FN1-EDA showed similar levels of reduction with the addition of forskolin in all three cell types. Conclusion In sum, increasing cAMP levels show potential to inhibit the formation of myofibroblasts and accumulation of ECM components. Molecular agents that increase cAMP may therefore prove useful in mitigating DC progression or recurrence.

  6. The newly discovered cytokine IL-34 is expressed in gingival fibroblasts, shows enhanced expression by pro-inflammatory cytokines, and stimulates osteoclast differentiation.

    Directory of Open Access Journals (Sweden)

    Elisabeth A Boström

    Full Text Available BACKGROUND: Interleukin-34 (IL-34 is a recently discovered cytokine functionally overlapping macrophage colony stimulating factor (M-CSF, a mediator of inflammation and osteoclastogenesis in bone-degenerative diseases such as rheumatoid arthritis. The objective of this study was to assess the expression of IL-34 in human gingival fibroblasts and investigate if the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α and Interleukin-1Β (IL-1β modulate its expression, and moreover if IL-34 could contribute to recruitment of bone-resorbing osteoclasts. METHODS: IL-34 expression was evaluated in gingival fibroblasts by real time PCR following stimulation by TNF-α, IL-1β, and treatment with inhibitors of intracellular pathways. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP staining of bone marrow macrophages treated with IL-34 or M-CSF in addition to receptor activator of nuclear factor kappa-B ligand (RANKL. RESULTS: IL-34 was expressed in gingival fibroblasts. The expression was enhanced by TNF-α and IL-1β, regulated by the transcription factor nuclear factor kappa B (NF-κΒ and activation of c-Jun N-terminal kinase (JNK. Further, IL-34 supports RANKL-induced osteoclastogensis of bone marrow macrophages, independently of M-CSF. SUMMARY: In conclusion, this study shows for the first time IL-34 expression in human gingival fibroblasts, stimulated by TNF-α and IL-1β, key mediators of periodontal inflammation. Furthermore, IL-34 can be substituted for M-CSF in RANKL-induced osteoclastogenesis. IL-34 may contribute to inflammation and osteoclastogenesis in bone-degenerative diseases such as periodontitis.

  7. Platelet-rich plasma stimulates human dermal fibroblast proliferation via a Ras-dependent extracellular signal-regulated kinase 1/2 pathway.

    Science.gov (United States)

    Hara, Tomoya; Kakudo, Natsuko; Morimoto, Naoki; Ogawa, Takeshi; Lai, Fangyuan; Kusumoto, Kenji

    2016-12-01

    Platelet-rich plasma (PRP) contains a high concentration of several growth factors and contributes to soft-tissue engineering and wound healing. However, the effect of PRP on human dermal fibroblast proliferation and responses is unknown. This was investigated in the present study using PRP prepared from the whole human blood using the double-spin method. Human dermal fibroblast cultures were established from skin samples collected during plastic surgery. Platelet concentration and growth factor levels in PRP were estimated, and a cell proliferation assay was carried out after PRP treatment. The role of Ras-dependent extracellular signal-regulated kinase (ERK)1/2 in the effects of PRP was investigated in human dermal fibroblasts by suppressing ERK1/2 expression with an inhibitor or by short interfering (si)RNA-mediated knockdown, and assessing ERK1/2 phosphorylation by western blotting as well as proliferation in PRP-treated cells. We found that PRP stimulated human dermal fibroblast proliferation, which was suppressed by ERK1/2 inhibitor treatment (P < 0.01). ERK1/2 phosphorylation was increased in the presence of PRP, while siRNA-mediated knockdown of ERK1/2 blocked cell proliferation normally induced by PRP treatment (P < 0.01). These results demonstrate that PRP induces human dermal fibroblast proliferation via activation of ERK1/2 signaling. Our findings provide a basis for the development of agents that can promote wound healing and can be applied to soft-tissue engineering.

  8. Stimulation of MMP-11 (stromelysin-3 expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Matthaei Klaus I

    2004-07-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14 and stromelysin-3 (MMP-11 are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. Methods To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs were: a treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b grown on collagens I, IV and V; c treated with fibronectin, con-A and matrigel; and d co-cultured with a range of HBC (human breast cancer cell lines of varied invasive and metastatic potential. Results Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. Conclusion We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms.

  9. Prostaglandin E2 Stimulates the Production of Vascular Endothelial Growth Factor through the E-Prostanoid–2 Receptor in Cultured Human Lung Fibroblasts

    Science.gov (United States)

    Nakanishi, Masanori; Sato, Tadashi; Nelson, Amy J.; Farid, Maha; Michalski, Joel; Kanaji, Nobuhiro; Wang, Xingqi; Basma, Hesham; Patil, Amol; Goraya, Jadvinder; Liu, Xiangde; Togo, Shinsaku; L. Toews, Myron; Holz, Olaf; Muller, Kai-Christian; Magnussen, Helgo

    2012-01-01

    Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E2 (PGE2) acts on a set of E-prostanoid (EP) receptors that activate multiple signal transduction pathways leading to downstream responses. We investigated the modulation by PGE2 of VEGF release by human lung fibroblasts. Human lung fibroblasts were cultured until reaching 90% confluence in tissue culture plates, after which the culture media were changed to serum-free Dulbecco's modified Eagle's medium, with or without PGE2, and with specific agonists or antagonists for each EP receptor. After 2 days, culture media were assayed for VEGF by ELISA. The results demonstrated that PGE2 and the EP2 agonist ONO-AE1-259-01 significantly stimulated the release of VEGF in a concentration-dependent manner. Agonists for other EP receptors did not stimulate the release of VEGF. The stimulatory effect of PGE2 was blocked by the EP2 antagonist AH6809, but was not blocked by antagonists for other EP receptors. The protein kinase–A (PKA) inhibitor KT-5720 also blocked the stimulatory effect of PGE2. The increased release of VEGF induced by PGE2 was accompanied by a transient increase in the concentration of VEGF mRNA. These findings demonstrate that PGE2 can modulate the release of VEGF by human lung fibroblasts through its actions in the EP2 receptor/PKA pathway. This activity may contribute to the maintenance of pulmonary microvasculature in the alveolar wall. PMID:22298530

  10. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  11. Acemannan stimulates gingival fibroblast proliferation; expressions of keratinocyte growth factor-1, vascular endothelial growth factor, and type I collagen; and wound healing.

    Science.gov (United States)

    Jettanacheawchankit, Suwimon; Sasithanasate, Siriruk; Sangvanich, Polkit; Banlunara, Wijit; Thunyakitpisal, Pasutha

    2009-04-01

    Aloe vera has long been used as a traditional medicine for inducing wound healing. Gingival fibroblasts (GFs) play an important role in oral wound healing. In this study, we investigated the effects of acemannan, a polysaccharide extracted from Aloe vera gel, on GF proliferation; keratinocyte growth factor-1 (KGF-1), vascular endothelial growth factor (VEGF), and type I collagen production; and oral wound healing in rats. [(3)H]-Thymidine incorporation assay and ELISA were used. Punch biopsy wounds were created at the hard palate of male Sprague Dawley rats. All treatments (normal saline; 0.1% triamcinolone acetonide; plain 1% Carbopol; and Carbopol containing 0.5%, 1%, and 2% acemannan (w/w)) were applied daily. Wounded areas and histological features were observed at day 7 after treatment. From our studies, acemannan at concentrations of 2, 4, 8, and 16 mg/ml significantly induced cell proliferation (P<0.05). Acemannan concentrations between 2 - 16 mg/ml significantly stimulated KGF-1, VEGF, and type I collagen expressions (P<0.05). Wound healing of animals receiving Carbopol containing 0.5% acemannan (w/w) was significantly better than that of the other groups (P<0.05). These findings suggest that acemannan plays a significant role in the oral wound healing process via the induction of fibroblast proliferation and stimulation of KGF-1, VEGF, and type I collagen expressions.

  12. A bioreactor for the dynamic mechanical stimulation of vocal-fold fibroblasts based on vibro-acoustography

    Science.gov (United States)

    Chan, Roger W.; Rodriguez, Maritza

    2005-09-01

    During voice production, the vocal folds undergo airflow-induced self-sustained oscillation at a fundamental frequency of around 100-1000 Hz, with an amplitude of around 1-3 mm. The vocal-fold extracellular matrix (ECM), with appropriate tissue viscoelastic properties, is optimally tuned for such vibration. Vocal-fold fibroblasts regulate the gene expressions for key ECM proteins (e.g., collagen, fibronectin, fibromodulin, and hyaluronic acid), and these expressions are affected by the stress fields experi- enced by the fibroblasts. This study attempts to develop a bioreactor for cultivating cells under a micromechanical environment similar to that in vivo, based on the principle of vibro-acoustography. Vocal-fold fibroblasts from primary culture were grown in 3D, biodegradable scaffolds, and were excited dynamically by the radiation force generated by amplitude modulation of two confocal ultrasound beams of slightly different frequencies. Low-frequency acoustic radiation force was applied to the scaffold surface, and its vibratory response was imaged by videostroboscopy. A phantom tissue (standard viscoelastic material) with known elastic modulus was also excited and its vibratory frequency and amplitude were measured by videostroboscopy. Results showed that the bioreactor was capable of delivering mechanical stimuli to the tissue constructs in a physiological frequency range (100-1000 Hz), supporting its potential for vocal-fold tissue engineering applications. [Work supported by NIH Grant R01 DC006101.

  13. Compound K inhibits MMP-1 expression through suppression of c-Src-dependent ERK activation in TNF-α-stimulated dermal fibroblast.

    Science.gov (United States)

    Lee, Chang Seok; Bae, Il-Hong; Han, Jiwon; Choi, Gye-young; Hwang, Kyung-Hwan; Kim, Dong-Hyun; Yeom, Myeong-Hun; Park, Young-Ho; Park, Miyoung

    2014-11-01

    Compound K (CK) is one of the major metabolites of ginsenosides exhibiting a variety of pharmacological properties such as anti-ageing, anti-oxidation and anti-inflammatory activities. However, the protective efficacy of CK in abnormal skin conditions with inflammatory responses was not examined. Here, we investigated the effects of CK on matrix metalloproteinase-1 (MMP-1) and type I procollagen production in tumor necrosis factor-α (TNF-α)-stimulated human skin fibroblasts HS68 cells and human skin equivalents. We found that CK suppressed MMP-1 secretion and increased the level of reduced type I procollagen secretion, caused by the inhibition of extracellular signal-regulated kinase (ERK) activation, but not p38 and c-Jun N-terminal kinase (JNK) activation in TNF-α-stimulated HS68 cells. Then, we focused on the involvement of the c-Src and epidermal growth factor receptor (EGFR) as upstream signalling molecules for ERK activation by TNF-α in HS68 cells. CK suppressed the phosphorylation of c-Src/EGFR by TNF-α, which led to the inactivation of downstream signalling molecules including AKT and MEK. In addition, CK suppressed AP-1 (c-jun and c-fos) phosphorylation as downstream transcription factors of active ERK for MMP-1 expression in TNFα-stimulated HS68 cells. These results showed novel mechanisms by which CK inhibits TNF-α-induced MMP-1 expression through the inactivation of c-Src/EGFR-dependent ERK/AP-1 signalling pathway, resulting in the inhibition of collagen degradation in human fibroblast cells. Therefore, CK may be a promising protective agent for the treatment of inflammatory skin conditions such as skin ageing and atopic dermatitis.

  14. In vitro cultured fetal fibroblasts have myofibroblast-associated characteristics and produce a fibrotic-like environment upon stimulation with TGF-β1: Is there a thin line between fetal scarless healing and fibrosis?

    Science.gov (United States)

    Walraven, M; Akershoek, J J; Beelen, R H J; Ulrich, M M W

    2017-03-01

    Transforming growth factor-β (TGF-β) is a cytokine occurring in three isoforms with an important function in development and wound healing. In wound healing, prolonged TGF-β signaling results in myofibroblast differentiation and fibrosis. In contrast, the developing second-trimester fetal skin contains high levels of all three TGF-β isoforms but still has the intrinsic capacity to heal without scarring. Insight into TGF-β signal transduction during fetal wound healing might lead to methods to control the signaling pathway during adult wound healing. In this study, we imitated wound healing in vitro by stimulating fibroblasts with TGF-β1 and examining myofibroblast differentiation. The aim was to gain insight into TGF-β signaling in human fibroblasts from fetal and adult dermis. First, TGF-β1 stimulation resulted in similar or even more severe upregulation of myofibroblast-associated genes in fetal fibroblasts compared to adult fibroblasts. Second, fetal fibroblasts also had higher protein levels of myofibroblast-marker α-smooth muscle actin (α-SMA). Third, stimulated fetal fibroblasts in collagen matrices had higher protein levels of α-SMA, produced more of the fibrotic protein fibronectin splice-variant extra domain A (FnEDA), and showed enhanced contraction. Finally, fetal fibroblasts also produced significant higher levels of TGF-β1. Altogether, these data show that in vitro cultured fetal fibroblasts have myofibroblast-associated characteristics and do produce a fibrotic environment. As healthy fetal skin has high levels of TGF-β1, FnEDA, and collagen-III as well, these findings correlate with the in vivo situation. Therefore, our study demonstrates that there are similarities between fetal skin development and fibrosis and shows the necessity to discriminate between these processes.

  15. Similar in vitro effects and pulp regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte-colony stimulating factor.

    Science.gov (United States)

    Takeuchi, N; Hayashi, Y; Murakami, M; Alvarez, F J; Horibe, H; Iohara, K; Nakata, K; Nakamura, H; Nakashima, M

    2015-01-01

    Granulocyte-colony stimulating factor (G-CSF) has been shown to have combinatorial trophic effects with dental pulp stem cells for pulp regeneration. The aim of this investigation is to examine the effects of basic fibroblast growth factor (bFGF) in vitro and in vivo compared with those of G-CSF and to assess the potential utility of bFGF as an alternative to G-CSF for pulp regeneration. Five different types of cells were examined in the in vitro effects of bFGF on cell migration, proliferation, anti-apoptosis, neurite outgrowth, angiogenesis, and odontogenesis compared with those of G-CSF. The in vivo regenerative potential of pulp tissue including vasculogenesis and odontoblastic differentiation was also compared using an ectopic tooth transplantation model. Basic fibroblast growth factor was similar to G-CSF in high migration, proliferation and anti-apoptotic effects and angiogenic and neurite outgrowth stimulatory activities in vitro. There was no significant difference between bFGF and G-CSF in the regenerative potential in vivo. The potential utility of bFGF for pulp regeneration is demonstrated as a homing/migration factor similar to the influence of G-CSF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Inhibitory effects of LPA1 on cell motile activities stimulated by hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone in fibroblast 3T3 cells.

    Science.gov (United States)

    Hirane, Miku; Araki, Mutsumi; Dong, Yan; Honoki, Kanya; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

    2013-11-08

    Reactive oxygen species (ROS) are known to mediate a variety of biological responses, including cell motility. Recently, we indicated that lysophosphatidic acid (LPA) receptor-3 (LPA3) increased cell motile activity stimulated by hydrogen peroxide. In the present study, we assessed the role of LPA1 in the cell motile activity mediated by ROS in mouse fibroblast 3T3 cells. 3T3 cells were treated with hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) at concentrations of 0.1 and 1 μM for 48 h. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3 cells treated with hydrogen peroxide and DMNQ were significantly higher than those of untreated cells. 3T3 cells treated with hydrogen peroxide and DMNQ showed elevated expression levels of the Lpar3 gene, but not the Lpar1 and Lpar2 genes. To investigate the effects of LPA1 on the cell motile activity induced by hydrogen peroxide and DMNQ, Lpar1-overexpressing (3T3-a1) cells were generated from 3T3 cells and treated with hydrogen peroxide and DMNQ. The cell motile activities stimulated by hydrogen peroxide and DMNQ were markedly suppressed in 3T3-a1 cells. These results suggest that LPA signaling via LPA1 inhibits the cell motile activities stimulated by hydrogen peroxide and DMNQ in 3T3 cells.

  17. PAMPs and DAMPs stimulate the expression of pro-inflammatory cytokines in vitro in a fibroblast cell-line from rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Ossum, C.G.; Nielsen, Michael Engelbrecht

    activates downstream signalling pathways, which subsequently leads to expression of pro-inflammatory cytokines and chemokines. DAMPs released from necrotic cells may also bind to and activate similar downstream signalling events. In telosts was found that mechanical damage of the muscle tissue using sterile...... needles induced a very rapid expression of the pro-inflammatory cytokines IL-1β, IL-8 and IL-10 as measured by real-time PCR. The results imply that cells located in the muscular tissue in addition to recruited cells are involved in the observed increased cytokine / chemokine expression. It is believed...... in this evolutionary lineage of the bony fishes. The expression of TLR-3 and -9 receptors were significantly up-regulated following physical damage of muscle tissue as well as in stimulated fibroblasts, where LPS induced both TLR-3 and -9, supernatant from sonicated cells only TLR-9 while debris caused no induction...

  18. Expression levels of novel cytokine IL-32 in periodontitis and its role in the suppression of IL-8 production by human gingival fibroblasts stimulated with Porphyromonas gingivalis

    Directory of Open Access Journals (Sweden)

    Kazuhisa Ouhara

    2012-03-01

    Full Text Available Background:IL-32 was recently found to be elevated in the tissue of rheumatoid arthritis and inflammatory bowel disease. Periodontitis is a chronic inflammatory disease caused by polymicrobial infections that result in soft tissue destruction and alveolar bone loss. Although IL-32 is also thought to be associated with periodontal disease, its expression and possible role in periodontal tissue remain unclear. Therefore, this study investigated the expression patterns of IL-32 in healthy and periodontally diseased gingival tissue. The expression of IL-32 in cultured human gingival fibroblasts (HGF as well as effects of autocrine IL-32 on IL-8 production from HGF were also examined.Methods:Periodontal tissue was collected from both healthy volunteers and periodontitis patients, and immunofluorescent staining was performed in order to determine the production of IL-32. Using real-time PCR and ELISA, mRNA expression and protein production of IL-32 in HGF, stimulated by Porphyromonas gingivalis (Pg, were also investigated.Results:Contrary to our expectation, the production of IL-32 in the periodontitis patients was significantly lower than in the healthy volunteers. According to immunofluorescent microscopy, positive staining for IL-32 was detected in prickle and basal cell layers in the epithelium as well as fibroblastic cells in connective tissue. Addition of fixed Pg in vitro was found to suppress the otherwise constitutive expression of IL-32 mRNA and protein in HGF. However, recombinant IL-32 in vitro inhibited the expression of IL-8 mRNA by HGF stimulated with Pg. Interestingly, anti-IL-32 neutralizing antibody upregulated the IL-8 mRNA expression in non-stimulated HGF, indicating that constitutive expression of IL-32 in HGF suppressed IL-8 mRNA expression in the absence of bacterial stimulation.Conclusion:These results indicate that IL-32 is constitutively produced by HGF which can be suppressed by Pg and may play a role in the downregulation

  19. Stimulation of the Fibrillar Collagen and Heat Shock Proteins by Nicotinamide or Its Derivatives in Non-Irradiated or UVA Radiated Fibroblasts, and Direct Anti-Oxidant Activity of Nicotinamide Derivatives

    Directory of Open Access Journals (Sweden)

    Neena Philips

    2015-05-01

    Full Text Available In skin aging, from intrinsic factors or exposure to ultraviolet (UV radiation, there is loss of structural fibrillar collagen and regulatory heat shock proteins. Phenolic compounds, with hydroxyl groups attached to an aromatic ring, have antioxidative and anti-inflammatory properties. Nicotinamide is an amide derivative of niacin or vitamin B3, with an amide linked to an aromatic ring, with UV absorptive, antioxidant, anti-inflammatory and anti-cell death/apoptosis properties. The goal of this research was to investigate the anti-skin aging mechanism of nicotinamide and its derivatives, 2,6-dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide (collectively niacin derivatives, through the stimulation of fibrillar collagens (type I, III and V, at protein and/or promoter levels and the expression of heat shock proteins (HSP-27, 47, 70, and 90 in non-irradiated or UVA radiated dermal fibroblasts; and from its direct antioxidant activity. UVA radiation inhibited the expression of types I and III collagen, and HSP-47 in dermal fibroblasts. The niacin derivatives significantly and similarly stimulated the expression of types I (transcriptionally, III and V collagens in non-irradiated, and UVA radiated fibroblasts indicating predominant effects. The 2,6-dihydroxynicotinamide had greater stimulatory effect on types I and III collagen in the non-irradiated, and UVA radiated fibroblasts, as well as greater direct antioxidant activity than the other niacin derivatives. The niacin derivatives, with a few exceptions, stimulated the expression of HSP-27, 47, 70 and 90 in non-irradiated, and UVA radiated fibroblasts. However, they had varied effects on the expression of the different HSPs in non-irradiated, and UVA radiated fibroblasts indicating non-predominant, albeit stimulatory, effect. Overall, nicotinamide and its derivatives have anti skin aging potential through the stimulation of fibrillar collagen and HSPs.

  20. Glucagon and Insulin Cooperatively Stimulate Fibroblast Growth Factor 21 Gene Transcription by Increasing the Expression of Activating Transcription Factor 4.

    Science.gov (United States)

    Alonge, Kimberly M; Meares, Gordon P; Hillgartner, F Bradley

    2017-03-31

    Previous studies have shown that glucagon cooperatively interacts with insulin to stimulate hepatic FGF21 gene expression. Here we investigated the mechanism by which glucagon and insulin increased FGF21 gene transcription in primary hepatocyte cultures. Transfection analyses demonstrated that glucagon plus insulin induction of FGF21 transcription was conferred by two activating transcription factor 4 (ATF4) binding sites in the FGF21 gene. Glucagon plus insulin stimulated a 5-fold increase in ATF4 protein abundance, and knockdown of ATF4 expression suppressed the ability of glucagon plus insulin to increase FGF21 expression. In hepatocytes incubated in the presence of insulin, treatment with a PKA-selective agonist mimicked the ability of glucagon to stimulate ATF4 and FGF21 expression. Inhibition of PKA, PI3K, Akt, and mammalian target of rapamycin complex 1 (mTORC1) suppressed the ability of glucagon plus insulin to stimulate ATF4 and FGF21 expression. Additional analyses demonstrated that chenodeoxycholic acid (CDCA) induced a 6-fold increase in ATF4 expression and that knockdown of ATF4 expression suppressed the ability of CDCA to increase FGF21 gene expression. CDCA increased the phosphorylation of eIF2α, and inhibition of eIF2α signaling activity suppressed CDCA regulation of ATF4 and FGF21 expression. These results demonstrate that glucagon plus insulin increases FGF21 transcription by stimulating ATF4 expression and that activation of cAMP/PKA and PI3K/Akt/mTORC1 mediates the effect of glucagon plus insulin on ATF4 expression. These results also demonstrate that CDCA regulation of FGF21 transcription is mediated at least partially by an eIF2α-dependent increase in ATF4 expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. The Water Fraction of Calendula officinalis Hydroethanol Extract Stimulates In Vitro and In Vivo Proliferation of Dermal Fibroblasts in Wound Healing.

    Science.gov (United States)

    Dinda, Manikarna; Mazumdar, Swagata; Das, Saurabh; Ganguly, Durba; Dasgupta, Uma B; Dutta, Ananya; Jana, Kuladip; Karmakar, Parimal

    2016-10-01

    The active fraction and/or compounds of Calendula officinalis responsible for wound healing are not known yet. In this work we studied the molecular target of C. officinalis hydroethanol extract (CEE) and its active fraction (water fraction of hydroethanol extract, WCEE) on primary human dermal fibroblasts (HDF). In vivo, CEE or WCEE were topically applied on excisional wounds of BALB/c mice and the rate of wound contraction and immunohistological studies were carried out. We found that CEE and only its WCEE significantly stimulated the proliferation as well as the migration of HDF cells. Also they up-regulate the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in vitro. In vivo, CEE or WCEE treated mice groups showed faster wound healing and increased expression of CTGF and α-SMA compared to placebo control group. The increased expression of both the proteins during granulation phase of wound repair demonstrated the potential role of C. officinalis in wound healing. In addition, HPLC-ESI MS analysis of the active water fraction revealed the presence of two major compounds, rutin and quercetin-3-O-glucoside. Thus, our results showed that C. officinalis potentiated wound healing by stimulating the expression of CTGF and α-SMA and further we identified active compounds. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Reduced mitochondrial Ca(2+) transients stimulate autophagy in human fibroblasts carrying the 13514A>G mutation of the ND5 subunit of NADH dehydrogenase.

    Science.gov (United States)

    Granatiero, V; Giorgio, V; Calì, T; Patron, M; Brini, M; Bernardi, P; Tiranti, V; Zeviani, M; Pallafacchina, G; De Stefani, D; Rizzuto, R

    2016-02-01

    Mitochondrial disorders are a group of pathologies characterized by impairment of mitochondrial function mainly due to defects of the respiratory chain and consequent organellar energetics. This affects organs and tissues that require an efficient energy supply, such as brain and skeletal muscle. They are caused by mutations in both nuclear- and mitochondrial DNA (mtDNA)-encoded genes and their clinical manifestations show a great heterogeneity in terms of age of onset and severity, suggesting that patient-specific features are key determinants of the pathogenic process. In order to correlate the genetic defect to the clinical phenotype, we used a cell culture model consisting of fibroblasts derived from patients with different mutations in the mtDNA-encoded ND5 complex I subunit and with different severities of the illness. Interestingly, we found that cells from patients with the 13514A>G mutation, who manifested a relatively late onset and slower progression of the disease, display an increased autophagic flux when compared with fibroblasts from other patients or healthy donors. We characterized their mitochondrial phenotype by investigating organelle turnover, morphology, membrane potential and Ca(2+) homeostasis, demonstrating that mitochondrial quality control through mitophagy is upregulated in 13514A>G cells. This is due to a specific downregulation of mitochondrial Ca(2+) uptake that causes the stimulation of the autophagic machinery through the AMPK signaling axis. Genetic and pharmacological manipulation of mitochondrial Ca(2+) homeostasis can revert this phenotype, but concurrently decreases cell viability. This indicates that the higher mitochondrial turnover in complex I deficient cells with this specific mutation is a pro-survival compensatory mechanism that could contribute to the mild clinical phenotype of this patient.

  3. The role of macrophage migration inhibitory factor in mast cell-stimulated fibroblast proliferation and collagen production.

    Science.gov (United States)

    Ningyan, Gu; Xu, Yao; Hongfei, Shi; Jingjing, Chen; Min, Chen

    2015-01-01

    Current clinical and translational studies have shown that mast cell plays a pivotal role in multiple fibrotic diseases including scleroderma. However, the lack of mature human mast cell culture model exhibits a major obstacle for further dissection of cytokines and signaling molecules required for mast cell mediated fibrosis in various diseases. Macrophage Migration Inhibitory Factor is a mast cell released pro-inflammatory cytokine which is deregulated in scleroderma patients and is also involved in non-scleroderma related fibrosis. In the current study, we successfully generated a practical and reliable human mast cell culture system with bone marrow CD34+ hematopietic precursors. The derivative mast cell is normal in terms of both morphology and function as manifested by normal degranulation. More importantly, we were able to show mast cell conditioned medium as well as MIF supplementation augments fibroblast proliferation and collagen synthesis. This positive regulatory effect of mast cell conditioned medium can be dampened by MIF antibody. In addition, MIF-knockdown significantly inhibits pro-fibrotic activities of CD34+ hematopietic precursor derived mast cells. These data strongly suggest that mast cell released MIF is required for mast cell mediated fibrogenic activities. The current manuscript seems to be the first mechanistic report showing the significance of MIF in mast cell mediated fibrosis, which may pave the way for the development of potential MIF-targeted therapy for fibrotic diseases to a further extent. Moreover, we strongly believe mast cell culture and differentiation model as well as corresponding genetic manipulation methodology will be helpful in characterizing novel mast cell based therapeutic targets.

  4. Activating the expression of human K-rasG12D stimulates oncogenic transformation in transgenic goat fetal fibroblast cells.

    Science.gov (United States)

    Gong, Jianhua; Wang, Zhongde; Polejaeva, Irina; Salgia, Ravi; Kao, Chien-Min; Chen, Chin-Tu; Chen, Guangchun; Chen, Liaohai

    2014-01-01

    Humane use of preclinical large animal cancer models plays a critical role in understanding cancer biology and developing therapeutic treatments. Among the large animal candidates, goats have great potentials as sustainable sources for large animal cancer model development. Goats are easier to handle and cheaper to raise. The genome of the goats has been sequenced recently. It has been known that goats develop skin, adrenal cortex, breast and other types of cancers. Technically, goats are subject to somatic cell nuclear transfer more efficiently and exhibit better viability through the cloning process. Towards the development of a goat cancer model, we created a transgenic goat fetal fibroblast (GFF) cell as the donor cell for SCNT. Human mutated K-ras (hK-rasG12D) was chosen as the transgene, as it is present in 20% of cancers. Both hK-rasG12D and a herpes simplex viral thymidine kinase (HSV1-tk) reporter genes, flanked by a pair of LoxP sites, were knocked in the GFF endogenous K-ras locus through homologous recombination. Following Cre-mediated activation (with a 95% activation efficiency), hK-rasG12D and HSV1-tk were expressed in the transgenic GFF cells, evidently through the presence of corresponding mRNAs, and confirmed by HSV1-tk protein function assay. The hK-rasG12D expressing GFF cells exhibited enhanced proliferation rates and an anchorage-independent growth behavior. They were able to initiate tumor growth in athymic nude mice. In conclusion, after activating hK-rasG12D gene expression, hK-rasG12D transgenic GFF cells were transformed into tumorgenesis cells. Transgenic goats via SCNT using the above-motioned cells as the donor cells have been established.

  5. Activating the expression of human K-rasG12D stimulates oncogenic transformation in transgenic goat fetal fibroblast cells.

    Directory of Open Access Journals (Sweden)

    Jianhua Gong

    Full Text Available Humane use of preclinical large animal cancer models plays a critical role in understanding cancer biology and developing therapeutic treatments. Among the large animal candidates, goats have great potentials as sustainable sources for large animal cancer model development. Goats are easier to handle and cheaper to raise. The genome of the goats has been sequenced recently. It has been known that goats develop skin, adrenal cortex, breast and other types of cancers. Technically, goats are subject to somatic cell nuclear transfer more efficiently and exhibit better viability through the cloning process. Towards the development of a goat cancer model, we created a transgenic goat fetal fibroblast (GFF cell as the donor cell for SCNT. Human mutated K-ras (hK-rasG12D was chosen as the transgene, as it is present in 20% of cancers. Both hK-rasG12D and a herpes simplex viral thymidine kinase (HSV1-tk reporter genes, flanked by a pair of LoxP sites, were knocked in the GFF endogenous K-ras locus through homologous recombination. Following Cre-mediated activation (with a 95% activation efficiency, hK-rasG12D and HSV1-tk were expressed in the transgenic GFF cells, evidently through the presence of corresponding mRNAs, and confirmed by HSV1-tk protein function assay. The hK-rasG12D expressing GFF cells exhibited enhanced proliferation rates and an anchorage-independent growth behavior. They were able to initiate tumor growth in athymic nude mice. In conclusion, after activating hK-rasG12D gene expression, hK-rasG12D transgenic GFF cells were transformed into tumorgenesis cells. Transgenic goats via SCNT using the above-motioned cells as the donor cells have been established.

  6. Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

    Energy Technology Data Exchange (ETDEWEB)

    An, Caiyan [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia (China); Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Wu, Taoya; Bao, Muqiri; Bao, Liang [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Tobo, Masayuki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Damirin, Alatangaole, E-mail: bigaole@imu.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China)

    2015-05-01

    The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

  7. Uterine Fibroid Embolization (UFE)

    Science.gov (United States)

    ... embolization. This occurs when fibroids located inside the uterine cavity detach after embolization. Women with this problem may require a procedure called D & C (dilatation and curettage) to ... who undergo uterine fibroid embolization, normal menstrual cycles resume after the ...

  8. Influence of a pre-stimulation with chronic low-dose UVB on stress response mechanisms in human skin fibroblasts.

    Science.gov (United States)

    Drigeard Desgarnier, Marie-Catherine; Fournier, Frédéric; Droit, Arnaud; Rochette, Patrick J

    2017-01-01

    Exposure to solar ultraviolet type B (UVB), through the induction of cyclobutane pyrimidine dimer (CPD), is the major risk factor for cutaneous cancer. Cells respond to UV-induced CPD by triggering the DNA damage response (DDR) responsible for signaling DNA repair, programmed cell death and cell cycle arrest. Underlying mechanisms implicated in the DDR have been extensively studied using single acute UVB irradiation. However, little is known concerning the consequences of chronic low-dose of UVB (CLUV) on the DDR. Thus, we have investigated the effect of a CLUV pre-stimulation on the different stress response pathways. We found that CLUV pre-stimulation enhances CPD repair capacity and leads to a cell cycle delay but leave residual unrepaired CPD. We further analyzed the consequence of the CLUV regimen on general gene and protein expression. We found that CLUV treatment influences biological processes related to the response to stress at the transcriptomic and proteomic levels. This overview study represents the first demonstration that human cells respond to chronic UV irradiation by modulating their genotoxic stress response mechanisms.

  9. Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen.

    Science.gov (United States)

    Simón, C; Garcia Velasco, J J; Valbuena, D; Peinado, J A; Moreno, C; Remohí, J; Pellicer, A

    1998-08-01

    To analyze the effect on uterine receptivity of a decrease in E2 levels during the preimplantation period with the use of a step-down regimen in high responders undergoing IVF. Prospective controlled clinical study. The Instituto Valenciano de Infertilidad. High responders in whom at least one previous IVF attempt failed in which 3-4 good-quality embryos were transferred and E2 levels were >3,000 pg/mL on the day of hCG administration. Gonadotropins were administered according to two different protocols. Blood samples were collected and IVF was performed. Serum E2 levels and reproductive outcome of IVF. Estradiol levels on the day of hCG administration and throughout the preimplantation period and the number of oocytes collected were significantly lower with the use of the step-down regimen than during the previous failed cycle in which the standard protocol was used. The fertilization rate was similar and the number of good-quality embryos transferred was comparable. However, the implantation and pregnancy rates were significantly improved in patients who underwent the step-down regimen compared with those who received the standard protocol. With the use of a step-down regimen with FSH in high responders, our clinical results demonstrate that uterine receptivity can be improved when E2 levels are decreased during the preimplantation period.

  10. Pinoresinol-4,4'-di-O-beta-D-glucoside from Valeriana officinalis root stimulates calcium mobilization and chemotactic migration of mouse embryo fibroblasts.

    Science.gov (United States)

    Do, Kee Hun; Choi, Young Whan; Kim, Eun Kyoung; Yun, Sung Ji; Kim, Min Sung; Lee, Sun Young; Ha, Jung Min; Kim, Jae Ho; Kim, Chi Dae; Son, Beung Gu; Kang, Jum Soon; Khan, Ikhlas A; Bae, Sun Sik

    2009-06-01

    Lignans are major constituents of plant extracts and have important pharmacological effects on mammalian cells. Here we showed that pinoresinol-4,4'-di-O-beta-D-glucoside (PDG) from Valeriana officinalis induced calcium mobilization and cell migration through the activation of lysophosphatidic acid (LPA) receptor subtypes. Stimulation of mouse embryo fibroblast (MEF) cells with 10 microM PDG resulted in strong stimulation of MEF cell migration and the EC(50) was about 2 microM. Pretreatment with pertussis toxin (PTX), an inhibitor of G(i) protein, completely blocked PDG-induced cell migration demonstrating that PDG evokes MEF cell migration through the activation of the G(i)-coupled receptor. Furthermore, pretreatment of MEF cells with Ki16425 (10 microM), which is a selective antagonist for LPA(1) and LPA(3) receptors, completely blocked PDG-induced cell migration. Likewise, PDG strongly induced calcium mobilization, which was also blocked by Ki16425 in a dose-dependent manner. Prior occupation of the LPA receptor with LPA itself completely blocked PDG-induced calcium mobilization. Finally, PDG-induced MEF cell migration was attenuated by pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor such as LY294002. Cells lacking downstream mediator of PI3K such as Akt1 and Akt2 (DKO cells) showed loss of PDG-induced migration. Re-expression of Akt1 (but not Akt2) completely restored PDG-induced DKO cell migration. Given these results, we conclude that PDG is a strong inducer of cell migration. We suggest that the pharmacological action of PDG may occur through the activation of an LPA receptor whereby activation of PI3K/Akt signaling pathway mediates PDG-induced MEF cell migration.

  11. Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.

    Directory of Open Access Journals (Sweden)

    Jyh-Horng Wang

    Full Text Available Fibroblast-like synoviocytes (FLS play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs. The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol, the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E(2, and matrix metalloproteinases (MMPs by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL-induced cytokine expression in a concentration-dependent manner (2.5-25 µg/mL. In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases.

  12. Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex

    Directory of Open Access Journals (Sweden)

    Ganesh Kolumam

    2015-07-01

    Full Text Available Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin.

  13. Structural alteration of cell surface heparan sulfate through the stimulation of the signaling pathway for heparan sulfate 6-O-sulfotransferase-1 in mouse fibroblast cells.

    Science.gov (United States)

    Nishida, Mitsutaka; Kozakai, Takeru; Nagami, Keitaro; Kanamaru, Yoshihiro; Yabe, Tomio

    2014-01-01

    Heparan sulfate (HS) is a randomly sulfated polysaccharide that is present on the cell surface and in the extracellular matrix. The sulfated structures of HS were synthesized by multiple HS sulfotransferases, thereby regulating various activities such as growth factor signaling, cell differentiation, and tumor metastasis. Therefore, if the sulfated structures of HS could be artificially controlled, those manipulations would help to understand the various functions depending on HS. However, little knowledge is currently available to realize the mechanisms controlling the expression of such enzymes. In this study, we found that the ratio of 6-O-sulfated disaccharides increased at 3 h after adrenaline stimulation in mouse fibroblast cells. Furthermore, adrenaline-induced up-regulation of HS 6-O-sulfotransferase-1 (6-OST-1) was controlled by Src-ERK1/2 signaling pathway. Finally, inhibiting the signaling pathways for 6-OST-1 intentionally suppressed the adrenaline-induced structural alteration of HS. These observations provide fundamental insights into the understanding of structural alterations in HS by extracellular cues.

  14. Effect of sequential medium with fibroblast growth factor-10 and follicle stimulating hormone on in vitro development of goat preantral follicles.

    Science.gov (United States)

    Almeida, A P; Magalhães-Padilha, D M; Araújo, V R; Costa, S L; Chaves, R N; Lopes, C A P; Donato, M A M; Peixoto, C A; Campello, C C; Junior, J Buratini; Figueiredo, J R

    2015-01-01

    A sequential medium with fibroblast growth factor-10 (FGF-10) and follicle stimulating hormone (FSH) was evaluated on the survival, ultrastructure, activation and growth rate of caprine preantral follicles submitted to long-term culture, aiming to establish an ideal in vitro culture system. Ovarian fragments were cultured for 16 days in α-MEM(+) alone or supplemented with FGF-10 and/or FSH added sequentially on different days of culture. Ovarian fragments were cultured during the first (days 0-8) and second (days 8-16) halves of the culture period, generating 10 treatments: α-MEM(+)/α-MEM(+) (cultured control), FSH/FSH, FSH/FGF-10, FSH/FSH+FGF-10, FGF-10/FGF-10, FGF-10/FSH, FGF-10/FSH+FGF-10, FSH+FGF-10/FSH+FGF-10, FSH+FGF-10/FSH and FSH+FGF-10/FGF-10. Follicle morphology, viability and ultrastructure were analyzed. The FSH/FGF-10 treatment showed a higher (Pgrowth in goat preantral follicles cultured in vitro.

  15. Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex.

    Science.gov (United States)

    Kolumam, Ganesh; Chen, Mark Z; Tong, Raymond; Zavala-Solorio, Jose; Kates, Lance; van Bruggen, Nicholas; Ross, Jed; Wyatt, Shelby K; Gandham, Vineela D; Carano, Richard A D; Dunshee, Diana Ronai; Wu, Ai-Luen; Haley, Benjamin; Anderson, Keith; Warming, Søren; Rairdan, Xin Y; Lewin-Koh, Nicholas; Zhang, Yingnan; Gutierrez, Johnny; Baruch, Amos; Gelzleichter, Thomas R; Stevens, Dale; Rajan, Sharmila; Bainbridge, Travis W; Vernes, Jean-Michel; Meng, Y Gloria; Ziai, James; Soriano, Robert H; Brauer, Matthew J; Chen, Yongmei; Stawicki, Scott; Kim, Hok Seon; Comps-Agrar, Laëtitia; Luis, Elizabeth; Spiess, Christoph; Wu, Yan; Ernst, James A; McGuinness, Owen P; Peterson, Andrew S; Sonoda, Junichiro

    2015-07-01

    Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin.

  16. Alterations in uterine hemodynamics caused by uterine fibroids and their impact on in vitro fertilization outcomes

    OpenAIRE

    Moon, Jei-Won; Kim, Chung-Hoon; Kim, Jun-Bum; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2015-01-01

    Objective To investigate the impact of fibroids on the blood flow of the uterine and subendometrial arteries and in vitro fertilization (IVF) outcomes. Methods In this study, we analyzed 86 IVF/intracytoplasmic sperm injection (ICSI) cycles in which a gonadotropin-releasing hormone antagonist protocol was used for controlled ovarian stimulation between January 2008 and March 2009. The subjects comprised 86 infertile women with (fibroid group, n=43) or without (control group, n=43) uterine fib...

  17. A mutein of human basic fibroblast growth factor TGP-580 accelerates colonic ulcer healing by stimulating angiogenesis in the ulcer bed in rats.

    Science.gov (United States)

    Satoh, H; Szabo, S

    2015-10-01

    Previously, we reported that TGP-580, a mutein of human basic fibroblast growth factor (bFGF), accelerated the healing of gastric and duodenal ulcers in rats. In the present study, we examined the effect of TGP-580 on the healing of colonic ulcers. In male Sprague Dawley rats, ulcers were induced in the colon 6 cm from the anus by enema of 50 μl of 3% N-ethylmaleimide, a sulfhydryl alkylator. The lesions were examined under a dissecting microscope (x10). The concentration of bFGF in the ulcerated colon was measured by enzyme immunoassay, and both the distribution of bFGF and the density of microvessels in the ulcer bed were examined by immunohistochemical staining. The content of bFGF in the ulcerated colon was markedly increased associated with ulcer healing, and ulcer healing was significantly delayed by intravenous administration of a monoclonal antibody for bFGF (MAb 3H3) once daily for 10 days. In the ulcer bed, many cells such as fibroblasts, vascular endothelial cells and macrophages were positively stained with bFGF antiserum. TGP-580, human bFGF or dexamethasone was given intracolonally twice daily for 10 days, starting the day after ulcer induction. TGP-580 (0.2 - 20 μg/ml, 200 μl/rat) dose-dependently accelerated ulcer healing, and its effect was more than 10 times stronger than that of human bFGF. Density (μm/0.01 mm(2)) of microvessels in the ulcer bed was significantly increased by treatment with TGP-580, and there was a good correlation between the density of microvessels and the decrease of ulcerated area (R(2) = 0.633). On the other hand dexamethasone (20 μg/ml) inhibited angiogenesis in the ulcer bed and delayed ulcer healing. These results suggest that angiogenesis in the ulcer bed plays an important role in ulcer healing, and that bFGF mutein TGP-580 accelerated colonic ulcer healing, at least in part, by stimulating angiogenesis, whereas glucocorticoids may delay the healing by inhibiting angiogenesis.

  18. [Human uterine contractility during normal puerperium (author's transl)].

    Science.gov (United States)

    Romero-Salinas, G; Vera-Cázares, R; La Torre-Rasguido, F; Escalera-Villarreal, G; Bandera-González, B

    1980-01-01

    In order to determine the morphology and the normal values of uterine contractility during the puerperium, 26 patients with the following characteristics were studied: multiparous during puerperium, without recent episiotomy, with healthy cervix, absence of genital septic focus, uterine tumours or malformations; all of them breast feeding. In the hypothesis it was considered that the endogenous oxytocin increases and stimulates the mammary myoepithelium and uterine contractility. For recording uterine contractility, the technique of Jaumandreu and Hendricks was used. The recordings were made during the 24 hours postpartum, at 5, 10, 20, 30 and 40 days with a duration of 2 to 3 hours. All the studies were longitudinal. The change of human uterine contractility during normal puerperium were estimated. The range of the tonus was 22--41 mmHg, the intensity 5--18 mmHg, the frequency 17--23 contractions in 10 minutes, and the uterine activity 102--223 Montevideo Units.

  19. Alterations in uterine hemodynamics caused by uterine fibroids and their impact on in vitro fertilization outcomes.

    Science.gov (United States)

    Moon, Jei-Won; Kim, Chung-Hoon; Kim, Jun-Bum; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2015-12-01

    To investigate the impact of fibroids on the blood flow of the uterine and subendometrial arteries and in vitro fertilization (IVF) outcomes. In this study, we analyzed 86 IVF/intracytoplasmic sperm injection (ICSI) cycles in which a gonadotropin-releasing hormone antagonist protocol was used for controlled ovarian stimulation between January 2008 and March 2009. The subjects comprised 86 infertile women with (fibroid group, n=43) or without (control group, n=43) uterine fibroids. Patient characteristics were similar between the fibroid and control groups. The IVF/ICSI outcomes in patients with fibroids were similar to those of patients in the control group. The resistance index (RI) and pulsatile index (PI) of the uterine and subendometrial arteries on the day of embryo transfer were also comparable between the two groups. IVF outcomes and uterine hemodynamics in patients with multiple (≥2) fibroids were similar to those of patients with a single fibroid. However, clinical pregnancy and implantation rates were significantly lower in patients with fibroids who experienced uterine cavity distortion than in patients with fibroids who had a normal uterine cavity (both p<0.05). The RI and PI of the subendometrial artery were significantly higher on the day of embryo transfer in patients with fibroids who experienced uterine cavity distortion than in patients with fibroids who had a normal uterine cavity (both p<0.05). Fibroids which distorting the uterine cavity might impair the subendometrial artery blood flow clinical pregnancy rate and embryo implantation rate in infertile patients undergoing IVF. Otherwise, IVF outcomes were not influenced by the presence of uterine fibroids.

  20. Cellular mechanisms by which oxytocin stimulates uterine PGF2 alpha synthesis in bovine endometrium: roles of phospholipases C and A2.

    Science.gov (United States)

    Burns, P D; Graf, G A; Hayes, S H; Silvia, W J

    1997-05-01

    The objective of these experiments was to identify the cellular mechanisms by which oxytocin stimulates prostaglandin (PG) F2 alpha synthesis in bovine endometrial tissue. Uteri were collected on the day after spontaneous luteal regression. Caruncular endometrial explants were dissected and incubated in vitro to assess PGF2 alpha release or phospholipase (PL) C activity. Oxytocin (10(-6) M) stimulated PGF2 alpha release and PLC activity within 30 min of incubation (P 0.10). By comparing the time course of stimulation and dose-response relationships between PGF2 alpha and PLC activity, it appears that oxytocin may stimulate PGF2 alpha secretion by activating PLC. The effects of melittin and aristolochic acid indicate that PLA2 may play a role in mediating the stimulatory effect of oxytocin on PGF2 alpha secretion, as well.

  1. Uterine artery embolization to treat uterine fibroids

    Energy Technology Data Exchange (ETDEWEB)

    Machan, L.; Martin, M. [Univ. of British Columbia Hospital, Dept. of Radiology, Vancouver, BC (Canada)

    2001-06-01

    The first reported application of uterine artery embolization, in 1979, was to treat life-threatening hemorrhage after a failed hysterectomy. Since then, uterine artery embolization has been used very successfully to control acute or delayed post-partum hemorrhage, post-surgical hemorrhage and hemorrhage from ectopic pregnancy, to treat uterine arteriovenous malformations and as prophylaxis before high-risk surgery, such as cesarean delivery in women with placenta previa. In contrast to these proven but underutilized applications, uterine embolization for fibroids has, in a short time, achieved significant notice in the lay press and is being widely offered. Ravina and colleagues, first reported uterine fibroid shrinkage after embolization for the treatment of acute bleeding. Since then, his group has performed over 100 procedures with up to a 6-year follow-up. The cumulative clinical success rate for the treatment of abnormal uterine bleeding due to fibroids is reported to be approximately 85% and for treatment of pain or pressure symptoms, about 75%. Six-month follow-up sonography reveals an average reduction of fibroid size of approximately 40%. However, to date, no studies have compared patients who undergo embolization with a nontreatment cohort or with surgical intervention. (author)

  2. Stimulation of α7 nicotinic acetylcholine receptor regulates glutamate transporter GLAST via basic fibroblast growth factor production in cultured cortical microglia.

    Science.gov (United States)

    Morioka, Norimitsu; Harano, Sakura; Tokuhara, Masato; Idenoshita, Yuko; Zhang, Fang Fang; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2015-11-01

    The α7 nicotinic acetylcholine (nACh) receptor expressed in microglia has a crucial role in neuroprotection. Simulation of α7 nACh receptor leads to increased expression of glutamate/aspartate transporter (GLAST), which in turn decreases synaptic glutamate levels. However, the upregulation of GLAST in cultured rat cortical microglia appears long after (over 18 h) stimulation of the α7 nACh receptor with nicotine. Thus, the current study elucidated the pathway responsible for the induction of GLAST expression in cultured cortical microglia. Nicotine-induced GLAST mRNA expression was significantly inhibited by cycloheximide pretreatment, indicating that a protein intermediary, such as a growth factor, is required for GLAST expression. The expression of fibroblast growth factor-2 (FGF-2) mRNA in cortical microglia was significantly increased 6 and 12h after treatment with nicotine, and this increase was potently inhibited by pretreatment with methyllycaconitine, a selective α7 nACh receptor antagonist. The treatment with nicotine also significantly increased FGF-2 protein expression. Furthermore, treatment with recombinant FGF-2 increased GLAST mRNA, protein expression and (14)C-glutamate uptake, a functional measurement of GLAST activity. Conversely, pretreatment with PD173074, an inhibitor of FGF receptor (FGFR) tyrosine kinase, significantly prevented the nicotine-induced expression of GLAST mRNA, its protein and (14)C-glutamate uptake. Reverse transcription polymerase chain reaction confirmed FGFR1 mRNA expression was confined to cultured cortical microglia. Together, the current findings demonstrate that the neuroprotective effect of activation of microglial α7 nACh receptors could be due to the expression of FGF-2, which in turn increases GLAST expression, thereby clearing glutamate from synapse and decreasing glutamate neurotransmission.

  3. Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient mice.

    Science.gov (United States)

    Tsuji, Kiyomi; Maeda, Toyonobu; Kawane, Tetsuya; Matsunuma, Ayako; Horiuchi, Noboru

    2010-08-01

    Leptin is the LEP (ob) gene product secreted by adipocytes. We previously reported that leptin decreases renal expression of the 25-hydroxyvitamin D(3) 1alpha-hydroxylase (CYP27B1) gene through the leptin receptor (ObRb) by indirectly acting on the proximal tubules. This study focused on bone-derived fibroblast growth factor 23 (FGF-23) as a mediator of the influence of leptin on renal 1alpha-hydroxylase mRNA expression in leptin-deficient ob/ob mice. Exposure to leptin (200 ng/mL) for 24 hours stimulated FGF-23 expression by primary cultured rat osteoblasts. Administration of leptin (4 mg/kg i.p. at 12-hour intervals for 2 days) to ob/ob mice markedly increased the serum FGF-23 concentration while significantly reducing the serum levels of calcium, phosphate, and 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Administration of FGF-23 (5 microg i.p. at 12-hour intervals for 2 days) to ob/ob mice suppressed renal 1alpha-hydroxylase mRNA expression. The main site of FGF-23 mRNA expression was the bone, and leptin markedly increased the FGF-23 mRNA level in ob/ob mice. In addition, leptin significantly reduced 1alpha-hydroxylase and sodium-phosphate cotransporters (NaP(i)-IIa and NaP(i)-IIc) mRNA levels but did not affect Klotho mRNA expression in the kidneys of ob/ob mice. Furthermore, the serum FGF-23 level and renal expression of 1alpha-hydroxylase mRNA were not influenced by administration of leptin to leptin receptor-deficient (db/db) mice. These results indicate that leptin directly stimulates FGF-23 synthesis by bone cells in ob/ob mice, suggesting that inhibition of renal 1,25(OH)(2)D(3) synthesis in these mice is at least partly due to elevated bone production of FGF-23.

  4. Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration

    Directory of Open Access Journals (Sweden)

    José M. Rojas

    2017-04-01

    Full Text Available Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD and lipid inflammatory mediators ceramide 1-phosphate (C1P and lysophosphatidic acid (LPA, and the evaluation of their roles in monocyte migration. Recombinant rLlPLD1 (active and rLlPLD2 (inactive isoforms induce interleukin (IL-6, IL-8, CXCL1/GRO-α, and CCL2/monocyte chemoattractant protein-1 (MCP-1 expression and secretion in fibroblasts. Meanwhile, C1P and LPA only exhibited a minor effect on the expression and secretion of these cytokines and chemokines. Moreover, neutralization of both enzymes with anti-rLlPLD1 antibodies completely inhibited the secretion of these cytokines and chemokines. Importantly, conditioned media from fibroblasts, treated with rLlPLDs, stimulated the transmigration of THP-1 monocytes. Our data demonstrate the direct role of PLDs in chemotactic mediator synthesis for monocytes in human skin fibroblasts and indicate that inflammatory processes play an important role during loxoscelism.

  5. Alveolar macrophages stimulated with titanium dioxide, chrysotile asbestos, and residual oil fly ash upregulate the PDGF receptor-alpha on lung fibroblasts through an IL-1beta-dependent mechanism.

    Science.gov (United States)

    Lindroos, P M; Coin, P G; Badgett, A; Morgan, D L; Bonner, J C

    1997-03-01

    Enhanced proliferation of fibroblasts is a primary characteristic of lung fibrosis. Macrophage-secreted platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for lung fibroblasts. The magnitude of the fibroblast PDGF response is dependent on the number of PDGF receptor alpha (PDGF-R alpha) relative to PDGF-R beta at the cell surface. We recently reported that upregulation of the PDGF-R alpha subtype by interleukin (IL)-1beta results in enhanced lung fibroblast proliferation in response to PDGF-AA, PDGF-AB, and PDGF-BB whereas transforming growth factor (TGF)-beta1 has the opposite effect. Both IL-1beta and TGF-beta1 are produced by particle-activated macrophages in vivo and in vitro. We studied the net effect of macrophage conditioned medium (MOCM), which contains both IL-1beta and TGF-beta1, on the expression of the lung fibroblast PDGF receptor system. MOCM obtained from unstimulated, titanium dioxide (TiO2)-, chrysotile asbestos-, or residual oil fly ash (ROFA)-exposed macrophages in vitro increased [125I]PDGF-AA binding 3-, 6-, 6-, and 20-fold, respectively. These increases correlated with increased PDGF-R alpha mRNA and protein expression as shown by northern and western assays. PDGF-AB and -BB-stimulated [3H]thymidine incorporation by fibroblasts was enhanced 5-, 5-, 10-, and 20-fold by pretreatment with MOCM from unstimulated, TiO2-, asbestos-, and ROFA-exposed macrophages, respectively. [125I]PDGF-AA binding experiments using the IL-1 receptor antagonist blocked the upregulatory effect of all MOCM samples. Latent TGF-beta1 present in MOCM was activated by acid treatment, inhibiting upregulation by approximately 60%, a result similar to experiments with IL-1beta and TGF-beta1 mixtures. Treatment with a TGF-beta neutralizing antibody restored full upregulatory activity to acidified MOCM. Thus activated macrophages increase lung fibroblast PDGF-R alpha primarily due to the secretion of IL-1beta. Intratracheal instillation of ROFA

  6. Stimulation of 11β-HSD1 expression by IL-1β via a C/EBP binding site in human fetal lung fibroblasts.

    Science.gov (United States)

    Yang, Zhen; Zhu, Xiaoou; Guo, Chunming; Sun, Kang

    2009-12-01

    Proinflammatory cytokines, just like glucocorticoids (GCs), have been reported to upregulate 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression in many cell types. This concerted regulation of 11β-HSD1 by interleukin-1β (IL-1β) and GCs is in marked contrast to their antagonistic effects on inflammation. Further, the molecular mechanisms underlying the induction of 11β-HSD1 by IL-1β are not very well understood. In this study, we demonstrated that IL-1β dramatically stimulated 11β-HSD1 expression and enzyme activity as well as promoter activity including the -64 bp fragment upstream to the transcription start site in human fetal lung fibroblasts (HFL-1). Nucleotide mutations of the proximal CCAAT box within this region abolished the induction of 11β-HSD1 promoter activity by IL-1β. Western blotting analysis demonstrated that IL-1β induced the expression of C/EBPβ dramatically while C/EBPα was barely detectable in HFL-1 cells. Global inhibition of CCAAT/enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression plasmid (CMV500-A-C/EBP) significantly attenuated the induction of 11β-HSD1 by IL-1β, whereas over-expression of C/EBPβ enhanced the expression of 11β-HSD1. Chromatin immunoprecipitation assay revealed the recruitment of C/EBPβ to the promoter region containing the C/EBP binding site. In conclusion, IL-1β induces the expression of 11β-HSD1 mRNA in the fetal lung tissue through mechanisms that involve C/EBPβ binding to the promoter. This impact of IL-1β on the expression of 11β-HSD1 in human fetal lung cells may explain the alternate mechanism for the lung maturation that appears to occur when there is a risk of premature delivery of the fetus due to the presence of infection.

  7. Uterine Leiomyoma: Hysterosalpingographic Appearances

    Directory of Open Access Journals (Sweden)

    Firoozeh Ahmadi

    2008-01-01

    Full Text Available Uterine leiomyoma is the most common benign tumor of genital tract. The etiology of myomasis unknown. Leiomyoma shows a broad spectrum of radiographic appearances depending on thenumber, size, and location of the tumor. The diagnostic method for uterine leiomyomas is basedprimarily on the clinical situation. Despite of the varied diagnostic options such as; transvaginalsonography, sonohysterography, hysteroscopy, laparoscopy and MRI; hysterosalpingography isstill one of the valuable imaging methods for identification of uterine leiomyoma.The various features of the proved leiomyoma are illustrated in this pictorial review. The incidence,risk factors and clinical features will also be discussed briefly.

  8. Uterine primitive neuroectodermal tumor.

    Science.gov (United States)

    Aminimoghaddam, Soheila; Seifirad, Soroush; Abbasi Dezfouli, Golbahar; Abbasi, Neda; Zare Mehrjardi, Ali; Razavi, Seyed Mohsen; Mahmoudzadeh, Fatemeh

    2015-04-01

    Primitive neuroectodermal tumors are fairly rare in uterus. A case of uterine body primitive neuroectodermal tumor in a 32-year-old Iranian woman is presented. The patient was admitted with abdominal pain and fever and underwent emergency exploratory surgery with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. Posterior wall of the uterus was necrotic and ruptured and a huge tumor disrupted the uterine body. The tumor was strongly positive for CD99, NSE, and chromogranin; No reaction was seen for CD10, CD45 and myogenin. To the best of our knowledge, this is the first report of an uterine body primitive neuroectodermal tumor and the second report of uterine primitive neuroectodermal tumor from Iran.

  9. Uterine Cancer Statistics

    Science.gov (United States)

    ... Research AMIGAS Fighting Cervical Cancer Worldwide Stay Informed Statistics for Other Kinds of Cancer Breast Cervical Colorectal ( ... Skin Vaginal and Vulvar Cancer Home Uterine Cancer Statistics Language: English Español (Spanish) Recommend on Facebook Tweet ...

  10. Uterine Fibroid Embolization (UFE)

    Science.gov (United States)

    ... resembling coarse sand Gelfoam™, a gelatin sponge material microspheres, polyacrylamide spheres with a gelatin coating All of ... who wishes to have more children consider surgical removal of the individual tumors rather than undergo uterine ...

  11. Abnormal Uterine Bleeding FAQ

    Science.gov (United States)

    ... FREQUENTLY ASKED QUESTIONS FAQ095 GYNECOLOGIC PROBLEMS Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is abnormal bleeding more ...

  12. Spontaneous uterine rupture

    African Journals Online (AJOL)

    After ultrasound scan, uterine rupture was diagnosed and an ... delivery. The birth weights ranged between 2900 and 3200g. The last 2 .... abdominal pains and signs of shock, at which made up of altered blood and we think that the.

  13. Dysfunctional Uterine Bleeding

    OpenAIRE

    1987-01-01

    Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding that results from an ovarian endocrinopathy. It may be associated with ovulatory and anovulatory cycles. The diagnosis of DUB depends on a thorough history and physical examination to exclude organic disorders. In older women, endometrial biopsy should be done before starting therapy. The treatment depends on an understanding of the menstrual cycle. In less urgent cases, anovulatory cycles are managed using progester...

  14. The Clinical Research on Prevention Effects of Uterine Cavity Absorbed Biological Antiblocking Membrane Implantation plus Large Dose Estrogenic Administration plus Imitable Bioelectricity Stimulation Therapy for Uterine CavityAdhesion after TCRA%宫腔粘连分离术后宫腔放置可吸生物防粘连膜+大剂量雌激素+仿生物电疗预防再次粘连的临床研究

    Institute of Scientific and Technical Information of China (English)

    李艳虹; 梁晓斯; 林东红

    2016-01-01

    目的:探讨生物防粘连膜宫腔放置联合大剂量雌激素治疗,再给予仿生物电刺激治疗对宫腔粘连分离术后的再粘连防治的临床疗效。方法:选取2014年2月-2016年2月本院收治的经TCRA成功分离的中、重度宫腔粘连患者48例作为研究对象,随机分为观察组25例和对照组23例。观察组给予防粘连膜宫腔放置联合大剂量雌激素治疗,再给予仿生物电治疗,对照组则给予防粘连膜宫腔放置联合大剂量雌激素治疗,两组均以30 d为1个疗程,共进行3个疗程,B超检查子宫内膜修复程度。结果:治疗2个疗程后,两组子宫内膜均较治疗前增厚,且观察组优于对照组,比较差异均有统计学意义(P<0.05);观察组治疗总有效率为92.00%,明显高于对照组的56.52%,比较差异有统计学意义(P<0.05)。结论:防粘连膜宫腔放置联合大剂量雌激素治疗,再给予仿生物电刺激疗法能够有效防治宫腔粘连分离术后的再粘连。%Objective:To discuss the clinical effects of uterine cavity absorbed biological antiblocking membrane implantation plus large dose estrogenic administration plus imitable bioelectricity stimulation therapy for uterine cavity adhesion after TCRA.Method:From February 2014 to February 2016,48 cases of successfully separated by TCRA middle and severe uterine cavity adhesion in our hospital were selected as the research objects, they were randomly divided into the observation group of 25 cases and the control group of 23 cases.The observation group was given absorbed biological antiblocking membrane implantation plus large dose estrogenic administration plus imitable bioelectricity stimulation therapy,the control group was given absorbed biological antiblocking membrane implantation plus large dose estrogenic administration,two groups were treated with 30 d for 1 treatment course,a total of 3 courses,the degree of endometrial repair was inspected

  15. Dysfunctional Uterine Bleeding (DUB) (For Teens)

    Science.gov (United States)

    ... the Right Sport for You Shyness Abnormal Uterine Bleeding (AUB) KidsHealth > For Teens > Abnormal Uterine Bleeding (AUB) ... español Hemorragia uterina disfuncional What Is Abnormal Uterine Bleeding? Abnormal uterine bleeding (AUB) is the name doctors ...

  16. Vaginal or uterine bleeding - overview

    Science.gov (United States)

    There are many causes of abnormal vaginal bleeding. HORMONES Most often, abnormal uterine bleeding is caused by a hormone imbalance. When hormones are the cause, doctors call the problem dysfunctional uterine bleeding (DUB) . DUB is more ...

  17. The effect of cinnamon extract on isolated rat uterine strips.

    Science.gov (United States)

    Alotaibi, Mohammed

    2016-03-01

    Cinnamon is a spice used by some populations as a traditional remedy to control blood pressure and thus hypertension. Cinnamon extract decreases contractility in some smooth muscles, but its effect on uterine smooth muscle is unknown. The aim of this study was to determine the physiological and pharmacological effects of cinnamon extract (CE) on the contractions of isolated rat uterine strips and to investigate its possible mechanism of action. Isolated longitudinal uterine strips were dissected from non-pregnant rats, mounted vertically in an organ bath chamber, and exposed to different concentrations of CE (10-20mg/mL). The effect of CE was investigated in the presence of each of the following solutions: 60mM KCl, 5nM oxytocin, and 1μM Bay K8644. CE significantly decreased the force of uterine contraction in a concentration-dependent manner and significantly attenuated the uterine contractions elicited by KCl and oxytocin. In addition, CE significantly decreased the contractile force elicited when L-type Ca(2+) channels were activated by Bay K8644. CE's major mechanism may be inhibition of L-type Ca(2+) channels, which limits calcium influx. These data demonstrate that CE can be a potent tocolytic that can decrease uterine activity regardless of how the force was produced, even when the uterus was stimulated by agonists. As a result, cinnamon may be used to alleviate menstrual pain associated with dysmenorrhoea or prevent unwanted uterine activity in early pregnancy.

  18. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jaguin, Marie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex (France); Lecureur, Valérie, E-mail: valerie.lecureur@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France)

    2015-06-15

    Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.

  19. Uterine mesenchymal tumors

    Directory of Open Access Journals (Sweden)

    Nikhil A Sangle

    2011-01-01

    Full Text Available Uterine mesenchymal tumors are a heterogeneous group of neoplasms that can frequently be diagnostically challenging. Differentiation between the benign and malignant counterparts of mesenchymal tumors is significant due to differences in clinical outcome, and the role of the surgical pathologist in making this distinction (especially in the difficult cases cannot be underestimated. Although immunohistochemical stains are supportive toward establishing a final diagnosis, the morphologic features trump all the other ancillary techniques for this group of neoplasms. This review therefore emphasizes the key morphologic features required to diagnose and distinguish uterine mesenchymal tumors from their mimics, with a brief description of the relevant immunohistochemical features.

  20. Steroidal regulation of uterine resistance to bacterial infection in livestock

    Directory of Open Access Journals (Sweden)

    Lewis Gregory S

    2003-11-01

    Full Text Available Abstract Postpartum uterine infections reduce reproductive efficiency and have significant animal welfare and economic consequences. Postpartum uterine infections are classified as nonspecific, but Arcanobacterium pyogenes and Escherichia coli are usually associated with them in cattle and sheep. Pyometra is the most common type of uterine infection in dairy cattle, and it is detected almost exclusively in cows with active corpora lutea. Luteal progesterone typically down-regulates uterine immune functions and prevents the uterus from resisting infections. Progesterone also can down-regulate uterine eicosanoid synthesis. This seems to be a critical event in the onset of uterine infections, because eicosanoids can up-regulate immune cell functions in vitro. In addition, exogenous prostaglandin F2 alpha stimulates uterine secretion of prostaglandin F2 alpha and enhances immune functions in vivo. Thus, one may hypothesize that eicosanoids can override the negative effects of progesterone and that the up-regulatory effects of exogenous prostaglandin F2 alpha allow the uterus to resolve an infection, regardless of progesterone concentrations. Based on the results of studies to test that hypothesis, cows, sheep, and pigs in various physiological statuses are resistant to intrauterine infusions of Arcanobacterium pyogenes and Escherichia coli, unless progesterone concentrations are increased. In sheep and pigs, exogenous prostaglandin F2 alpha stimulates uterine production of prostaglandin F2 alpha and allows the uterus to resolve Arcanobacterium pyogenes-Escherichia coli-induced infections, even when progesterone is maintained at luteal phase concentrations before and after treatment. Prostaglandin F2 alpha is a proinflammatory molecule that stimulates the production of various proinflammatory cytokines, and it may enhance uterine production of leukotriene B4. Proinflammatory cytokines and leukotriene B4 enhance phagocytosis and lymphocyte functions

  1. Stimulation of fibroblast proliferation by neokyotorphin requires Ca influx and activation of PKA, CaMK II and MAPK/ERK.

    Science.gov (United States)

    Sazonova, Olga V; Blishchenko, Elena Yu; Tolmazova, Anna G; Khachin, Dmitry P; Leontiev, Konstantin V; Karelin, Andrey A; Ivanov, Vadim T

    2007-01-01

    Neokyotorphin [TSKYR, hemoglobin alpha-chain fragment (137-141)] has previously been shown to enhance fibroblast proliferation, its effect depending on cell density and serum level. Here we show the dependence of the effect of neokyotorphin on cell type and its correlation with the effect of protein kinase A (PKA) activator 8-Br-cAMP, but not the PKC activator 4beta-phorbol 12-myristate, 13-acetate (PMA). In L929 fibroblasts, the proliferative effect of neokyotorphin was suppressed by the Ca2+ L-type channel inhibitors verapamil or nifedipine, the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, kinase inhibitors H-89 (PKA), KN-62 (Ca2+/calmodulin-dependent kinase II) and PD98059 (mitogen-activated protein kinase). The proliferative effect of 8-Br-cAMP was also suppressed by KN-62 and PD98059. PKC suppression (downregulation with PMA or inhibition with bisindolylmaleimide XI) did not affect neokyotorphin action. The results obtained point to a cAMP-like action for neokyotorphin.

  2. [Electrotherapy and uterine fibroids].

    Science.gov (United States)

    Deroover, J

    2009-01-01

    At the end of the 19th century, uterine fibroids cause huge therapeutic issues: on the one hand they can reach an impressive massive volume; on the other hand they provoke endless haemorrhages. Dr Apostoli develops galvanotherapy which becomes the reference in French and international medicine before its rapid downfall as gynaecological surgery makes great progress at the beginning of the 20th Century.

  3. Uterine Fibroids Fact Sheet

    Science.gov (United States)

    ... uterus through the vagina, instead of making a cut in the abdomen. In some cases hysterectomy can ... into the blood vessels. This blocks the blood supply to the fibroid, causing it to shrink. UFE can be an outpatient ... warning on power morcellators in treatment for uterine fibroids If your ...

  4. Stimulation of chondrocytes in vitro by gene transfer with plasmids coding for epidermal growth factor (hEGF) and basic fibroblast growth factor (bFGF)

    DEFF Research Database (Denmark)

    Schmal, H; Mehlhorn, A T; Zwingmann, J

    2005-01-01

    Human epidermal growth factor (hEGF) and basic fibroblast growth factor (bFGF) influence critical characteristics of chondrocytes. The effects on metabolism and differentiation were evaluated following transfection using specific plasmids coding for both cytokines. Chondrocytes were isolated from...... of recombinant hEGF and bFGF resulted in a significant increase in cell proliferation and glucosaminoglycan production. Chondrocytes were transfected with vectors coding for either hEGF or bFGF and the production of these proteins was measured in supernatants by ELISA. Expression kinetics showed different...... patterns: hEGF was detectable 2.5 days following transfection and peaked at day 5.5, whereas bFGF-production reached its maximum 1.5 days after transfection, declining thereafter. Chondrocytes endogenously produced significant amounts of bFGF within 5 days following isolation. Proliferation of h...

  5. ENDOVASCULAR HEMOSTASIS IN UTERINE BLEEDING IN PATIENTS WITH UTERINE LEIOMYOMA

    Directory of Open Access Journals (Sweden)

    M. M. Damirov

    2017-01-01

    Full Text Available We report results of treatment for 72 patients with uterine leiomyoma (LM of various sizes and location, who had arrived with excessive uterine bleeding. All patients underwent urgent or urgently-delayed endovascular hemostasis by performing uterine arteries embolization (UAE. We analyzed clinical features of the disease after UAE in various sizes of tumors and studied immediate and long-term results of UAE in patients with LM.

  6. Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α).

    Science.gov (United States)

    Giotis, Efstathios S; Robey, Rebecca C; Skinner, Natalie G; Tomlinson, Christopher D; Goodbourn, Stephen; Skinner, Michael A

    2016-01-01

    Viruses that infect birds pose major threats-to the global supply of chicken, the major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza viruses H5N1 and H7N9). Controlling these viruses in birds as well as understanding their emergence into, and transmission amongst, humans will require considerable ingenuity and understanding of how different species defend themselves. The type I interferon-coordinated response constitutes the major antiviral innate defence. Although interferon was discovered in chicken cells, details of the response, particularly the identity of hundreds of stimulated genes, are far better described in mammals. Viruses induce interferon-stimulated genes but they also regulate the expression of many hundreds of cellular metabolic and structural genes to facilitate their replication. This study focusses on the potentially anti-viral genes by identifying those induced just by interferon in primary chick embryo fibroblasts. Three transcriptomic technologies were exploited: RNA-seq, a classical 3'-biased chicken microarray and a high density, "sense target", whole transcriptome chicken microarray, with each recognising 120-150 regulated genes (curated for duplication and incorrect assignment of some microarray probesets). Overall, the results are considered robust because 128 of the compiled, curated list of 193 regulated genes were detected by two, or more, of the technologies.

  7. Leiomyosarcoma: a rare malignant transformation of a uterine leiomyoma.

    Science.gov (United States)

    Di Luigi, G; D'Alfonso, A; Patacchiola, F; Di Stefano, L; Palermo, P; Carta, G

    2015-01-01

    The malignant transformation of a uterine leiomyoma is still debated and, if it occurs, it is very rare. The case of a patient affected by one small leiomyoma is described. Diagnosis was made postoperatively on histopathological examination. The case reported here is meant to underline the need to keep all uterine myomas in check since the transition into leiomyosarcomas (LMSs) may occur with an evolution over a time period which has not been established so far. Specific receptors for luteinizing hormone/human chorionic gonadotropin (LH/hCG) have also been identified in the myometrium of several animal species, including humans. Conventional LMSs express estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) in 30-40% of cases. In comparison with other more common uterine malignancies, uterine LMSs bear some resemblance to type 2 endometrial carcinomas and high-grade serous carcinomas of ovary/fallopian tube origin, based on their genetic instability, frequent p53 abnormalities, aggressive behavior, and resistance to chemotherapy. It could be useful to understand with further researches if hormonal stimulation could be a contributing factor of uterine leiomyoma transformation into LMS. Until today the oncogenic mechanisms underlying the development of uterine LMSs remain elusive.

  8. Development of a chemically defined in vitro culture system to effectively stimulate the proliferation of adult human dermal fibroblasts.

    Science.gov (United States)

    Kim, Min Seong; Yun, Jung Im; Gong, Seung Pyo; Ahn, Ji Yeon; Lim, Jeong Mook; Song, Young Han; Park, Kyu Hyun; Lee, Seung Tae

    2015-07-01

    Despite the fact that dermal fibroblasts are a practical model for research related to cell physiology and cell therapy, an in vitro culture system excluding serum, which complicates standardization and specificity and induces variability and unwanted effects, does not exist. We tried to establish a CDCS that supports effective proliferation of aHDFs. KDMEM supplemented with 5% (v/v) KSR, 12 ng/ml bFGF, 5 ng/ml EGF and 1 μg/ml hydrocortisone supported sufficient proliferation of aHDFs for 1 week. However, aHDF proliferation was decreased greatly after subculture. This problem could be overcome by culturing aHDFs in CDCM in culture plates coated with 10 μg/ml FN. Long-term culture of aHDFs was achieved using CDCM and FN-coated culture plates for 7 weeks. The optimized CDCS increased the proliferation of aHDFs significantly, without any increase in the senescence rate or alteration in morphology of aHDFs, despite long-term culture. In conclusion, we established a CDCS that improved proliferation of aHDFs while inhibiting cellular senescence. The CDCS will contribute to advances in various future research related to clinical skin regeneration.

  9. Uterine transplantation: a systematic review

    Science.gov (United States)

    Ejzenberg, Dani; Mendes, Luana Regina Baratelli Carelli; de Paiva Haddad, Luciana Bertocco; Baracat, Edmund Chada; D’Albuquerque, Luiz Augusto Carneiro; Andraus, Wellington

    2016-01-01

    Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women. PMID:27982170

  10. Uterine transplantation: a systematic review

    Directory of Open Access Journals (Sweden)

    Dani Ejzenberg

    Full Text Available Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

  11. Multiwalled carbon nanotubes induce a fibrogenic response by stimulating reactive oxygen species production, activating NF-κB signaling, and promoting fibroblast-to-myofibroblast transformation.

    Science.gov (United States)

    He, Xiaoqing; Young, Shih-Houng; Schwegler-Berry, Diane; Chisholm, William P; Fernback, Joseph E; Ma, Qiang

    2011-12-19

    Carbon nanotubes (CNTs) are novel materials with unique electronic and mechanical properties. The extremely small size, fiberlike shape, large surface area, and unique surface chemistry render their distinctive chemical and physical characteristics and raise potential hazards to humans. Several reports have shown that pulmonary exposure to CNTs caused inflammation and lung fibrosis in rodents. The molecular mechanisms that govern CNT lung toxicity remain largely unaddressed. Here, we report that multiwalled carbon nanotubes (MWCNTs) have potent, dose-dependent toxicity on cultured human lung cells (BEAS-2B, A549, and WI38-VA13). Mechanistic analyses were carried out at subtoxic doses (≤20 μg/mL, ≤ 24 h). MWCNTs induced substantial ROS production and mitochondrial damage, implicating oxidative stress in cellular damage by MWCNT. MWCNTs activated the NF-κB signaling pathway in macrophages (RAW264.7) to increase the secretion of a panel of cytokines and chemokines (TNFα, IL-1β, IL-6, IL-10, and MCP1) that promote inflammation. Activation of NF-κB involved rapid degradation of IκBα, nuclear accumulation of NF-κBp65, binding of NF-κB to specific DNA-binding sequences, and transactivation of target gene promoters. Finally, MWCNTs induced the production of profibrogenic growth factors TGFβ1 and PDGF from macrophages that function as paracrine signals to promote the transformation of lung fibroblasts (WI38-VA13) into myofibroblasts, a key step in the development of fibrosis. Our results revealed that MWCNTs elicit multiple and intertwining signaling events involving oxidative damage, inflammatory cytokine production, and myofibroblast transformation, which potentially underlie the toxicity and fibrosis in human lungs by MWCNTs.

  12. Treatment of uterine fibroids for abnormal uterine bleeding: myomectomy and uterine artery embolization.

    Science.gov (United States)

    Al-Mahrizi, Sharifa; Tulandi, Togas

    2007-12-01

    Uterine myoma is a common benign tumour in women and most cases do not require treatment. Excessive uterine bleeding is usually due to a submucous myoma or an intramural myoma that is encroaching into the uterine cavity. After eliminating endometrial malignancy, perimenopausal women could be managed expectantly or with gonadotrophin-releasing hormone agonist until menopause. Hysteroscopic myomectomy is highly effective in controlling menorrhagia that is related to submucous myoma. Concomitant endometrial ablation improves menorrhagia; however, the subsequent hysterectomy rate remains the same. For those with an intramural myoma, abdominal myomectomy results in good bleeding control. It could also be done by laparoscopic approach; however, the surgeon should have expertise in laparoscopic suturing and the uterine incision should be properly sutured. In women who have completed their family, hysterectomy remains the most effective treatment for excessive uterine bleeding. Compared with uterine artery embolization (UAE), it is associated with better improvement in pelvic pain. Nevertheless, UAE is a good alternative to hysterectomy.

  13. Uterine fibroid: a review.

    Science.gov (United States)

    Akinyemi, B O; Adewoye, B R; Fakoya, T A

    2004-01-01

    Uterine fibroid is a benign tumour of uterine smooth muscle. The purpose of this review is to bring to light the current spectra of presentation and management status of this benign and very important cause of menstrual and fertility disturbance in African women and the Black race in general. This is especially so with the trivialization of its aetological factors and treatment by claims from alternative medical practitioners. This review, therefore sought to document what is currently known about the condition and what could possibly be done to achieve better results in its management. Literature on the subject above was reviewed using manual library search, electronic books such as CD-ROMS and journals articles published by various local and international authors on the subject; it also included internet search on relevant aspects of the topic. Fibroid is the commonest benign tumour of the female genital tract, it contributes about 70 to 80% of new growths in the female genital tracts, it is a cause of significant morbidity in women of reproductive age group and when complicated could be a significant cause of mortality. Spectrum of presentation mainly involves disturbance of menstruation, reduction in fertility, pressure and obstructive symptoms and rarely malignant presentations. When recognized early effective conservative and definitive therapies are available to offer relief for women and to make their menstrual and reproductive life more meaningful. From the literature reviewed, it was obvious that the subject of uterine fibroid is still not fully exhausted and there were a lot of research questions waiting to be answered on the aetiopathogenesis of the disease. There is also the need to fashion out better treatment alternatives that will reduce morbidity in the process of managing the patient as well as those that will further enhance reproductive potentials after treatment.

  14. Lajjalu treatment of uterine prolapse

    Science.gov (United States)

    Shivanandaiah, T. M.; Indudhar, T. M.

    2010-01-01

    Mimosa pudica was found useful in cases of uterine prolapse with bleeding, consistent with my experience of working with the condition for more than 45 years, and treating hundreds of such cases of uterine prolapse. Hysterectomy has been avoided up to this date, and is not now expected to be recommended. PMID:21836800

  15. Lajjalu treatment of uterine prolapse

    Directory of Open Access Journals (Sweden)

    T M Shivanandaiah

    2010-01-01

    Full Text Available Mimosa pudica was found useful in cases of uterine prolapse with bleeding, consistent with my experience of working with the condition for more than 45 years, and treating hundreds of such cases of uterine prolapse. Hysterectomy has been avoided up to this date, and is not now expected to be recommended.

  16. Respiratory activity and growth of human skin derma fibroblasts.

    Science.gov (United States)

    Papa, F; Scacco, S; Vergari, R; Bucaria, V; Dioguardi, D; Papa, S

    1998-09-01

    A study has been made on the speed of growth and respiratory activity of fibroblast cultures from control derma, cheloid (hypertrophic) scar and stabilized scar taken from human skin. The speed of growth and the efficiency of plaque formation of fibroblasts from cheloid scar were greater in comparison with those of fibroblasts from stabilized scar and were stimulated by the addition to the culture medium of the exudate from post-traumatic ulcer. Measurement of the contents of cytochromes showed a decrease in the content of cytochromes b562 and c + c1 in the fibroblast culture from both cheloid and stabilized scar as compared to the fibroblast culture from control derma. Cytochrome aa3 content did not show significant difference among the three types of fibroblast cultures. The respiratory activities supported by pyruvate plus malate, succinate or ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine did not show, however, significant difference among the three fibroblast cultures. These observations show that the speed of growth of skin fibroblasts does not depend on the overall respiratory capacity. The exudate stimulated the activity of cytochrome c oxidase in fibroblasts from control derma, and cheloid scar. This effect and the accompanying stimulation of fibroblast growth might be correlated with the balance of oxygen free radicals.

  17. Hematopoietic Stem Cell Cytokines and Fibroblast Growth factor-2 Stimulate Human Endothelial Cell-Pericyte Tube Co-Assembly in 3D Fibrin Matrices under Serum-Free Defined Conditions

    Science.gov (United States)

    Smith, Annie O.; Bowers, Stephanie L. K.; Stratman, Amber N.; Davis, George E.

    2013-01-01

    We describe a novel 3D fibrin matrix model using recombinant hematopoietic stem cell cytokines under serum-free defined conditions which promotes the assembly of human endothelial cell (EC) tubes with co-associated pericytes. Individual ECs and pericytes are randomly mixed together and EC tubes form that is accompanied by pericyte recruitment to the EC tube abluminal surface over a 3-5 day period. These morphogenic processes are stimulated by a combination of the hematopoietic stem cell cytokines, stem cell factor, interleukin-3, stromal derived factor-1α, and Flt-3 ligand which are added in conjunction with fibroblast growth factor (FGF)-2 into the fibrin matrix. In contrast, this tube morphogenic response does not occur under serum-free defined conditions when VEGF and FGF-2 are added together in the fibrin matrices. We recently demonstrated that VEGF and FGF-2 are able to prime EC tube morphogenic responses (i.e. added overnight prior to the morphogenic assay) to hematopoietic stem cell cytokines in collagen matrices and, interestingly, they also prime EC tube morphogenesis in 3D fibrin matrices. EC-pericyte interactions in 3D fibrin matrices leads to marked vascular basement membrane assembly as demonstrated using immunofluorescence and transmission electron microscopy. Furthermore, we show that hematopoietic stem cell cytokines and pericytes stimulate EC sprouting in fibrin matrices in a manner dependent on the α5β1 integrin. This novel co-culture system, under serum-free defined conditions, allows for a molecular analysis of EC tube assembly, pericyte recruitment and maturation events in a critical ECM environment (i.e. fibrin matrices) that regulates angiogenic events in postnatal life. PMID:24391990

  18. Toll-like receptor 9 mediated responses in cardiac fibroblasts.

    Directory of Open Access Journals (Sweden)

    Ingrid Kristine Ohm

    Full Text Available Altered cardiac Toll-like receptor 9 (TLR9 signaling is important in several experimental cardiovascular disorders. These studies have predominantly focused on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently been attributed increasing significance in mediating inflammatory signaling. However, putative TLR9-signaling through cardiac fibroblasts remains non-investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts and investigate the consequence of such receptor activity on classical cardiac fibroblast cellular functions. Cultivated murine cardiac fibroblasts were stimulated with different TLR9 agonists (CpG A, B and C and assayed for the secretion of inflammatory cytokines (tumor necrosis factor α [TNFα], CXCL2 and interferon α/β. Expression of functional cardiac fibroblast TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and TNFα-release. These responses were TLR9-specific as complete inhibition of receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist (ODN 2088 or chloroquine diphosphate. TLR9-stimulated responses were also found more potent in cardiac fibroblasts when compared with classical innate immune cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate migration and proliferation, but did not influence myofibroblast differentiation in vitro. Finally, results from in vivo TLR9-stimulation with subsequent fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells, CD31+ cells and cardiac fibroblast-enriched cell-fractions corroborated our in vitro data and provided evidence of differentiated cell-specific cardiac responses. Thus, we conclude that cardiac fibroblast may constitute a significant TLR9 responder cell within the myocardium and, further, that such receptor activity may impact important cardiac fibroblast cellular functions.

  19. Uterine Contraction Modeling and Simulation

    Science.gov (United States)

    Liu, Miao; Belfore, Lee A.; Shen, Yuzhong; Scerbo, Mark W.

    2010-01-01

    Building a training system for medical personnel to properly interpret fetal heart rate tracing requires developing accurate models that can relate various signal patterns to certain pathologies. In addition to modeling the fetal heart rate signal itself, the change of uterine pressure that bears strong relation to fetal heart rate and provides indications of maternal and fetal status should also be considered. In this work, we have developed a group of parametric models to simulate uterine contractions during labor and delivery. Through analysis of real patient records, we propose to model uterine contraction signals by three major components: regular contractions, impulsive noise caused by fetal movements, and low amplitude noise invoked by maternal breathing and measuring apparatus. The regular contractions are modeled by an asymmetric generalized Gaussian function and least squares estimation is used to compute the parameter values of the asymmetric generalized Gaussian function based on uterine contractions of real patients. Regular contractions are detected based on thresholding and derivative analysis of uterine contractions. Impulsive noise caused by fetal movements and low amplitude noise by maternal breathing and measuring apparatus are modeled by rational polynomial functions and Perlin noise, respectively. Experiment results show the synthesized uterine contractions can mimic the real uterine contractions realistically, demonstrating the effectiveness of the proposed algorithm.

  20. [Uterine defibrillation in uterine inertia. Report of 2 cases].

    Science.gov (United States)

    Viñals, F; Correa, G; Quiroz, V

    1993-01-01

    The uterine atony are the most common cause of postpartum hemorrhage. Manual compression and pharmacologic methods are usually used with a successful result. When pharmacologic methods fail to control hemorrhage from atony, surgical measures should be undertaken to arrest the bleeding before it becomes life-threatening. We presents the utilization of electrical uterine defibrillation in two cases with acute hemorrhage confirming the effectivity of the proceeding.

  1. Ge-Gen Decoction attenuates oxytocin-induced uterine contraction and writhing response: potential application in primary dysmenorrhea therapy.

    Science.gov (United States)

    Yang, Lu; Chai, Cheng-Zhi; Yue, Xin-Yi; Yan, Yan; Kou, Jun-Ping; Cao, Zheng-Yu; Yu, Bo-Yang

    2016-02-01

    The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea (PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction (GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F2 alpha (PGF2α) and Ca(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF2α and Ca(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.

  2. Uterine arterial embolization for uterine leiomyoma: efficacy and clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Seon; Lee, Do Yon; Kim, Yong Tae; Park, Ki Hyun; Park, Yong Won; Cho, Jae Sung; Kim, Myung Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of); Won, Je Hwan [Ajou Univ. College of Medicine, Suwon (Korea, Republic of); Kang, Byung Chul [Ewha Womans Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-09-01

    To determine the efficacy and clinical outcome of uterine arterial embolization as a new approach to the management of uterine leiomyomas. Uterine arterial embolization was performed in 21 patients aged 26-62(mean, 42) years. Twenty of these had menorrhagia, dysmenorrhea, and mass-related symptoms (low abdominal discomfort, backache, urinary frequency, etc.) and one was diagnosed incidentally. Bilateral uterine arteries were selected individually and polyvinyl alcohol and/or gelfoam was used as an embolic material. Nineteen patients were followed up after embolization. Seventeen (89.5 %)reported satisfactory improvement of symptoms and follow-up sonography three months later showed a 58.5 % reduction in mean myoma volume. In 17 patients (89.5 %), the menstrual cycle returned to normal. All patients experienced pain after the procedure and other complications were vaginal bleeding (26.3 %) and fever (23.8 %). Uterine arterial embolization represents a new approach to the management of uterine leiomyoma-related symptoms. Further investigations and long-term follow-up are, however, enquired.

  3. Uterine/Endometrial Cancer: Chemotherapy

    Science.gov (United States)

    ... Types of Gynecologic Cancers Uterine/Endometrial Cancer Chemotherapy Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for endometrial cancer is usually given intravenously (injected ...

  4. Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model.

    Science.gov (United States)

    Gao, Yang; Li, Shu; Li, Qinglei

    2014-08-01

    In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-β (TGF-β) signaling is a fundamental regulator of diverse biological processes and is indispensable for multiple reproductive functions. However, the in vivo role of TGF-β signaling in uterine epithelial cells remains poorly defined. We have shown that in the uterus, conditional deletion of the Type 1 receptor for TGF-β (Tgfbr1) using anti-Müllerian hormone receptor type 2 (Amhr2) Cre leads to myometrial defects. Here, we describe enhanced epithelial cell proliferation by immunostaining of Ki67 in the uteri of these mice. The aberration culminated in endometrial hyperplasia in aged females. To exclude the potential influence of ovarian steroid hormones, the proliferative status of uterine epithelial cells was assessed following ovariectomy. Increased uterine epithelial cell proliferation was also revealed in ovariectomized Tgfbr1 Amhr2-Cre conditional knockout mice. We further demonstrated that transcript levels for fibroblast growth factor 10 (Fgf10) were markedly up-regulated in Tgfbr1 Amhr2-Cre conditional knockout uteri. Consistently, treatment of primary uterine stromal cells with TGF-β1 significantly reduced Fgf10 mRNA expression. Thus, our findings suggest a potential involvement of TGFBR1-mediated signaling in the regulation of uterine epithelial cell proliferation, and provide genetic evidence supporting the role of uterine epithelial cell proliferation in the pathogenesis of endometrial hyperplasia.

  5. Sterility of the uterine cavity

    DEFF Research Database (Denmark)

    Møller, Birger R.; Kristiansen, Frank V.; Thorsen, Poul

    1995-01-01

    from the same sites. Nearly a quarter of all the patients harbored one or more microorganisms in the uterus, mostly Gardnerella vaginalis, Enterobacter and Streptococcus agalactiae. We found that in a significant number of cases, the uterine cavity is colonized with potentially pathogenic organisms...... which may play a causative role in endometritis. The results indicate that inflammation of the uterine cavity should be evaluated by hysteroscopic examination before hysterectomy is undertaken in patients with persistent irregular vaginal bleeding. Udgivelsesdato: 1995-Mar...

  6. Postpartum uterine health in cattle.

    Science.gov (United States)

    Sheldon, I M; Dobson, H

    2004-07-01

    Uterine health is often compromised in cattle because postpartum contamination of the uterine lumen by bacteria is ubiquitous, and pathogenic bacteria frequently persist causing clinical disease. The subfertility associated with uterine infection involves perturbation of the hypothalamus, pituitary and ovary, in addition to the direct effects on the uterus, and appears to persist even after clinical resolution of the disease. Absorption of bacterial components from the uterus can prevent the follicular phase LH surge and ovulation. In addition, the first postpartum dominant follicle has a slower growth rate and secretes less estradiol at the end of the growth phase. There are also localised ovarian effects of high uterine bacterial growth density, because fewer first dominant follicles are selected in the ovary ipsilateral than contralateral to the previously gravid uterine horn. Thus, it is important to diagnose and treat uterine disease promptly and effectively. Examination of the contents of the vagina for the presence of pus is the most useful method for diagnosis of endometritis. The character and odor of the vaginal mucus can be scored and this endometritis score is correlated with the growth density of pathogenic bacteria in the uterus, and is prognostic for the likely success of treatment. The challenge for the future is to design prevention and control programs to reduce the incidence of disease, and understand how the immune and endocrine systems are integrated.

  7. New procedures for uterine prolapse.

    Science.gov (United States)

    Khunda, Azar; Vashisht, Arvind; Cutner, Alfred

    2013-06-01

    Traditionally, vaginal hysterectomy and Manchester repair were the surgical approaches to treating uterine prolapse; however, both are associated with a relatively high subsequent vaginal vault recurrence. Laparoscopic uterine suspension is a new way of maintaining uterine support. Many women are keen to keep their uterus for a variety of reasons, including maintaining reproductive capability and the belief that the uterus, cervix, or both, may play a part of their gender identity. Non-removal of the uterus may retain functional (e.g. bowel, bladder and sexual) benefits. Therefore, the concept of uterine preservation for pelvic-organ prolapse has been of interest to pelvic-floor surgeons for many decades. In this review, we provide an overview of the available evidence on treating uterine prolapse surgically. We describe techniques to support the vault during hysterectomy, and examine the evidence for uterine-sparing surgery. Comparative outcomes for vaginal, abdominal and laparoscopic routes will be made. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Clinical observation of Pelvic floor electrical stimulation and biofeedback combined with buzhongyiqi decoction in the treatment of Qi -blood deficiency type uterine prolapse%盆底电刺激+生物反馈结合补中益气汤治疗气血虚弱型子宫脱垂的临床观察

    Institute of Scientific and Technical Information of China (English)

    谭快玲

    2014-01-01

    Objective To investigate the clinical effect of pelvic electric stimulation plus biofeedback combined with buzhongyiqi decoction in the treatment of Qi -blood deficiency type uterine prolapse .Methods 150 cases of Qi-blood deficiency type uterine prolapse patients , got therapy in our hospital during March 2010 and March 2013, were randomly divided into A, B and C group, 50 cases in each group.They were treated with three different methods respectively: buzhongyiqi decoction and Pelvic floor Kegel exercises , biofeedback and pelvic floor stimulation and Pelvic floor Kegel exercises , pelvic electric stimulation and biofeedback combined with buzhongyiqi decoction .Compared the total efficacy and vaginal muscle voltage .Results Total effective rate of group C (88%) was significantly higher than those of group A (52%) and group B (56%), the differences were statistically significant ( P 0.05 ).Compared with the vaginal muscle voltage before the treatment , differences were statistically significant ( P <0.01), and the differences between group C and group A/B were statistically significant (P<0.05).Conclusions The application of pelvic electric stimulation plus biofeedback combined with buzhongyiqi decoction achieved significant efficacy in the treatment of uterine prolapse , and vaginal muscle voltage changes significantly , it's worth of popularized and applied in clinic .%目的:探讨盆底电刺激+生物反馈结合补中益气汤治疗气血虚弱型子宫脱垂的临床效果。方法将2010年3月至2013年3月在我院门诊就医的150例气血虚弱型轻中度子宫脱垂患者随机分为A、B、C三组,各为50例,分别给予补中益气汤+盆底凯格尔运动、盆底电刺激+生物反馈+盆底凯格尔运动、盆底电刺激+生物反馈结合补中益气汤对其进行治疗,比较三组临床治疗总有效率及治疗前后阴道肌电压。结果 A、B、C三组治疗总有效率分别为52.00%、56.00%、88.00

  9. The etiopathogenesis of uterine fibromatosis

    Science.gov (United States)

    Manta, L; Suciu, N; Toader, O; Purcărea, RM; Constantin, A; Popa, F

    2016-01-01

    Uterine fibroids or uterine leiomyomas are the most common benign tumors of the uterus among women of fertile age, while the etiology is still incompletely elucidated. The occurrence and development of the fibromatosis may be related to certain risk factors and genic mechanisms, although the exact causes are not yet fully known. The development of uterine fibroids is correlated not only with the metabolism and with the level of female sexual hormones, estrogen, and progesterone, but also with the number of these hormone receptors expressed on the surface of the myometrium. Proliferative effects of estrogen and progesterone may be exercised through proinflammatory factors (TNF alpha), growth factors (IGF1, IGF2, TGFbeta3 and betaFGF) or inhibitors of apoptosis (p53 suppression). A number of predisposing factors such as ethnicity – black skin, early menarche, nulliparity, caffeine and alcohol, chronic inflammation, obesity, were also identified. Approximately 40% of the uterine fibroids are caused by the same cytogenetic alterations found in the other tumor types such as kidney, lung, or leiomyosarcoma. As part of a system dysfunction, uterine fibromatosis was connected to other disorders such as AHT (arterial hypertension), endometrium adenocarcinoma, adenomyosis, endometriosis, diabetes mellitus, breast tumors, seemingly with a common causality. The action and effect of some hormonal imbalances over the various organs depend on the histological and local expression particularities of the various receptors, being the cause for many disorders, among which the uterine fibromatosis, coexisting or accompanying the later. This article examines and summarizes the latest data refreshed literature etiopathogenesis offering indicators of uterine fibroids. PMID:27974911

  10. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    Science.gov (United States)

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

  11. TEAD1 inhibits prolactin gene expression in cultured human uterine decidual cells1

    OpenAIRE

    Kessler, Cherie A.; Bachurski, Cindy J.; Schroeder, Jennifer; Stanek, Jerzy; Handwerger, Stuart

    2008-01-01

    Forced overexpression of TEAD1 in human uterine fibroblast (HUF) and human endometrial stromal cells markedly inhibited prolactin promoter activity in both cell types in a dose-dependent manner, with maximal inhibition of greater than 90%. Conversely, the knockdown of TEAD1 expression in HUF cells with a TEAD1 siRNA resulted in a 75–80% increase in prolactin mRNA levels (P

  12. Pregnancy after uterine arterial embolization

    Directory of Open Access Journals (Sweden)

    Cláudio E. Bonduki

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate pregnancy outcomes, complications and neonatal outcomes in women who had previously undergone uterine arterial embolization. METHODS: A retrospective study of 187 patients treated with uterine arterial embolization for symptomatic uterine fibroids between 2005-2008 was performed. Uterine arterial embolization was performed using polyvinyl alcohol particles (500-900 mm in diameter. Pregnancies were identified using screening questionnaires and the study database. RESULTS: There were 15 spontaneous pregnancies. Of these, 12.5% were miscarriages (n = 2, and 87.5% were successful live births (n = 14. The gestation time for the pregnancies with successful live births ranged from 36 to 39.2 weeks. The mean time between embolization and conception was 23.8 months (range, 5-54. One of the pregnancies resulted in twins. The newborn weights (n = 14 ranged from 2.260 to 3.605 kg (mean, 3.072 kg. One (7.1% was considered to have a low birth weight (2.260 kg. There were two cases of placenta accreta (12.5%, treated with hysterectomy in one case [6.3%], one case of premature rupture of the membranes (PRM (6.3%, and one case of preeclampsia (6.3%. All of the patients were delivered via Cesarean section. CONCLUSION: In this study, there was an increased risk of Cesarean delivery. There were no other major obstetric risks, suggesting that pregnancy after uterine arterial embolization is possible without significant morbidity or mortality.

  13. Pregnancy with asymptomatic uterine complete rupture after uterine artery embolization for postpartum hemorrhage

    Directory of Open Access Journals (Sweden)

    Hiroaki Soyama

    2017-08-01

    Conclusion: Many studies have been reported that uterine artery embolization for postpartum hemorrhage did not affect subsequent pregnancy outcomes. However, we report that this procedure contains a potential risk for asymptomatic uterine rupture in a subsequent pregnancy. Although it is difficult to diagnose uterine rupture without symptoms, the obstetrician should be aware of the possibility of uterine rupture.

  14. Enhanced myometrial autophagy in postpartum uterine involution

    Directory of Open Access Journals (Sweden)

    Keng-Fu Hsu

    2014-09-01

    Conclusion: Autophagy of myocytes may play an important role in uterine involution. These results have implications for our understanding of myometrial functional adaptations during pregnancy and the physiological role of autophagy in the uterine remodeling events in the postpartum period.

  15. Treatment Options by Stage (Uterine Sarcoma)

    Science.gov (United States)

    ... Cancer Prevention Endometrial Cancer Screening Research Uterine Sarcoma Treatment (PDQ®)–Patient Version General Information About Uterine Sarcoma ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  16. Does coupling ofuterine contractions reflect uterine dysfunction?

    African Journals Online (AJOL)

    spontaneous nonnal labour at tenn were divided into two groups ... irregular uterine contractions during labour occurred ... Oxytocin was administered when the uterine activity was less than .... Greater cervical dilatation at the onset of labour in.

  17. N-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.

    LENUS (Irish Health Repository)

    Burke, John P

    2012-02-01

    BACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn\\'s disease (CD). Transforming growth factor-beta (TGF-beta) is important in fibroblast activation, while cell attachment and migration is regulated by the adhesion molecule N-cadherin. The aim of this study was to investigate the expression and function of N-cadherin in intestinal fibroblasts in patients with fibrostenosing CD. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies from patients undergoing resection for terminal ileal fibrostenosing CD (n = 14) or controls patients (n = 8). N-cadherin expression was assessed using Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fibroblasts were stimulated with TGF-beta and selective pathway inhibitors Y27632, PD98050, and LY294002 were used to examine the Rho\\/ROCK, ERK-1\\/2, and Akt signaling pathways, respectively. Cell migration was assessed using a scratch wound assay. N-cadherin was selectively overexpressed using a plasmid. RESULTS: Fibroblasts from fibrostenosing CD express increased constitutive N-cadherin mRNA and protein and exhibit enhanced basal cell migration relative to those from directly adjacent normal bowel. Control fibroblasts treated with TGF-beta induced N-cadherin in a dose-dependent manner which was inhibited by Rho\\/ROCK and Akt pathway modulation. Control fibroblasts exhibited enhanced cell migration in response to treatment with TGF-beta or transfection with an N-cadherin plasmid. CONCLUSIONS: Fibroblasts from strictures in CD express increased constitutive N-cadherin and exhibit enhanced basal cell migration. TGF-beta is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-beta-mediated induction of N-cadherin may potentiate Crohn\\'s stricture formation.

  18. Infertility and uterine fibroids.

    Science.gov (United States)

    Zepiridis, Leonidas I; Grimbizis, Grigoris F; Tarlatzis, Basil C

    2016-07-01

    Uterine fibroids are the most common tumors in women and their prevalence is higher in patients with infertility. At present, they are classified according to their anatomical location, as no classification system includes additional parameters such as their size or number. There is a general agreement that submucosal fibroids negatively affect fertility, when compared to women without fibroids. Intramural fibroids above a certain size (>4 cm), even without cavity distortion, may also negatively influence fertility. However, the presence of subserosal myomas has little or no effect on fertility. Many possible theories have been proposed to explain how fibroids impair fertility: mechanisms involving alteration of local anatomical location, others involving functional changes of the myometrium and endometrium, and finally endocrine and paracrine molecular mechanisms. Nevertheless, any of the above mentioned mechanisms can cause reduced reproductive potential, thereby leading to impaired gamete transport, reduced ability for embryo implantation, and creation of a hostile environment. The published experience defines the best practice strategy, as not many large, well-designed, and properly powered studies are available. Myomectomy appears to have an effect in fertility improvement in certain cases. Excision of submucosal myomas seems to restore fertility with pregnancy rates after surgery similar to normal controls. Removal of intramural myomas affecting pregnancy outcome seems to be associated with higher pregnancy rates when compared to non-operated controls, although evidence is still nοt sufficient. Treatment of subserosal myomas of reasonable size is not necessary for fertility reasons. The results of endoscopic and open myomectomy are similar; thus, endoscopic treatment is the recommended approach due to its advantages in patient's postoperative course.

  19. Effect of granulocyte/macrophage colony-stimulating factor on expression of vascular endotllelial growth factor in human dermal fibroblasts%粒细胞-单核巨噬细胞集落刺激因子对人皮肤成纤维细胞血管内皮细胞生长因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    李晓光; 方勇; 姚敏; 徐鹏; 俞为荣; 倪涛; 王莹

    2011-01-01

    Objective To study the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on the expression of vascular endotllelial growth factor (VEGF) in human dermal fibroblast. Methods In vitro human dermal fibroblasts in good status were incubated with GM-CSF (GM-CSF group) or non-GM-CSF (control group) culture medium for different periods of time. The mRNA, protein expression of VEGF in derma fibroblast were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, and the secretion of VEGF in supernatant was measured by enzyme linked immunosorbant assay (ELISA). Results The expression of VEGF mRNA from dermal fibroblasts was increased significantly after l or more hours of incubation with GM-CSF comparing with the control (P<0.05). 6 hours of stimulation by GM-CSF caused maximal expression of VEGF mRNA. The expression of VEGF protein in dermal fibroblasts was increased from 12 hours and was peaked at 24 hour after stimulation by GM-CSF. VEGF protein from the supernatant of the dermal fibroblasts was also raised persistently from 12 hour after stimulation by GM-CSF and was improved remarkably compared with the control. Conclusions GM-CSF can up-regulate directly the expression of VEGF in human derma fibroblast, which may be one of the mechanisms that GM-CSF accelerates neovascularization in wound healing.%目的 探讨粒细胞-单核巨噬细胞集落刺激因子(granulocyte-macrophage colony stimulating factor,GM-CSF)对人皮肤成纤维细胞血管内皮细胞生长因子(vascular endothelial cell growth factor,VEGF)表达的影响.方法 分别用含GM-CSF(GM-CSF组)和不含GM-CSF(对照组)培养液,孵育离体培养的人皮肤成纤维细胞,作用不同时间后,采用逆转录-聚合酶链反应(RT-PCR)、蛋白质印迹法(Western印迹法)、酶联免疫吸附试验(ELISA)分别检测人皮肤成纤维细胞VEGF mRNA表达和蛋白表达.结果 GM-CSF作用1、3、6、12 h后,人皮肤成纤

  20. Oral fibroblasts produce more HGF and KGF than skin fibroblasts in response to co-culture with keratinocytes

    DEFF Research Database (Denmark)

    Grøn, Birgitte; Stoltze, Kaj; Andersson, Anders

    2002-01-01

    The production of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in subepithelial fibroblasts from buccal mucosa, periodontal ligament, and skin was determined after co-culture with keratinocytes. The purpose was to detect differences between the fibroblast subpopulations...... that could explain regional variation in epithelial growth and wound healing. Normal human fibroblasts were cultured on polystyrene or maintained in collagen matrix and stimulated with keratinocytes cultured on membranes. The amount of HGF and KGF protein in the culture medium was determined every 24 h for 5...... days by ELISA. When cultured on polystyrene, the constitutive level of KGF and HGF in periodontal fibroblasts was higher than the level in buccal and skin fibroblasts. In the presence of keratinocytes, all three types of fibroblasts in general increased their HGF and KGF production 2-3 times. When...

  1. Uterine prolapse in a primigravid woman.

    Science.gov (United States)

    Kim, Jeong Ok; Jang, Shin A; Lee, Ji Yeon; Yun, Nae Ri; Lee, Sang-Hun; Hwang, Sung Ook

    2016-05-01

    Uterine prolapse during pregnancy is an uncommon condition. It can cause preterm labor, spontaneous abortion, fetal demise, maternal urinary complication, maternal sepsis and death. We report the case of uterine prolapse in a 32-year-old healthy primigravid woman. She had no risk factors associated with uterine prolapse. She was conservatively treated, resulting in a successful vaginal delivery. This report is a very rare case of uterine prolapse in a young healthy primigravid woman, resulting in a successful vaginal delivery.

  2. First Trimester Spontaneous Uterine Rupture in a Young Woman with Uterine Anomaly

    Directory of Open Access Journals (Sweden)

    Esra Nur Tola

    2014-01-01

    Full Text Available Spontaneous uterine rupture is a life-threatening obstetrical emergency carrying a high risk for the mother and the fetus. Spontaneous uterine rupture in early pregnancy is very rare complication and it occurs usually in scarred uterus. Uterine anomalies are one of the reasons for spontaneous unscarred uterine rupture in early pregnancy. Obstetricians must consider this diagnosis when a pregnant patient presented with acute abdomen in early pregnancy. We present a case of spontaneous uterine rupture at 12 weeks of gestation in 24-year-old multigravida who had uterine anomaly presenting as an acute abdomen. Our preoperative diagnosis was ectopic pregnancy. Emergency laparotomy confirmed a spontaneous uterine rupture. Uterine anomaly is a risk factor for spontaneous uterine rupture in the early pregnancy. Clinical signs of uterine rupture in early pregnancy are nonspecific and must be distinguished from acute abdominal emergencies.

  3. [Effect of D-(-)-norgestrel on uterine contractility in the puerperium (author's transl)].

    Science.gov (United States)

    Romero-Salinas, G; La Torre-Rasguido, F; Vera-Cáceres, R; Escalera-Villarreal, G; Bandera-Gonzalez, B

    1981-01-01

    It is usual for women to ask for temporary control of fertility during the puerperium. When hormonal therapy is administered, the selection of the adequate pill is very important. The effect of D-(-)-norgestrel 300mg was studied on uterine contractility values during puerperium is seven patients breast feeding and was compared with a control group of 26. The 33 patients had the following characteristics: multiparous during puerperium without recent episiotomy, with healthy cervix, absence of genital septic focus, uterine tumours or malformations; all of them breast feeding. In the hypothesis, it was considered that the endogenous oxytocin increases and stimulates the mammary mioepithelium and uterine contractilities. For recording uterine contractility, the technique of Jaumandreu and Hendricks was used. The recordings were made during 24 hours postpartum, and at 5, 10, 20, 30, and 40 days with a duration 2 to 3 hours. All the studies were longitudinal. The changes of the human uterine contractility during normal puerperium were estimated. The range of the tonus was 22--41 mm Hg, the intensity 5--18 mm Hg, the frequency 17--23 contractions in 10 minutes, and the uterine activity 102--223 Montevideo Units. In the control group the following results were obtained: The range of the tonus was 24--34 mm Hg, the intensity 9--16 mm Hg, the frequency 17--37 contractions in 10 minutes, and the uterine contractility 137--524 Montevideo Units. In the comparative study Student's t test was used and p estimated.

  4. Uterine contraction induced by Ghanaian plants used to induce abortion

    DEFF Research Database (Denmark)

    Larsen, Birgitte HV; Soelberg, Jens; Kristiansen, Uffe

    2016-01-01

    Ethnomedicinal observations from the time of the Atlantic slave trade show women in Ghana historically used plants as emmenagogues (menstruation stimulants) and to induce abortion. This study investigates the effect of four of these plants on uterine contraction. The historically used plants were...... response obtained with acetylcholine. Erythrina senegalensis, Ficus sur and Physalis angulata did not show activity. M. cecropioides can thus be used to induce contractions, which coincides well with the historical and extant use of M. cecropioides as emmenagogue/birth stimulant...

  5. Quiescent and proliferative fibroblasts exhibit differential p300 HAT activation through control of 5-methoxytryptophan production.

    Directory of Open Access Journals (Sweden)

    Huei-Hsuan Cheng

    Full Text Available Quiescent fibroblasts possess unique genetic program and exhibit high metabolic activity distinct from proliferative fibroblasts. In response to inflammatory stimulation, quiescent fibroblasts are more active in expressing cyclooxygenase-2 and other proinflammatory genes than proliferative fibroblasts. The underlying transcriptional mechanism is unclear. Here we show that phorbol 12-myristate 13-acetate (PMA and cytokines increased p300 histone acetyltransferase activity to a higher magnitude (> 2 fold in quiescent fibroblasts than in proliferative fibroblasts. Binding of p300 to cyclooxygenase-2 promoter was reduced in proliferative fibroblasts. By ultrahigh-performance liquid chromatography coupled with a quadrupole time of flight mass spectrometer and enzyme-immunoassay, we found that production of 5-methoxytryptophan was 2-3 folds higher in proliferative fibroblasts than that in quiescent fibroblasts. Addition of 5-methoxytryptophan and its metabolic precursor, 5-hydroxytryptophan, to quiescent fibroblasts suppressed PMA-induced p300 histone acetyltransferase activity and cyclooxygenase-2 expression to the level of proliferative fibroblasts. Silencing of tryptophan hydroxylase-1 or hydroxyindole O-methyltransferase in proliferative fibroblasts with siRNA resulted in elevation of PMA-induced p300 histone acetyltransferase activity to the level of that in quiescent fibroblasts, which was rescued by addition of 5-hydroxytryptophan or 5-methoxytryptophan. Our findings indicate that robust inflammatory gene expression in quiescent fibroblasts vs. proliferative fibroblasts is attributed to uncontrolled p300 histone acetyltransferase activation due to deficiency of 5-methoxytryptophan production. 5-methoxytryptophan thus is a potential valuable lead compound for new anti-inflammatory drug development.

  6. Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection.

    Science.gov (United States)

    Fang, L; Nowicki, B; Yallampalli, C

    2001-05-01

    Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and

  7. Triiodothyronine (T3)-associated upregulation and downregulation of nuclear T3 binding in the human fibroblast cell (MRC-5)--stimulation of malic enzyme, glucose-6-phosphate-dehydrogenase, and 6-phosphogluconate-dehydrogenase by insulin, but not by T3

    DEFF Research Database (Denmark)

    Matzen, L E; Kristensen, S R; Kvetny, J

    1991-01-01

    The specific nuclear binding of triiodothyronine (T3) (NBT3) and the activity of malic enzyme (ME), glucose-6-phosphate-dehydrogenase (G6PD), and 6-phosphogluconate-dehydrogenase (6PGD) were studied in the human fibroblast cell (MRC-5). The overall apparent binding affinity (Ka) was 2.7 x 10(9) L...

  8. The management of uterine leiomyomas.

    Science.gov (United States)

    Vilos, George A; Allaire, Catherine; Laberge, Philippe-Yves; Leyland, Nicholas

    2015-02-01

    The aim of this guideline is to provide clinicians with an understanding of the pathophysiology, prevalence, and clinical significance of myomata and the best evidence available on treatment modalities. The areas of clinical practice considered in formulating this guideline were assessment, medical treatments, conservative treatments of myolysis, selective uterine artery occlusion, and surgical alternatives including myomectomy and hysterectomy. The risk-to-benefit ratio must be examined individually by the woman and her health care provider. Implementation of this guideline should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options, and reviewed the risks and anticipated benefits. Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2013, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to January 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The majority of fibroids are asymptomatic and require no intervention or further

  9. Fibrogenic Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion.

    Science.gov (United States)

    Ahluwalia, Neil; Grasberger, Paula E; Mugo, Brian M; Feghali-Bostwick, Carol; Pardo, Annie; Selman, Moisés; Lagares, David; Tager, Andrew M

    2016-06-01

    Pathologic accumulation of fibroblasts in pulmonary fibrosis appears to depend on their invasion through basement membranes and extracellular matrices. Fibroblasts from the fibrotic lungs of patients with idiopathic pulmonary fibrosis (IPF) have been demonstrated to acquire a phenotype characterized by increased cell-autonomous invasion. Here, we investigated whether fibroblast invasion is further stimulated by soluble mediators induced by lung injury. We found that bronchoalveolar lavage fluids from bleomycin-challenged mice or patients with IPF contain mediators that dramatically increase the matrix invasion of primary lung fibroblasts. Further characterization of this non-cell-autonomous fibroblast invasion suggested that the mediators driving this process are produced locally after lung injury and are preferentially produced by fibrogenic (e.g., bleomycin-induced) rather than nonfibrogenic (e.g., LPS-induced) lung injury. Comparison of invasion and migration induced by a series of fibroblast-active mediators indicated that these two forms of fibroblast movement are directed by distinct sets of stimuli. Finally, knockdown of multiple different membrane receptors, including platelet-derived growth factor receptor-β, lysophosphatidic acid 1, epidermal growth factor receptor, and fibroblast growth factor receptor 2, mitigated the non-cell-autonomous fibroblast invasion induced by bronchoalveolar lavage from bleomycin-injured mice, suggesting that multiple different mediators drive fibroblast invasion in pulmonary fibrosis. The magnitude of this mediator-driven fibroblast invasion suggests that its inhibition could be a novel therapeutic strategy for pulmonary fibrosis. Further elaboration of the molecular mechanisms that drive non-cell-autonomous fibroblast invasion consequently may provide a rich set of novel drug targets for the treatment of IPF and other fibrotic lung diseases.

  10. Complete uterine prolapse without uterine mucosal eversion in a queen.

    Science.gov (United States)

    Bigliardi, E; Di Ianni, F; Parmigiani, E; Cantoni, A M; Bresciani, C

    2014-04-01

    A five-year-old female cat weighing 3 kg was presented by the owner after noticing a large pink, bilobed mass protruding through the vulva during labour. The cat was in good condition, with appropriate lactation, and the newborn kittens were nursing normally. The uterus was not reverted or invaginated at examination, and there was rupture of the mesovarium, mesometrium and uterine-vaginal connection around the cervix. Manual reduction of the prolapsed uterus was not possible because of torn ligaments. A coeliotomy was performed to remove the ovaries, and the apex of the uterine horns was passed by the vaginal route. The remaining part of the mesometrium was disconnected, and the prolapsed uterus was removed. The queen and kittens were discharged from the hospital on the second day after surgery. An unusual feature of this case is that the prolapse was complete, without eversion of any part of the uterus through a vaginal tear.

  11. Uterine torsion in term pregnancy

    Directory of Open Access Journals (Sweden)

    Sparić Radmila

    2007-01-01

    Full Text Available Introduction Uterine torsion has been defined as a rotation of more than 45 degrees of the uterus around its long axis that occurs at the junction between the cervix and the corpus. The extent of the rotation is usually 180 degrees, although cases with torsion from 60 to 720 degrees have been reported. Aetiopathogenesis of this condition is still unclear. Establishing clinical diagnosis of this condition is difficult, but very important for reducing maternal and fetal morbidity and mortality. Clinical symptoms are either absent or nonspecific, and the diagnosis is usually made at laparotomy. Case outlineA 31-year old patient was admitted to the Institute of Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, as an emergency, seven days upon the established intrauterine fetal demise in the 40th gestation week. On uterine examination, the cervical length of 1.5 cm and dilatation of 3 cm were determined, as well as a palpable soft tissue formation, not resembling placenta praevia. Ultrasound examination confirmed fetal demise and exclusion of the presence of placenta praevia. The labor was completed by caesarean section. During surgery, uterine torsion of 180 degrees to the right was diagnosed. There was a stillborn male baby, and the cause of death was intrauterine asphyxia. A fibrosing and calcified accessory lobe 9x6x2.5 cm in size was observed on placental examination, which is a possible sign of initial gemellary pregnancy. Conclusion The clinical presentation of uterine torsion is variable and clinical examination and ultrasonographic scanning may be insufficient for diagnosis. The method of choice for establishing the diagnosis is magnetic resonance imaging. Once the diagnosis of uterine torsion in pregnancy is established, emergency laparotomy is indicated. Following caesarean delivery, it is necessary to surgically remove all the anatomical causes of torsion, and rotate the uterus back to its normal position. There are some

  12. Pharmacologic control of uterine contractility. In vitro human and in vivo monkey studies.

    Science.gov (United States)

    Johnson, W L; Harbert, G M; Martin, C B

    1975-10-15

    The exact cause and mechanism of the onset of labor are unknown but the theories are many. There is considerable evidence that prostaglandins are potent stimulants of uterine activity and may play a role in the onset of labor. Prostaglandin release may be the natural mediator of uterine contractions during labor. A group of anti-inflammatory compounds (aspirin-like compounds) that inhibit prostaglandin synthesis include indomethacin and fenoprofen. Inhibition of prostaglandin production is a reasonable approach to inhibiting premature labor. An excised muscle strip technique was used as a screening procedure for pharmacologic depression of human uterine activity in vitro, testing isoxsuprine, mesuprine, Alupent, ritodrine, indomethacin, and fenoprofen. The prostaglandin antagonists indomethacin and fenoprofen exhibited marked depressant activity. These drugs were further tested in an in vivo rhesus monkey preparation measuring uterine activity, maternal blood pressure, uterine blood flow, fetal heart rate, fetal blood pressure, and blood gases. Fenoprofen is effective in reducing uterine contractility without serious maternal or fetal side effects and shows promise as a clinically effective agent for pharmacologic control of premature labor.

  13. Fibroblast growth factor 19 entry into brain

    OpenAIRE

    Hsuchou, Hung; Pan, Weihong; Kastin, Abba J.

    2013-01-01

    Background Fibroblast growth factor (FGF)-19, an endocrine FGF protein mainly produced by the ileum, stimulates metabolic activity and alleviates obesity. FGF19 modulates metabolism after either intravenous or intracerebroventricular injection, and its receptor FGFR4 is present in the hypothalamus. This led to the question whether blood-borne FGF19 crosses the blood-brain barrier (BBB) to exert its metabolic effects. Methods We determined the pharmacokinetics of FGF19 permeation from blood to...

  14. Adenocarcinoma of the uterine cervix.

    Science.gov (United States)

    Rutledge, F N; Galakatos, A E; Wharton, J T; Smith, J P

    1975-05-01

    From January 1, 1947, through December 31, 1971, 219 patients with primary adenocarcinoma of the intact uterine cervix were treated at the M.D. Anderson Hospital and Tumor Institute. Two modes of therapy were primarily used, namely, irradiationtherapy alone and irradiation therapy plus operation. The 5 year survival resultsare 83.7 per cent for patients with Stage i disease, 48.0 per cent for patients with Stage ii disease, 29.2 per cent for patients with Stage iii disease, and 0.0 per cent for patients with Stage iv disease. The group with irradiation plus operation had a better over-all survival rate. In addition, the incidence of central and pelvic recurrent disease was remarkably lower (fourfold difference). The urologic and bowel complications are discussed. This review lends support for our practice of preoperative irradiation followed by simple (constructive) hysterectomy for selected patients eith adenocarcinoma of the uterine cervix.

  15. Features of Postmenopausal Uterine Haemorrhage

    OpenAIRE

    Izetbegovic, Sebija; Stojkanovic, Goran; Ribic, Nihad; Mehmedbasic, Eldar

    2013-01-01

    ABSTRACT Introduction: Postmenopausal uterine bleeding is a „cancer until proven otherwise”. Endometrial cancer is a typical disease among postmenopause woman, because every bleeding in this age etiology associated with endometrial cancer (10-30%). The lifespan of women today has been extended and post menopause today last one third of a woman’s life. Early diagnosis of endometrial cancer has a very high cure rate. Screening for this cancer has limits in practice and is necessary given the de...

  16. Review literature on uterine carcinosarcoma

    Directory of Open Access Journals (Sweden)

    Rajendra Singh

    2014-01-01

    Full Text Available Carcinosarcoma of the uterus is a rare gynaecological neoplasm, which is also known as malignant mixed mesodermal tumor. Traditionally this tumour has been regarded as a subtype of uterine sarcoma, and its origin remains controversial. The exact nature and prognosis was not clear in the past. It is believed that uterine carcinosarcoma have a Mullerian duct origin and have a capacity to differentiate into various mesenchymal and epithelial components. Regarding the histogensis, various theories have been given; of which ′conversion theory′ was broadly accepted. Carcinosarcoma are mostly of monoclonal origin with the carcinomatous component being the driving force. This type of tumor is broadly divided into two groups, homologous and heterologous, depending on the characteristics of the stroma or mesenchymal components of endometrial tissue. It is more frequent in black women and postmenopausal women. Radiation is a possible etiological factor but the exact etiology is not known yet. However, tamoxifen may induce carcinogenesis in some patients. Its clinical feature is very similar to endometrial carcinoma i.e. postmenopausal vaginal bleeding, have a very aggressive behavior and a poor prognosis. This pelvic malignancy is treated by multimodality therapy including surgery, chemotherapy and radiotherapy. Here we are reviewing old concepts about the disease and modern understandings of the origin, classification, pathogenesis and recent advances in the treatment of the uterine carcinosarcoma.

  17. Use of an Intubating Stylet as a Guide to Complete Uterine Curettage Complicated by Uterine Perforation

    OpenAIRE

    Baum, Jonathan D.; Sherlock, Douglas J.; Atkinson, Andrew L.

    2013-01-01

    Completion of uterine curettage may be challenging following uterine perforation even under sonographic and laparoscopic monitoring. This report illustrates the use of a flexible intubating stylet as a guide to place the suction curette into the uterine cavity when sonography and laparoscopy alone are not successful. Use of a malleable instrument such as an intubating stylet as a guide should be considered an option when insertion of the suction curette into the uterine cavity is complicated ...

  18. Potential Therapeutic Targets in Uterine Sarcomas

    OpenAIRE

    2015-01-01

    Uterine sarcomas are rare tumors accounting for 3,4% of all uterine cancers. Even after radical hysterectomy, most patients relapse or present with distant metastases. The very limited clinical benefit of adjuvant cytotoxic treatments is reflected by high mortality rates, emphasizing the need for new treatment strategies. This review summarizes rising potential targets in four distinct subtypes of uterine sarcomas: leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, and undi...

  19. Role of capsaicin-sensitive nerve fibers in uterine contractility in the rat.

    Science.gov (United States)

    Klukovits, Anna; Gaspar, Robert; Santha, Peter; Jancso, Gabor; Falkay, George

    2004-01-01

    The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.

  20. Underreporting of complete uterine rupture and uterine dehiscence in women with previous cesarean section.

    Science.gov (United States)

    Fogelberg, Maria; Baranov, Anton; Herbst, Andreas; Vikhareva, Olga

    2017-09-01

    To determine the true incidence of complete uterine rupture and uterine dehiscence among women delivered by cesarean section after a previous cesarean section. Medical records of all women who delivered at University Hospital in Malmö, Sweden, during 2005-2009 (n = 21 420) were retrieved from the electronic patient record system (EPRS). After adjustment for inaccuracies, 716 women who had undergone repeat cesarean section were identified and their operation reports were reviewed. Descriptions of complete uterine rupture or uterine dehiscence in operation reports were compared with diagnoses registered in EPRS with International Classification of Diseases codes version 10 (ICD-10). Sensitivity and specificity of complete uterine rupture registration were calculated. There were 13 women with a registered diagnosis of uterine rupture. After reviewing medical records of women with repeat cesarean section, seven additional cases of complete uterine rupture, 33 cases of uterine dehiscence and 39 cases of extremely thin myometrium were identified. The incidence of complete uterine rupture and uterine dehiscence for women who delivered by repeat cesarean section was 2.8% and 10.1%, respectively. Diagnosis of complete uterine rupture was underreported in the EPRS by 35% and diagnosis of uterine dehiscence was missing in 100% of cases.

  1. Spontaneous Uterine Rupture during Pregnancy: Case Report and ...

    African Journals Online (AJOL)

    After ultrasound scan, uterine rupture was diagnosed and an emergency .... Uterine rupture in multiparity occurs usually during labour. We think that our patient may have had uterine scar from ... abdominal pains and signs of shock, at which.

  2. Maternal uterine vascular remodeling during pregnancy.

    Science.gov (United States)

    Osol, George; Mandala, Maurizio

    2009-02-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  3. [Chronic renal failure secondary to uterine prolapse].

    Science.gov (United States)

    Peces, R; Canora, J; Venegas, J L

    2005-01-01

    Acute and chronic renal failure secondary to bilateral severe hydroureteronephrosis is a rare sequela of uterine prolapse. We report a case of neglected complete uterine prolapse in a 72-year-old patient resulting in bilateral hydroureter, hydronephrosis, and chronic renal failure. In an attempt to diminish the ureteral obstruction a vaginal pessary was used to reduce the uterine prolapse. Finally, surgical repair of prolapse by means of a vaginal hysterectomy was performed. In conclusion, all patients presenting with complete uterine prolapse should be screened to exclude urinary tract obstruction. If present, obstructive uropathy should be relieved by the reduction or repair of the prolapse before irreversible renal damage occurs.

  4. Skeletal muscle metastasis from uterine leiomyosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, J.M.; Brennan, D.D.; Taylor, D.H.; Eustace, S.J. [Cappagh National Orthopaedic Hospital, Department of Radiology, Dublin (Ireland); Holloway, D.P.; O' Keane, J.C. [Cappagh National Orthopaedic Hospital, Department of Pathology, Dublin (Ireland); Hurson, B. [Cappagh National Orthopaedic Hospital, Department of Orthopaedics, Dublin (Ireland)

    2004-11-01

    A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature. (orig.)

  5. Skeletal muscle metastasis from uterine leiomyosarcoma.

    Science.gov (United States)

    O'Brien, J M; Brennan, D D; Taylor, D H; Holloway, D P; Hurson, B; O'Keane, J C; Eustace, S J

    2004-11-01

    A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature.

  6. Evaluation and management of abnormal uterine bleeding in premenopausal women.

    Science.gov (United States)

    Sweet, Mary Gayle; Schmidt-Dalton, Tarin A; Weiss, Patrice M; Madsen, Keith P

    2012-01-01

    Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal uterine bleeding generally can be divided into anovulatory and ovulatory patterns. Chronic anovulation can lead to irregular bleeding, prolonged unopposed estrogen stimulation of the endometrium, and increased risk of endometrial cancer. Causes include polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of antipsychotics or antiepileptics. Women 35 years or older with recurrent anovulation, women younger than 35 years with risk factors for endometrial cancer, and women with excessive bleeding unresponsive to medical therapy should undergo endometrial biopsy. Treatment with combination oral contraceptives or progestins may regulate menstrual cycles. Histologic findings of hyperplasia without atypia may be treated with cyclic or continuous progestin. Women who have hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia. The levonorgestrel-releasing intrauterine system is an effective treatment for menorrhagia. Oral progesterone for 21 days per month and nonsteroidal anti-inflammatory drugs are also effective. Tranexamic acid is approved by the U.S. Food and Drug Administration for the treatment of ovulatory bleeding, but is expensive. When clear structural causes are identified or medical management is ineffective, polypectomy, fibroidectomy, uterine artery embolization, and endometrial ablation may be considered. Hysterectomy is the most definitive treatment.

  7. Physiological ER Stress Mediates the Differentiation of Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Shinsuke Matsuzaki

    Full Text Available Recently, accumulating reports have suggested the importance of endoplasmic reticulum (ER stress signaling in the differentiation of several tissues and cells, including myoblasts and osteoblasts. Secretory cells are easily subjected to ER stress during maturation of their secreted proteins. Skin fibroblasts produce and release several proteins, such as collagens, matrix metalloproteinases (MMPs, the tissue inhibitors of metalloproteinases (TIMPs and glycosaminoglycans (GAGs, and the production of these proteins is increased at wound sites. Differentiation of fibroblasts into myofibroblasts is one of the key factors for wound healing and that TGF-β can induce fibroblast differentiation into myofibroblasts, which express α-smooth muscle actin. Well-differentiated myofibroblasts show increased production of collagen and TGF-β, and bring about wound healing. In this study, we examined the effects of ER stress signaling on the differentiation of fibroblasts, which is required for wound healing, using constitutively ER stress-activated primary cultured fibroblasts. The cells expressed positive α-smooth muscle actin signals without TGF-β stimulation compared with control fibroblasts. Gel-contraction assays suggested that ER stress-treated primary fibroblasts caused stronger shrinkage of collagen gels than control cells. These results suggest that ER stress signaling could accelerate the differentiation of fibroblasts to myofibroblasts at injured sites. The present findings may provide important insights for developing therapies to improve wound healing.

  8. Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

    Science.gov (United States)

    2016-03-17

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

  9. Use of an Intubating Stylet as a Guide to Complete Uterine Curettage Complicated by Uterine Perforation

    Directory of Open Access Journals (Sweden)

    Jonathan D. Baum

    2013-01-01

    Full Text Available Completion of uterine curettage may be challenging following uterine perforation even under sonographic and laparoscopic monitoring. This report illustrates the use of a flexible intubating stylet as a guide to place the suction curette into the uterine cavity when sonography and laparoscopy alone are not successful. Use of a malleable instrument such as an intubating stylet as a guide should be considered an option when insertion of the suction curette into the uterine cavity is complicated by anatomic variation and uterine perforation.

  10. Spontaneous Uterine Rupture in a Twine Pregnancy at 25-26 Weeks Gestation in a Woman with Previous History of Laparoscopy Myomectomy

    Directory of Open Access Journals (Sweden)

    N. Soofizadeh

    2009-07-01

    Full Text Available Introduction: Uterine rupture in pregnancy is rare and often catastrophic with high incidence of fetal and maternal morbidity and mortality. The most common cause of uterine rupture is separation of previous cesarean hysterotomy scar. Other common predisposing factors to uterine rupture are previous traumatizing operations or manipulations such as curettage, perforation, myomectomy and excessive or inappropriate uterine stimulation with oxytocin.Case Report: In this case, spontaneous rupture of uterine at 25-26 weeks gestation (twin pregnancy in a 36 year old woman has been reported(G5P2A2L1. She was hospitalized so that preeclampsia can be rule out for her. She underwent laparoscopic removal of myoma and 3 months later IVF was done for her because of secondary infertility. During hospitalization, suddenly she had mild vaginal bleeding and decreased fetal movement. Emergency sonography reported that the two fetuses died and severe oligohydramnius and myomatosis uterine with the biggest size was 90mm.Conclusion: Try of labor was done for her but she didn't respond to induction and the patient was qualified for cesarean section. During the operation, the rupture of the uterine wall was seen in the site of the previous myomectomy and the two dead fetuses were observed in the abdomen without myoma in the uterin. The myoma that was reported by the sonologist was hematoma and omentoma. Uterine wall was repaired.

  11. Impact single versus double layer uterine closure in caesarean section to uterine rupture

    Directory of Open Access Journals (Sweden)

    Budi Iman Santoso

    2016-07-01

    Full Text Available Caesarean section (CS is one of the most frequent delivery methods in the world whereas the rates of CS were varied according to developing (from 3.5 to 29.2% and developed countries (21.1%. The study aims to known the impact of single versus double layer uterine closure to uterine rupture in the history of cesarean section (CS. In this case report, the clinical question is single versus double-layer uterine closure on the previous CS, gives better outcome to reduce the risk of uterine rupture. To answer this question, we search the evidence from Pub Med and Cochrane database with the keywords: and ldquo;cesarean section" and "uterine rupture" and and ldquo;uterine closure and rdquo;. The inclusion criteria are written in English and focused comparing single and double layer uterine closure to uterine rupture in the previous CS. From the searching literature, we found 3 systematic reviews and 23 articles which were relevant to the topic. After screening the abstract and language, we got 2 systematic reviews and 4 articles. At the end, only 4 articles consisting of 1 systematic review and 3 articles were included to be appraised. Based on evidences, single layer uterine closure did not increase the risk of uterine rupture. Apart from that, shorter operative times and lower estimated blood loss became the superiority of single-layer uterine closure. [Int J Reprod Contracept Obstet Gynecol 2016; 5(7.000: 2074-2078

  12. Dupuytren's Contracture: Fibroblast Contraction?

    Science.gov (United States)

    Gabbiani, Giulio; Majno, Guido

    1972-01-01

    In 6 cases of Dupuytren's disease and 1 of Ledderhose's disease, the nodules of the palmar and plantar aponeurosis were examined by light and electron microscopy. The cells composing these nodules, presumably fibroblasts, showed three significant ultrastructural features: (1) a fibrillar system similar to that of smooth muscle cells; (2) nuclear deformations such as are found in contracted cells, the severest being recognizable by light microscopy (cross-banded nuclei); (3) cell-to-cell and cell-to-stroma attachments. Based on these data and on recent information about the biology of the fibroblasts, it is suggested that these cells are fibroblasts that have modulated into contractile cells (myofibroblasts), and that their contraction plays a role in the pathogenesis of the contracture observed clinically. ImagesFig 10Fig 5Fig 11Fig 6 and 7Fig 8Fig 1Fig 2Fig 9Fig 3Fig 4 PMID:5009249

  13. Uterine prolapse in 2 dromedary camels.

    OpenAIRE

    Gutierrez, C.; Corbera, J.A.; Morales, I.; Morales, M; Navarro, R.

    2001-01-01

    Two cases of uterine prolapse in dromedary camels in a herd with concomitant cases of white muscle disease are described. Serum selenium and glutathione peroxidase in whole blood were investigated in both patients and showed statistical difference compared with a control group. Results suggest that selenium deficiency could promote uterine prolapse in dromedary camels.

  14. Polyarteritis nodosa with uterine involvement

    Directory of Open Access Journals (Sweden)

    Chihiro Hirai

    2012-12-01

    Full Text Available Polyarteritis nodosa (PAN is characterized by multisystem necrotizing vasculitis, primarily affecting small-to-medium-sized muscular arteries, and it is typically found in middle-aged men. PAN is rarely found in the female genital tract (including the uterus, and imaging of the uterus with PAN has not previously been reported. Reported is a case of a 78-year-old patient with uterus enlargement who was diagnosed with PAN through clinical findings and images. Computed tomography and magnetic resonance imaging findings of a uterus affected by PAN are presented and reviewed, and potential characteristic findings of the uterine with PAN are discussed.

  15. Leiomyosarcoma: a rare complication of uterine fibroid

    Directory of Open Access Journals (Sweden)

    Shazia Parveen

    2014-04-01

    Full Text Available Uterine sarcomas are rare tumours of mesodermal origin. Malignant change occurring in uterine fibroid is termed as leiomyosarcoma. They constitute around 2-6 % uterine malignancies and 25-36% of uterine sarcomas1. The tumour is common in women between the age group 40-50 years. It has an aggressive course and usually metastasis goes to the lungs. The prognosis for women with uterine sarcoma primarily depends on the extent of disease at the time of diagnosis and mitotic index3. Women with tumor size >5 cm in maximum diameter have poor prognosis. These tumours should be diagnosed and managed with no delay and must be followed vigilantly as the rate of recurrence and metastasis is very high. [Int J Reprod Contracept Obstet Gynecol 2014; 3(2.000: 486-487

  16. Uterine metrology devices for IUD selection.

    Science.gov (United States)

    1981-11-01

    Accurate measurements of the length of the uterine cavity would make it feasible to select an IUD that is compatible with a given cavity size. Considerable evidence exists to indicate that selecting an IUD on the basis of accurate longitudinal measurements of the uterine cavity improves IUD performance. There are study findings to suggest that as more data are available, specific IUDs can be prescribed for defined ranges of uterine cavity length. Metrology (uterine measuring) devices improve the ability of the clinican to measure accurately longitudinal and, in some instances, lateral dimensions of the uterine cavity. Longitudinal measurements depend on identifying the location of the internal os in order to determine the total length of the cervical canal. Lateral metrology devices also provide a measurement of uterine cavity width. Pain and discomfort associated with the use of the prototype lateral measurement instruments developed thus far is a major deterrent to their wide-scale use. 2 metrology devices -- the Crochet Hook Sound and the Hasson Wing Sound -- are designed to obtain longitudinal measurements of total uterine cavity length and of the length of the cervical canel. 2 new instruments -- the Cavimeter and the Hasson Wing Sound 2 -- designed to obtain both lateral and longitudinal measurements are now available for evaluation. The Hasson Wing Sound appears to be the only uterine metrology device available for service programs that could affect continuation rates of IUD users. It can measure the length of the uterine cavity directly, thus permitting improved IUD selection of individual women or the ability to exclude women who should not be IUD users because of small uterine size. An illustration of the prescriptive approach is included in a table.

  17. Uterine caliper and depth gauge

    Science.gov (United States)

    King, Loyd L.; Wheeler, Robert G.; Fish, Thomas M.

    1977-01-01

    A uterine caliper and sound consisting of an elongated body having outwardly biased resilient caliper wings and a spring-loaded slidable cervical stop. A slide on the body is operatively connected to the wings by a monofilament and operates with respect to a first scale on the body as a width indicator. A rod extending longitudinally on the body is connected to the cervical stop and cooperates with a second scale on the body as a depth indicator. The instrument can be positioned to measure the distance from the outer cervical ostium to the fundus, as read on said second scale. The wings may be allowed to open by moving the slide, and when the wings engage the utero-tubal junctions, the width may be read on said first scale. By adjustment of the caliper wings the instrument may be retracted until the resistance of the inner ostium of the cervix is felt, enabling the length of the cervical canal to be read directly by the position of the longitudinal indicator rod with respect to said second scale. The instrument may be employed to measure the width of the uterine cavity at any position between the inner ostium of the cervix and the fundus.

  18. Prostaglandin F2 alpha-induced response of the bovine ovary, oviduct (uterine tube), and uterus.

    Science.gov (United States)

    Singh, L P; Sadiku, A; Verma, O P

    1979-12-01

    Tissue strips from the ovary, (uterine tube), and oviduct, and uterus of pregnant and nonpregnant cows were tested for their contractile response to prostaglandin F2 alpha (PGF2 alpha). When 2.1 x 10(-6)M PGF2 alpha was added to the uterine strips, tension of tissues from pregnant cows increased sharply; however, tension in tissues from nonpregnant cows only increased moderately. Similar concentrations failed to elicit any response from oviductal tissues of either group. Unlike the uterus and the oviduct, the ovaries contracted slowly and irregularly. They responded with varying degrees of stimulation; ovaries from pregnant cows with brief and mild stimulation and ovaries from nonpregnant cows with slower and relatively stronger stimulation. Results indicate that the bovine ovary contracts rhythmically and that its sensitivity to PGF2 alpha decreases during pregnancy in contrast to the bovine uterus which becomes increasingly sensitive during pregnancy.

  19. Apoptosis of wound fibroblasts induced by oxidative stress.

    Science.gov (United States)

    Takahashi, Atsushi; Aoshiba, Kazutetsu; Nagai, Atsushi

    2002-06-01

    Irreversible lung parenchymal injury is usually healed by fibrosis, which depends on the abilities of fibroblasts to proliferate, migrate into the wound, and survive. Because the lung is frequently exposed to increased oxidative stress, which is thought to mediate apoptosis, we examined whether oxidative stress induces apoptosis in fibroblasts during wound healing. We performed an in vitro scratch wound assay where cultured fibroblast monolayers were exposed to H2O2 (10-500 microM) after artificial wounding. Apoptosis was evaluated by nuclear staining with Hoechst33342 or terminal deoxynucleotidyl transferase (TdT)-mediated nucleotide nick end-labeling (TUNEL). Intracellular oxidants were assessed with the peroxide-sensitive fluorochrome carboxydichlorodihydrofluorescein (CDCF). We found that repopulating fibroblasts at the wound margin, but not quiescent fibroblasts at the intact site, selectively underwent oxidant accumulation and apoptosis in response to H2O2 exposure. Some of the apoptotic cells had incorporated bromodeoxyuridine (BrdU), an indicator of proliferating cells. These results suggest that oxidative stress selectively induces apoptosis in fibroblasts that are stimulated to proliferate and/or migrate into the wound. Fibroblast apoptosis induced by oxidative stress during wound repopulation may be relevant to intractable wound healing.

  20. Murine gamma interferon fails to inhibit Toxoplasma gondii growth in murine fibroblasts.

    Science.gov (United States)

    Schwartzman, J D; Gonias, S L; Pfefferkorn, E R

    1990-01-01

    Although treatment of human macrophages or fibroblasts with human gamma interferon results in the inhibition of intracellular Toxoplasma gondii, murine gamma interferon stimulated only murine macrophages, not murine fibroblasts, to inhibit T. gondii. This species difference may be important in understanding the control of acute and chronic toxoplasmosis. PMID:2106497

  1. Functional screen of paracrine signals in breast carcinoma fibroblasts.

    Directory of Open Access Journals (Sweden)

    Gui Su

    Full Text Available Stromal fibroblasts actively participate in normal mammary gland homeostasis and in breast carcinoma growth and progression by secreting paracrine factors; however, little is known about the identity of paracrine mediators in individual patients. The purpose of this study was to characterize paracrine signaling pathways between breast carcinoma cells and breast carcinoma-associated fibroblasts (CAF or normal mammary fibroblasts (NF, respectively. CAF and NF were isolated from breast carcinoma tissue samples and adjacent normal mammary gland tissue of 28 patients. The fibroblasts were grown in 3D collagen gel co-culture with T47D human breast carcinoma cells and T47D cell growth was measured. CAF stimulated T47D cell growth to a significantly greater degree than NF. We detected a considerable inter-individual heterogeneity of paracrine interactions but identified FGF2, HB-EGF, heparanase-1 and SDF1 as factors that were consistently responsible for the activity of carcinoma-associated fibroblasts. CAF from low-grade but not high-grade carcinomas required insulin-like growth factor 1 and transforming growth factor beta 1 to stimulate carcinoma growth. Paradoxically, blocking of membrane-type 1 matrix metalloprotease stimulated T47D cell growth in co-culture with NF. The results were largely mirrored by treating the fibroblasts with siRNA oligonucleotides prior to co-culture, implicating the fibroblasts as principal production site for the secreted mediators. In summary, we identify a paracrine signaling network with inter-individual commonalities and differences. These findings have significant implications for the design of stroma-targeted therapies.

  2. The effects of solcoseryl on the growth and multiplication of chick embryo fibroblasts cultivated "in vitro".

    Science.gov (United States)

    Brasseur, R; De Paermentier, F

    1979-01-01

    The action of Solcoseryl, a free protein extract of calf blood, was studied on chick embryo fibroblasts cultivated in vitro. Solcoseryl stimulates the permitotic DNA synthesis and increases the number of mitoses.,

  3. Diffuse uterine leiomyomatosis in a child

    Energy Technology Data Exchange (ETDEWEB)

    Pai, Deepa; Coletti, Monette C.; Ladino-Torres, Maria; Caoili, Elaine [University of Michigan Health System, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Elkins, Matthew [University of Michigan Health System, Department of Pathology, Ann Arbor, MI (United States)

    2012-01-15

    Leiomyomas are the most common benign uterine tumor; however, this entity is relatively uncommon in the pediatric population. Although leiomyomas most commonly present as solitary uterine masses, unusual patterns of growth have been described including diffuse leiomyomatosis. In this condition, the myometrium of the uterus is symmetrically expanded by innumerable confluent leiomyomas; this pattern of growth is quite uncommon and has never been reported in a pediatric patient. This case report illustrates the imaging appearance of diffuse uterine leiomyomatosis in an otherwise healthy 16-year-old girl. (orig.)

  4. Neonatal uterine prolapse - a case report.

    Science.gov (United States)

    Saha, D K; Hasan, K M; Rahman, S M; Majumder, S K; Zahid, M K; Chakraborty, A K; Bari, M S

    2014-04-01

    Uterine prolapse is commonly seen in the geriatric age group. Congenital vaginouterine prolapse is a rare condition occurring in neonates and is usually associated with spinal cord malformations in about 85% of cases. Several modalities of treatment have been described for neonatal uterine prolapse. Conservative treatment in the form of simple digital reposition, use of pessary or other self-retaining device is usually sufficient to treat this condition, which is self-limiting and regressive. Here we report our first case of neonatal uterine prolapse, managed successfully with simple digital reposition.

  5. Congenital absence of uterine cervix

    Directory of Open Access Journals (Sweden)

    Selvaraj Ravi Lakshmy

    2016-10-01

    Full Text Available Cervical agenesis or dysgenesis is an extremely rare congenital anomaly. Patients with congenital absence of the cervix present with primary amenorrhea and infertility. Though it poses a diagnostic challenge to the clinician, correct diagnosis prior to surgery is possible with the help of ultrasound. Early diagnosis offers significant advantages in patient care and effective presurgical planning. This case report reviews two cases of cervical agenesis diagnosed with the help of ultrasound and later confirmed with the help of MRI. Ultrasonography is the modality of choice to define the internal genital anatomy and helps us to classify the level of obstruction or aplasia in obstructive uterine anomalies. [Int J Reprod Contracept Obstet Gynecol 2016; 5(10.000: 3634-3636

  6. Associated factors for uterine prolapse.

    Science.gov (United States)

    Gautam, S; Adhikari, R K; Dangol, A

    2012-01-01

    Uterine prolapsed is a significant public health problem in Nepal. The study was conducted in 50 women having second and third degree of uterus prolapse who were admitted in Dhulikhel Hospital for vaginal hysterectomy. A total 200 individual were taken as a control groups who were OPD attendants of Dhulikhel hospital without any sign or had no any sign and symptom of uterus prolapse . Data were collected by structured and semi-structured questionnaires and analysis done by using z test. The occurrence of uterus prolapse had significant difference among ethnicity (p value-prolapse were parity, gravida and age at last birth and work after delivery. Therefore civil society and concerned authority should work to raise awareness on the preventive measure of uterus prolapsed.

  7. The role of calcineurin in the lung fibroblasts proliferation and collagen synthesis induced by basic fibroblast growth factor

    Institute of Scientific and Technical Information of China (English)

    陈亚红; 赵鸣武; 符民桂; 姚婉贞; 唐朝枢

    2003-01-01

    Objective To investigate the role of calcineurin (CaN) in the lung fibroblast proliferation and collagen synthesis induced by basic fibroblast growth factor (bFGF).Methods We used Western blot and immunohistochemical methods for investigating the content and distribution of calcineurin in the lung tissue. Calcineurin activity in different tissues was measured using 32P-labelled substrate. In the primary culture of lung fibroblasts, 3H-thymidine (3H-TdR) and 3H-proline incorporation methods were used to study the effect of cyclosporin A(CsA), an inhibitor of calcineurin, on the lung fibroblast DNA and collagen synthesis stimulated by bFGF. Results We found that calcineurin was expressed in lung tissue and has phosphatase activity (7.1±2.0 pmol Pi/mg pr/min). CsA(10-8-10-6mol/L) inhibited lung fibroblast,3H-TdR incorporation induced by bFGF in a dose-dependent manner, with the inhibitory rates by20%, 46% and 66%(P<0.01). CsA(10-7-10-6mol/L) inhibited 3H-proline incorporation in lung fibroblasts stimulated by bFGF, with the inhibitory rates by 21% and 37%(P<0.01). In a culture medium, CsA (10-8-10-6mol/L) inhibited 3H-proline secretion induced by bFGF in a dose-dependent manner, with the inhibitory rates by 19%,29%(P<0.05) and 56% (P<0.01). CsA (10-7mol/L) could inhibit calcineurin activity by 44% in lung fibroblasts(P<0.01). Conclusions Calcineurin is expressed in lung tissue and has phosphatase activity. It is involved in the bFGF stimulated lung fibroblast DNA and collagen synthesis.

  8. Impact single versus double layer uterine closure in caesarean section to uterine rupture

    OpenAIRE

    Budi Iman Santoso; Raymond Surya; Rima Irwinda

    2016-01-01

    Caesarean section (CS) is one of the most frequent delivery methods in the world whereas the rates of CS were varied according to developing (from 3.5 to 29.2%) and developed countries (21.1%). The study aims to known the impact of single versus double layer uterine closure to uterine rupture in the history of cesarean section (CS). In this case report, the clinical question is single versus double-layer uterine closure on the previous CS, gives better outcome to reduce the risk of uterine ru...

  9. Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47{sup phox} pathway

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Ming-Horng [Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin, Taiwan (China); Lin, Zih-Chan [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liang, Chan-Jung [Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yen, Feng-Lin [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Institute of Biomedical Sciences, Sun Yat-Sen University, 70 Lienhai Rd., Kaohsiung, Taiwan (China); Chiang, Yao-Chang [Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan (China); China Medical University, Taichung, Taiwan (China); Lee, Chiang-Wen, E-mail: cwlee@gw.cgust.edu.tw [Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, Taiwan (China); Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China)

    2014-09-01

    Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases. - Highlights: • LPS activates the Nox2/p47{sup phox}/JNK/AP-1 and induces COX2 expression in Hs68 cells. • Eupafolin inhibits LPS-induced COX-2 expression via Nox2/p47{sup phox} inhibition. • Eupafolin may be used in the treatment of skin diseases involving inflammation.

  10. [Obstructive anuria secondary to uterine prolapse].

    Science.gov (United States)

    Rodríguez Alonso, A; González Blanco, A; Cachay Ayala, M E; Bonelli Martín, C i; Porta Vila, A; Lorenzo Franco, J; Cuerpo Pérez, M A; Nieto García, J

    2002-10-01

    The prevalence of obstructive uropathy linked to uterine prolapse ranges between 4% and 80%, depending on the series, probably due to the varying degree of severity of the prolapses under consideration. Renal failure or anuria is an unusual complication. Several etiopathogenic theories regarding obstructive uropathy secondary to prolapse have been put forward: ureteral compression by the uterine vessels, severe urethral angulation, ureteral compression against levator ani muscles and the elongation and narrowing of the distal ureter. The major radiological exploration used in studying the urinary tract of these patients is intravenous urography in bipedestation. Emergency treatment for obstructive anuria resulting from a uterine prolapse consists of manually replacement of the prolapse. Surgery is considered to be the definitive ideal treatment, although in the case of surgical or anaesthetic high risk patients, inserting a permanent pessary may constitute a satisfactory solution. We present a case of obstructive anuria resulting from uterine prolapse, which was successfully treated with the insertion of a ring pessary.

  11. Ovarian function after uterine artery embolisation

    African Journals Online (AJOL)

    2009-08-05

    Aug 5, 2009 ... Uterine artery embolisation (UAE) has been firmly ... Methods. Twenty-nine patients with myomas of the uterus underwent UAE using polyvinyl alcohol (PVA) particles .... that myomectomy may also limit postoperative ovarian.

  12. CT of uterine cervical myeloma: case report.

    Science.gov (United States)

    Salomon, C G; Posniak, H V; Pyle, J M

    1992-01-01

    Myelomatous involvement of the uterine cervix is rare and, to our knowledge, has not been reported previously in the radiologic literature. This report describes the computed tomographic (CT) findings and reviews differential diagnostic considerations.

  13. Uterine rupture without previous caesarean delivery

    DEFF Research Database (Denmark)

    Thisted, Dorthe L. A.; H. Mortensen, Laust; Krebs, Lone

    2015-01-01

    .3/100,000 deliveries. Multiparity (RR 8.99 (95% CI 1.86-43.29)), induction of labour (RR 3.26 (95% CI 1.24-8.57)), epidural analgesia (RR 10.78 (95% CI 4.25-27.39)), and augmentation by oxytocin (RR 9.50 (95% CI 3.15-28.63)) were associated with uterine rupture. Induction of labour was not significantly related...... to uterine rupture when adjusted for parity, epidural analgesia and augmentation by oxytocin. CONCLUSION: Although uterine rupture is rare, its association with epidural analgesia and augmentation of labour with oxytocin in multipara should be considered. Thus, vigilance should be exercised when labour...... is obstructed and there is need for epidural analgesia and/or augmentation by oxytocin in multiparous women. Due to the rare occurrence of uterine rupture caution should be exerted when interpreting the findings of this study....

  14. Function, Activity, and Membrane Targeting of Cytosolic Phospholipase A2ζ in Mouse Lung Fibroblasts*S

    OpenAIRE

    Ghosh, Moumita; Loper, Robyn; Ghomashchi, Farideh; Tucker, Dawn E.; Bonventre, Joseph V.; Gelb, Michael H.; Leslie, Christina C.

    2007-01-01

    Group IVA cytosolic phospholipase A2 (cPLA2α) initiates eicosanoid production; however, this pathway is not completely ablated in cPLA2α−/− lung fibroblasts stimulated with A23187 or serum. cPLA2α+/+ fibroblasts preferentially released arachidonic acid, but A23187-stimulated cPLA2α−/− fibroblasts non-specifically released multiple fatty acids. Arachidonic acid release from cPLA2α−/− fibroblasts was inhibited by the cPLA2α inhibitors pyrrolidine-2 (IC50, 0.03 μM) and Wyeth-1 (IC50, 0.1 μM), im...

  15. Sonographic Findings of Uterine Endometrial Stromal Sarcoma

    OpenAIRE

    Kim, Jeong-Ah; Lee, Myung Sook; Choi, Jong-Sun

    2006-01-01

    Objective The study was performed to present the sonographic findings of uterine endometrial stromal sarcoma (ESS). Materials and Methods We conducted a retrospective review of sonographic findings of 10 cases that were diagnosed as uterine ESS. The patients' ages ranged from 25 to 51 years (mean age: 36.1 years). The reviews focused on the location, margin, size, number and echotexture of the lesions. Hysterectomy (n = 9) and myomectomy (n = 1) were performed and a pathologic diagnosis was o...

  16. Uterine Prolapse: From Antiquity to Today

    Directory of Open Access Journals (Sweden)

    Keith T. Downing

    2012-01-01

    Full Text Available Uterine prolapse is a condition that has likely affected women for all of time as it is documented in the oldest medical literature. By looking at the watershed moments in its recorded history we are able to appreciate the evolution of urogynecology and to gain perspective on the challenges faced by today's female pelvic medicine and reconstructive surgeons in their attempts to treat uterine and vaginal vault prolapse.

  17. Outcomes following unilateral uterine artery embolisation.

    Science.gov (United States)

    McLucas, B; Reed, R A; Goodwin, S; Rappaport, A; Adler, L; Perrella, R; Dalrymple, J

    2002-02-01

    Uterine artery embolisation has been described as successful only when both arteries are embolised. However, results in patients with one congenitally absent or previously ligated artery are unknown. Women suffering from symptomatic uterine myomata were treated at a university teaching hospital, a community hospital and an outpatient surgery centre. Retrospective review of patient response to embolisation was assessed by chart review and questionnaire. Uterine and dominant fibroid size response was assessed by comparing pre- and post-embolisation ultrasound examinations. This study analysed three patient groups within the general population: those who underwent unilateral embolisation because of technical failure, those who ultimately underwent bilateral embolisation after initial technical failure and those who underwent unilateral embolisation because of an absent uterine artery. 12 patients underwent unilateral embolisation, 4 of whom underwent this procedure because of an absent uterine artery. Three of these four patients had a congenitally absent uterine artery arising from the internal iliac artery and all three experienced successful outcomes. The fourth patient had a previously ligated internal iliac artery and her symptoms worsened after the procedure. Eight patients had unilateral embolisation due to technical failure. Five of these patients underwent a subsequent procedure during which the contralateral uterine artery was embolised. Four of these five patients had successful outcomes and one was lost to follow-up. Another of the eight patients suffered an arterial injury leading to technical failure, and was lost to follow-up. Of the two remaining patients with unilateral technical failure, only one had a successful outcome. This study concluded that patients who undergo unilateral embolisation for technical reasons should be offered a second embolisation procedure shortly after the initial procedure. Patients with a congenitally absent uterine artery

  18. TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiao-Qing; Zhang, Dao-Liang [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhang, Ming-Jian; Guo, Meng; Zhan, Yang-Yang; Liu, Fang [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-Feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhao, Liang, E-mail: zhaol_zg@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Wang, Quan-Xing, E-mail: wqxejd@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Liu, Xu, E-mail: liuxu_xk@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China)

    2015-08-14

    Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. - Highlights: • Compared with SR, AF showed higher TRIF expression in left atrial appendage. • TRIF siRNA reversed macrophage chemotaxis induced by AngII-treated fibroblast. • TRIF siRNA reversed chemokines expressions induced by AngII in fibroblast. • AngII-stimulated atrial fibroblast proliferation was enhanced by macrophage.

  19. Potential Therapeutic Targets in Uterine Sarcomas

    Directory of Open Access Journals (Sweden)

    Tine Cuppens

    2015-01-01

    Full Text Available Uterine sarcomas are rare tumors accounting for 3,4% of all uterine cancers. Even after radical hysterectomy, most patients relapse or present with distant metastases. The very limited clinical benefit of adjuvant cytotoxic treatments is reflected by high mortality rates, emphasizing the need for new treatment strategies. This review summarizes rising potential targets in four distinct subtypes of uterine sarcomas: leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Based on clinical reports, promising approaches for uterine leiomyosarcoma patients include inhibition of VEGF and mTOR signaling, preferably in combination with other targeted or cytotoxic compounds. Currently, the only targeted therapy approved in leiomyosarcoma patients is pazopanib, a multitargeted inhibitor blocking VEGFR, PDGFR, FGFR, and c-KIT. Additionally, preclinical evidence suggests effect of the inhibition of histone deacetylases, tyrosine kinase receptors, and the mitotic checkpoint protein aurora kinase A. In low-grade endometrial stromal sarcomas, antihormonal therapies including aromatase inhibitors and progestins have proven activity. Other potential targets are PDGFR, VEGFR, and histone deacetylases. In high-grade ESS that carry the YWHAE/FAM22A/B fusion gene, the generated 14-3-3 oncoprotein is a putative target, next to c-KIT and the Wnt pathway. The observation of heterogeneity within uterine sarcoma subtypes warrants a personalized treatment approach.

  20. Potential Therapeutic Targets in Uterine Sarcomas

    Science.gov (United States)

    Cuppens, Tine; Tuyaerts, Sandra; Amant, Frédéric

    2015-01-01

    Uterine sarcomas are rare tumors accounting for 3,4% of all uterine cancers. Even after radical hysterectomy, most patients relapse or present with distant metastases. The very limited clinical benefit of adjuvant cytotoxic treatments is reflected by high mortality rates, emphasizing the need for new treatment strategies. This review summarizes rising potential targets in four distinct subtypes of uterine sarcomas: leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Based on clinical reports, promising approaches for uterine leiomyosarcoma patients include inhibition of VEGF and mTOR signaling, preferably in combination with other targeted or cytotoxic compounds. Currently, the only targeted therapy approved in leiomyosarcoma patients is pazopanib, a multitargeted inhibitor blocking VEGFR, PDGFR, FGFR, and c-KIT. Additionally, preclinical evidence suggests effect of the inhibition of histone deacetylases, tyrosine kinase receptors, and the mitotic checkpoint protein aurora kinase A. In low-grade endometrial stromal sarcomas, antihormonal therapies including aromatase inhibitors and progestins have proven activity. Other potential targets are PDGFR, VEGFR, and histone deacetylases. In high-grade ESS that carry the YWHAE/FAM22A/B fusion gene, the generated 14-3-3 oncoprotein is a putative target, next to c-KIT and the Wnt pathway. The observation of heterogeneity within uterine sarcoma subtypes warrants a personalized treatment approach. PMID:26576131

  1. Effect of storage media on the proliferation of periodontal ligament fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Lauer, H.C.; Mueller, J.G.; Gross, J.; Horster, M.F.

    1987-07-01

    The effect of storage media, which are routinely used in replantation, upon the proliferative capacity of periodontal ligament fibroblasts, was compared with the effect of a tissue culture medium. The periodontal tissue was obtained from mandibular central incisors of White New Zealand rabbits. The experiments were performed in fibroblasts derived during second subculture. The storage media were physiologic salt solution, Ringer's solution and Rivanol; the tissue culture medium was alpha-minimum essential medium without nucleosides. The incubation period was 1 hour. (/sup 3/H)-thymidine incorporation and cell counts were taken to indicate changes in the proliferative capacity of the fibroblasts. The tissue culture experiments showed that the proliferative ability of the periodontal ligament fibroblasts was dependent upon the composition of the storage medium. Physiologic salt solution, Ringer's solution and Rivanol were unable to maintain the metabolism of the fibroblasts. alpha-MEM medium, however, was capable of stimulating proliferation of the periodontal ligament fibroblasts.

  2. Leptin and Pro-Inflammatory Stimuli Synergistically Upregulate MMP-1 and MMP-3 Secretion in Human Gingival Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Rachel C Williams

    Full Text Available Gingival fibroblast-mediated extracellular matrix remodelling is implicated in the pathogenesis of periodontitis, yet the stimuli that regulate this response are not fully understood. The immunoregulatory adipokine leptin is detectable in the gingiva, human gingival fibroblasts express functional leptin receptor mRNA and leptin is known to regulate extracellular matrix remodelling responses in cardiac fibroblasts. We therefore hypothesised that leptin would enhance matrix metalloproteinase secretion in human gingival fibroblasts.We used in vitro cell culture to investigate leptin signalling and the effect of leptin on mRNA and protein expression in human gingival fibroblasts. We confirmed human gingival fibroblasts expressed cell surface leptin receptor, found leptin increased matrix metalloproteinase-1, -3, -8 and -14 expression in human gingival fibroblasts compared to unstimulated cells, and observed that leptin stimulation activated MAPK, STAT1/3 and Akt signalling in human gingival fibroblasts. Furthermore, leptin synergised with IL-1 or the TLR2 agonist pam2CSK4 to markedly enhance matrix metalloproteinase-1 and -3 production by human gingival fibroblasts. Signalling pathway inhibition demonstrated ERK was required for leptin-stimulated matrix metalloproteinase-1 expression in human gingival fibroblasts; whilst ERK, JNK, p38 and STAT3 were required for leptin+IL-1- and leptin+pam2CSK4-induced matrix metalloproteinase-1 expression. A genome-wide expression array and gene ontology analysis confirmed genes differentially expressed in leptin+IL-1-stimulated human gingival fibroblasts (compared to unstimulated cells were enriched for extracellular matrix organisation and disassembly, and revealed that matrix metalloproteinase-8 and -12 were also synergistically upregulated by leptin+IL-1 in human gingival fibroblasts.We conclude that leptin selectively enhances the expression and secretion of certain matrix metalloproteinases in human gingival

  3. Induction of labor by acupuncture electro-stimulation.

    Science.gov (United States)

    Yip, S K; Pang, J C; Sung, M L

    1976-01-01

    Induction of labor by acupuncture electro-stimulation was carried out in 31 patients. This was successful in 21 cases. The pattern of uterine contractions induced in these patients was similar to that in normal labor. No serious fetal or maternal complications occurred. The delay between the commencement of stimulation and the onset of contractions suggests that a humoral mechanism may be involved.

  4. Arecoline and oral keratinocytes may affect the collagen metabolism of fibroblasts.

    Science.gov (United States)

    Xia, Li; Tian-You, Ling; Yi-Jun, Gao; Dong-Sheng, Tang; Wen-Hui, Li

    2009-05-01

    The characteristic of oral submucous fibrosis (OSF) is related with the disturbance of synthesis and degradation of extracellular matrix. Arecoline, the areca nut (betel nut) component of betel quid, plays a major role in pathogenesis of OSF. But the exact mechanism how arecoline influences the collagen metabolism is unclear. Oral keratinocytes and fibroblasts were cocultured and keratinocytes were pre-treated by arecoline. Fibroblasts alone, fibroblasts stimulated by arecoline, fibroblasts cocultured with keratinocytes and fibroblasts cocultured with keratinocyte pre-treated by arecoline were included as the four groups in the present study. The concentration of collagen, the content and activity of matrix metalloproteinase (MMP) and the concentration of tissue inhibitor of metalloproteinase (TIMP) were assessed. The collagen production of fibroblasts decreased when cocultured with keratinocytes; when cocultured with keratinocytes pre-treated by arecoline, fibroblasts produced more soluble collagen than non-pretreated coculture group. MMP-9 was produced only in coculture groups. There was no significant difference in the two coculture groups. The activation ratio of pro-MMP-2 in arecoline pre-treated keratinocytes-fibroblasts coculture group was significantly higher than that of non-coculture groups, but no significant difference existed in the two coculture groups. TIMP-1 produced by arecoline pre-treated keratinocytes-fibroblasts coculture group was significantly higher than those by the other three groups. TIMP-1 and the interaction of oral keratinocytes and fibroblasts play important role in pathogenesis of OSF.

  5. Influence of uterine inflammation on the estrous cycle in rats.

    Science.gov (United States)

    Kaneko, Kazuyuki; Aoki, Hajime; Furuichi, Tomohiro; Hatori, Sachiko; Tanimoto, Hanako; Kawakami, Shizuo

    2004-06-01

    To investigate how uterine inflammation affects ovarian activity in rats, endometritis was induced and changes in the length of estrous cycle and serum concentrations of estradiol-17beta (E(2)) and progesterone (P(4)) were examined. A suspension of Staphylococcus aureus (bacterial solution) or iodine solution was infused into the uterine lumen at various estrous phases. When the bacterial solution was infused at estrus, metestrus, or the first day of diestrus, the following diestrus continued for 5 to 12 days. In the case of the iodine solution, regardless of the estrous phase of the infusion, the following diestrus continued for approximately 6 days. E(2) concentration after infusion of each solution did not fluctuate largely and remained at a low concentration (around 5 pg/ml). P(4) concentration was high (35-45 ng/ml) on the day following infusion, but decreased rapidly to base line values within a few days and remained thereafter at a low level (around 5 ng/ml). It is assumed that the endometritis caused by biological or chemical stimulation raises the concentration of P(4) to depress gonadotrophic hormone secretion, and hence this high P(4) concentration might inhibit the growth of ovarian follicles.

  6. Comparison of connective tissue components in the uterine ligaments between women with and without pelvic organ prolapse.

    Science.gov (United States)

    Bildircin, D; Kokcu, A; Celik, H; Sagir, D; Kefeli, M

    2014-04-01

    Aim of the study was the comparison of the connective tissue components in the uterine ligaments between the women with and without pelvic organ prolapse. This study included 15 postmenopausal women without pelvic organ prolapse who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign pathologies (control group) and 15 postmenopausal women who underwent vaginal hysterectomy because of pelvic organ prolapse (POP group). During the operation, samples for histological examination were taken from the cardinal and sacrouterine ligaments. The contents of collagen type I, collagen type III and elastin, and number and mitotic activity of fibroblasts in uterine ligaments were histopatholocially determined. The collagen type I content for the POP group was significantly higher than that of the control group. Collagen type III content, elastin content, and number and mitotic activity of fibroblasts were not significantly different between the control and POP groups. Collagen type I was found to be increased in the uterine ligaments of the POP group. The other connective tissue components did not differ between the two groups.

  7. Uterine sarcoma Part I—Uterine leiomyosarcoma: The Topic Advisory Group systematic review

    Directory of Open Access Journals (Sweden)

    Kuo-Chang Wen

    2016-08-01

    Full Text Available Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

  8. Uterine infarction in a patient with uterine adenomyosis following biochemical pregnancy.

    Science.gov (United States)

    Lee, Jae-Yeon; Hwang, Kyu-Ri; Won, Kyu-Hee; Lee, Da-Yong; Jeon, Hye-Won; Moon, Min-Hwan

    2014-12-01

    Adenomyosis is a common gynecological disorder characterized by the presence of endometrial glands and stroma deep within the myometrium associated with myometrial hypertrophy and hyperplasia. Focal uterine infarction after IVF-ET in a patient with adenomyosis following biochemical pregnancy has not been previously reported, although it occurs after uterine artery embolization in order to control symptoms caused by fibroids or adenomyosis. We report a case of a nulliparous woman who had uterine adenomyosis presenting with fever, pelvic pain and biochemical abortion after undergoing an IVF-ET procedure and the detection of a slightly elevated serum hCG. Focal uterine infarction was suspected after a pelvic magnetic resonance imaging demonstrated preserved myometrium between the endometrial cavity and inner margin of the necrotic myometrium. This case demonstrates that focal uterine infarction should be considered in the differential diagnosis of acute abdominal pain, vaginal bleeding and infectious signs in women experiencing biochemical abortion after an IVF-ET procedure.

  9. Intra-uterine contraceptive devices.

    Science.gov (United States)

    Elias, J

    1985-05-01

    Among the advantages of IUDs are the device's high continuation rate, the lack of systemic side effects, and the absence of a need for continual motivation to practice contraception. The effectiveness of plastic IUDs is directly proportional to their surface area, but the degree of excessive bleeding experienced is inversely related to device size. Thus, devices represent a compromise between large size for effectiveness and small size for acceptability. The optimum time to fit an IUD is during the 1st hald of the menstrual cycle. Absolute contraindications to IUD use include the presence of active pelvic inflammatory disease, undiagnosed irregular bleeding, a history of ectopic pregnancy or tubal surgery, and a distorted uteine cavity. Failure rates associated with IUD use range from 2-3% in the 1st year and then decrease. Since the main mechanism of action appears to be production of a sterile inflammatory reaction in the uterine cavity, the IUD prevents intrauterine pregnancy more effectively than ectopic pregnancy. Nonetheless, there is little evidence to suggest that IUD use actually increases the incidence of ectopic pregnancy. Resumption of fertility after IUD removal is not delayed. There is not need to change inert plastic IUDs in women who remain symptom free. The copper devices should be changed every 3-4 years. A search is under way for antifertility agents that can be incorporated into the device to reduce side effects. In general, the IUD is most suitable for older, parous women.

  10. Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

    Science.gov (United States)

    Esteller-Vico, A; Liu, I K M; Vaughan, B; Steffey, E P; Brosnan, R J

    2016-01-01

    Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised.

  11. Feedback Activation of Basic Fibroblast Growth Factor Signaling via the Wnt/β-Catenin Pathway in Skin Fibroblasts.

    Science.gov (United States)

    Wang, Xu; Zhu, Yuting; Sun, Congcong; Wang, Tao; Shen, Yingjie; Cai, Wanhui; Sun, Jia; Chi, Lisha; Wang, Haijun; Song, Na; Niu, Chao; Shen, Jiayi; Cong, Weitao; Zhu, Zhongxin; Xuan, Yuanhu; Li, Xiaokun; Jin, Litai

    2017-01-01

    Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts. Enzyme-linked immunosorbent assay (ELISA) analysis also showed that Wnt pathway was activated under bFGF treatment. Furthermore, treatment of fibroblasts with lithium chloride or IWR-1, an inducer and inhibitor of the Wnt signaling pathway, respectively, promoted and inhibited cell migration. Also, levels of cytosolic glycogen synthase kinase 3 beta phosphorylated at serine(9) (pGSK3β Ser(9)) and nuclear β-catenin were increased upon exposure to bFGF. Molecular and biochemical assays indicated that phosphoinositide 3-kinase (PI3K) signaling activated the GSK3β/β-catenin/Wnt signaling pathway via activation of c-Jun N-terminal kinase (JNK), suggesting that PI3K and JNK act at the upstream of β-catenin. In contrast, knock-down of β-catenin delayed fibroblast cell migration even under bFGF stimulation. RNA sequencing analysis of β-catenin knock-down fibroblasts demonstrated that β-catenin positively regulated the transcription of bFGF and FGF21. Moreover, FGF21 treatment activated AKT and JNK, and accelerated fibroblast migration to a similar extent as bFGF does. In addition, ELISA analysis demonstrated that both of bFGF and FGF21 were auto secretion factor and be regulated by Wnt pathway stimulators. Taken together, our analyses define a feedback regulatory loop between bFGF (FGF21) and Wnt signaling acting through β-catenin in skin fibroblasts.

  12. Uterine biology in pigs and sheep

    Directory of Open Access Journals (Sweden)

    Bazer Fuller W

    2012-07-01

    Full Text Available Abstract There is a dialogue between the developing conceptus (embryo-fetus and associated placental membranes and maternal uterus which must be established during the peri-implantation period for pregnancy recognition signaling, implantation, regulation of gene expression by uterine epithelial and stromal cells, placentation and exchange of nutrients and gases. The uterus provide a microenvironment in which molecules secreted by uterine epithelia or transported into the uterine lumen represent histotroph required for growth and development of the conceptus and receptivity of the uterus to implantation. Pregnancy recognition signaling mechanisms sustain the functional lifespan of the corpora lutea (CL which produce progesterone, the hormone of pregnancy essential for uterine functions that support implantation and placentation required for a successful outcome of pregnancy. It is within the peri-implantation period that most embryonic deaths occur due to deficiencies attributed to uterine functions or failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. With proper placentation, the fetal fluids and fetal membranes each have unique functions to ensure hematotrophic and histotrophic nutrition in support of growth and development of the fetus. The endocrine status of the pregnant female and her nutritional status are critical for successful establishment and maintenance of pregnancy. This review addresses the complexity of key mechanisms that are characteristic of successful reproduction in sheep and pigs and gaps in knowledge that must be the subject of research in order to enhance fertility and reproductive health of livestock species.

  13. Laparoscopic sacral suture hysteropexy for uterine prolapse.

    Science.gov (United States)

    Krause, Hannah G; Goh, Judith T W; Sloane, Kate; Higgs, Peta; Carey, Marcus P

    2006-06-01

    This study aims to describe and review a new method of uterine conservation in pelvic reconstruction for women with uterine prolapse. This is a prospective study of women who have undergone laparoscopic sacral suture hysteropexy. Structured questions, visual analogue patient satisfaction score (VAS), and vaginal examination were undertaken. Follow-up was performed by non-surgical reviewers. From July 2001 until August 2003, a total of 81 women underwent laparoscopic sacral suture hysteropexy for uterine prolapse. At a mean of 20.3 months follow-up, 76 women (93.8%) were available for questioning and 57 (70.3%) attended for examination. Sixty-five women (87.8%) had no symptoms of pelvic floor prolapse, 54 women (94.7%) had no objective evidence of uterine prolapse, and 61 women (82.4%) were satisfied with their surgery (VAS > or = 80%). Laparoscopic sacral suture hysteropexy attaches the posterior cervix to the sacral promontory via the right uterosacral ligament. Follow-up data of laparoscopic sacral suture hysteropexy indicate it to be an effective method in the management of uterine prolapse.

  14. Chorionic gonadotropin and uterine dialogue in the primate

    Directory of Open Access Journals (Sweden)

    Strakova Zuzana

    2004-07-01

    Full Text Available Abstract Implantation is a complex spatio-temporal interaction between the growing embryo and the mother, where both players need to be highly synchronized to be able to establish an effective communication to ensure a successful pregnancy. Using our in vivo baboon model we have shown that Chorionic Gonadotropin (CG, as the major trophoblast derived signal, not only rescues the corpus luteum but also modulates the uterine environment in preparation for implantation. This response is characterized by an alteration in both the morphological and biochemical activity in the three major cell types: luminal and glandular epithelium and stromal fibroblasts. Furthermore, CG and factors from the ovary have a synergistic effect on the receptive endometrium. Novel local effects of CG which influence the immune system to permit the survival of the fetal allograft and prevent endometrial cell death are also discussed in this review. An alternate extracellular signal-regulated kinase (ERK activation pathway observed in epithelial endometrial cells and the possibility of differential expression of the CG/LH-R isoforms during gestation, open many questions regarding the mechanism of action of CG and its signal transduction pathway within the primate endometrium.

  15. Actinomyces infection associated with intra-uterine device.

    Science.gov (United States)

    Santa, M C; Buschmann, B O; Daniel, S J

    1978-05-01

    Since 1926 numerous cases of Actinomyces genital infection have been reported. An association with the IUD, metallic or polyethylene, has become evident after several severe complications in patients using this contraceptive method. The route of entry, in addition to direct spread from the bowel, may be direct extention across the anal area and perineum upward through the vagina, endometrial cavity to the fallopian tubes and ovaries. The vaginal string of the IUD is thought to break the protective barrier of the cervical mucus, permitting transit of organisms from the vagina into the uterus and from there to the tubo-ovarian complexes. Vascular spread is another possible route of infection. The uterine cavity in these patients becomes a good culture medium for these organisms. In patients wearing IUDs for 1 year, 13% presented with chronic endometritis and 65% showed recognizable endometrial change, manifested by diffuse or focal round-cell infiltration. Lower abdominal pain, heavy yellow discharge, and fever and weight loss were the symptoms most frequently presented with infection by Actinomyces. A new cytologic approach of preparing smears from freshly removed Lippes loops from symptomatic patients has been reported. Resulting samples have numerous macrophages and fibroblasts. This could prove a good method for identifying Actinomyces in the patients harboring this orgasm. The case of a 54-year-old black female having worn an IUD for 12 consecutive years is summarized.

  16. Single versus double-layer uterine closure at cesarean: impact on lower uterine segment thickness at next pregnancy.

    Science.gov (United States)

    Vachon-Marceau, Chantale; Demers, Suzanne; Bujold, Emmanuel; Roberge, Stephanie; Gauthier, Robert J; Pasquier, Jean-Charles; Girard, Mario; Chaillet, Nils; Boulvain, Michel; Jastrow, Nicole

    2017-07-01

    Uterine rupture is a potential life-threatening complication during a trial of labor after cesarean delivery. Single-layer closure of the uterus at cesarean delivery has been associated with an increased risk of uterine rupture compared with double-layer closure. Lower uterine segment thickness measurement by ultrasound has been used to evaluate the quality of the uterine scar after cesarean delivery and is associated with the risk of uterine rupture. To estimate the impact of previous uterine closure on lower uterine segment thickness. Women with a previous single low-transverse cesarean delivery were recruited at 34-38 weeks' gestation. Transabdominal and transvaginal ultrasound evaluation of the lower uterine segment thickness was performed by a sonographer blinded to clinical data. Previous operative reports were reviewed to obtain the type of previous uterine closure. Third-trimester lower uterine segment thickness at the next pregnancy was compared according to the number of layers sutured and according to the type of thread for uterine closure, using weighted mean differences and multivariate logistic regression analyses. Of 1613 women recruited, with operative reports available, 495 (31%) had a single-layer and 1118 (69%) had a double-layer closure. The mean third-trimester lower uterine segment thickness was 3.3 ± 1.3 mm and the proportion with lower uterine segment thickness cesarean delivery is associated with a thicker third-trimester lower uterine segment and a reduced risk of lower uterine segment thickness <2.0 mm in the next pregnancy. The type of thread for uterine closure has no significant impact on lower uterine segment thickness. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Dysfunctional Uterine Bleeding: Questions to Discuss with Your Doctor

    Science.gov (United States)

    ... delivered to your inbox ! When You Visit Your Doctor - Dysfunctional Uterine Bleeding Dysfunctional Uterine Bleeding Questions to Discuss with Your Doctor: Do you have regular menstrual cycles? When was ...

  18. Characteristics of estrogen-induced peroxidase in mouse uterine luminal fluid

    Energy Technology Data Exchange (ETDEWEB)

    Jellinck, P.H.; Newbold, R.R.; McLachlan, J.A. (Queen' s University, Kingston, Ontario (Canada))

    1991-04-01

    Peroxidase activity in the uterine luminal fluid of mice treated with diethylstilbestrol was measured by the guaiacol assay and also by the formation of 3H2O from (2-3H)estradiol. In the radiometric assay, the generation of 3H2O and 3H-labeled water-soluble products was dependent on H2O2 (25 to 100 microM), with higher concentrations being inhibitory. Tyrosine or 2,4-dichlorophenol strongly enhanced the reaction catalyzed either by the luminal fluid peroxidase or the enzyme in the CaCl2 extract of the uterus, but decreased the formation of 3H2O from (2-3H)estradiol by lactoperoxidase in the presence of H2O2 (80 microM). NADPH, ascorbate, and cytochrome c inhibited both luminal fluid and uterine tissue peroxidase activity to the same extent, while superoxide dismutase showed a marginal activating effect. Lactoferrin, a major protein component of uterine luminal fluid, was shown not to contribute to its peroxidative activity, and such an effect by prostaglandin synthase was also ruled out. However, it was not possible to exclude eosinophil peroxidase, brought to the uterus after estrogen stimulation, as being the source of peroxidase activity in uterine luminal fluid.

  19. Uterine vascular lesions: a rare cause of abnormal uterine bleeding, reporting of two cases

    Directory of Open Access Journals (Sweden)

    Sunita Arora

    2014-06-01

    Full Text Available Uterine vascular lesions in the form of arteriovenous malformation or pseudo aneurysm are rare but potential life-threatening source of bleeding. A high index of suspicion and accurate diagnosis of the condition in a timely manner are essential because instrumentation that is often used for other causes of uterine bleeding can lead to massive hemorrhage. We describe two cases of uterine vascular malformation, one presenting as postabortal hemorrhage and other as postpartum hemorrhage. Case one presented as postabortal hemorrhage after induced abortion following dilatation and curettage. Case two presented as delayed postpartum hemorrhage after six weeks following cesarean section. In both cases diagnosis of uterine arteriovenous malformation was made on Doppler ultrasonography which was subsequently confirmed on pelvic angiography. The embolization of affected uterine arteries was performed successfully in both cases. Uterine vascular lesion should be suspected in patient with abnormal vaginal bleeding, especially who has recent medical history of induced abortion or dilatation and curettage or cesarean section and so on. Although angiography remains the gold standard for making diagnosis, Doppler ultrasonography is also a good noninvasive technique for the same. Uterine artery embolization offers a safe and effective treatment. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 749-753

  20. Superselective uterine arterial embolization with pingyangmycin-lipiodol emulsion for management of symptomatic uterine leiomyoma

    Institute of Scientific and Technical Information of China (English)

    单鸿; 黄明声; 关守海; 姜在波; 朱康顺; 李征然

    2004-01-01

    Background Uterine arterial embolization (UAE) is a safe and effective therapy for symptomatic uterine leiomyoma. This study was to assess the effectiveness and the feasibility of pingyangmycin-lipiodol emulsion (PLE) for the management of symptomatic uterine leiomyoma.Methods One hundred consecutive patients (aged 21-53 years, with 38 in average) with symptomatic uterine leiomyoma underwent superselective UAE with PLE. Clinical symptoms of the patients (including menorrhagia, bulk-related symptoms, and postprocedure-related abdominal pain) and the changes in uterine volume and tumor size after the embolization were analyzed. The patients were followed up for 8-21 months (mean, 15 months).Results Ninety-nine patients (99%, 99/100) were interviewed in their first menses circle after embolization, showing improvements in their abnormal bleeding and bulk-related symptoms to some extent. Imagiological results during follow-up showed a mean of 48% reduction in uterine volume at 6 months and a mean of 75% reduction in tumor size at 9 months. Eighty-three percent of the patients reported complete resolution of postprocedure pain within 7 days.Conclusions PLE is effective in the management of uterine leiomyoma, having superiority in alleviating postprocedure-related pain.

  1. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

    Directory of Open Access Journals (Sweden)

    Filomena M Carvalho

    2010-01-01

    Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

  2. Giant Uterine Leiomyoma. A Case Report

    Directory of Open Access Journals (Sweden)

    Luis Noel Marrero Quiala

    2014-09-01

    Full Text Available Giant uterine fibromyoma is a benign condition which has a very low incidence. Its management poses a challenge for the surgical team due to the volume of the surgical specimen and the variations in the distribution of the intra-abdominal organs caused by the uterine growth. The case of a 29-year-old patient misdiagnosed with giant hepatomegaly at admission is presented. Her symptoms included hard abdomen and feeling of heaviness. Successful completion of the interview, physical examination and imaging studies led to the correct diagnosis of giant uterine fibromyoma. Surgical treatment was applied. A total abdominal hysterectomy was performed with satisfactory results. This case is presented to the medical community for teaching purposes and due to its rarity.

  3. Giant Uterine Leiomyoma. A Case Report

    Directory of Open Access Journals (Sweden)

    Luis Noel Marrero Quiala

    2014-09-01

    Full Text Available Giant uterine fibromyoma is a benign condition which has a very low incidence. Its management poses a challenge for the surgical team due to the volume of the surgical specimen and the variations in the distribution of the intra-abdominal organs caused by the uterine growth. The case of a 29-year-old patient misdiagnosed with giant hepatomegaly at admission is presented. Her symptoms included hard abdomen and feeling of heaviness. Successful completion of the interview, physical examination and imaging studies led to the correct diagnosis of giant uterine fibromyoma. Surgical treatment was applied. A total abdominal hysterectomy was performed with satisfactory results. This case is presented to the medical community for teaching purposes and due to its rarity.

  4. Uterine geometry and IUD-induced pain.

    Science.gov (United States)

    Toppozada, M; Ismail, A A; Bakry, M A

    1986-06-01

    Sixty women using IUDs were included in two equal groups in the present study. Group I consisted of women presenting with pelvic pain for which they requested removal of the IUD, while the comparison group (group II) requested removal of the IUD for non-medical reasons. After extraction of the IUD, the Wing Sound II device was used to measure uterine cavity length and fundal transverse diameter. The uterine cavity measurements in both groups were not significantly different. When the ratios of IUD dimensions to uterine cavity measurements were compared, it was also found that there were no significant differences between groups. Factors other than discrepancies in size probably contribute to the pathogenesis of IUD-induced pain.

  5. [Ultrasonic diagnosis of congenital uterine abnormalities].

    Science.gov (United States)

    Funk, A; Fendel, H

    1988-01-01

    1-2% of women has abnormal uterine development due to nonunification of the Müllerian ducts in the embryonal period. At the RWTH Aachen, in the department of gynaecology and obstetrics, between January and June 1987, we had searched systematically for maldevelopment of the uterus in 2299 echosonografies. In 13 cases we found maldevelopment of internal genital; 5 of these cases were diagnosed by an echosonografic routine-examination. The echografic criteria of the different grades of uterine malformations have been determined, systematized and discussed in relation to the symptoms. The most frequent malformations as uterus subseptus, uterus septus, uterus bicornis and uterus duplex are subject of a detailed discussion. This work demonstrates that echosonografic is a very efficient instrument to diagnose uterine malformations and gives us a very exact anatomic interpretation of malformations.

  6. Case Report: Pregnancy Associated Uterine Prolapse

    Directory of Open Access Journals (Sweden)

    Alev Ozer

    2016-07-01

    Full Text Available Uterine prolapse that appears for the first time during pregnancy is a rarely encountered clinical entity, complicating 1 in 10000 to 1 in 15000 deliveries. A 30-year-old, gravida 3, para 2 woman with a 35-week-old pregnancy who was admitted to the study center was diagnosed with stage III C uterine prolapse according to the Pelvic Organ Prolapse Quantification System. Bed rest in the Trendelenburg position and administration of saline soaks for the reduction of cervical edema were recommended for the palliative treatment of the patient. Five weeks later, a healthy male baby with a birthweight of 3500 grams was delivered by cesarean section. Appropriate management of pregnancy-associated uterine prolapse consists of conservative treatment modalities throughout pregnancy.

  7. Giant Uterine Fibromyoma. A Case Report

    Directory of Open Access Journals (Sweden)

    Tahiluma Santana Pedraza

    2013-12-01

    Full Text Available The uterus is the common site for multiple benign and malignant conditions. Giant uterine fibromyoma is a benign tumor of low incidence. Its management poses a challenge for the surgical team because of the volume of the surgical specimen and the variations in the distribution of intra-abdominal organs caused by uterine growth. A case of a 43-year-old patient with a history of bronchial asthma and hypertension who presented with enlargement of the abdomen and vaginal bleeding is reported. The patient was attended by the General Surgery Department of the María Genoveva Guerrero Ramos Comprehensive Diagnostic Center in the Libertador Municipality, Capital District, Venezuela. Total abdominal hysterectomy and complementary appendectomy were performed. The histopathological study showed a giant uterine fibromyoma. Postoperative progress was satisfactory. It was decided to present the case due to its rarity.

  8. Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids : 10-year outcomes from the randomized EMMY trial

    NARCIS (Netherlands)

    de Bruijn, Annefleur M.; Ankum, Willem M.; Reekers, Jim A.; Birnie, Erwin; van der Kooij, Sanne M.; Volkers, Nicole A.; Hehenkamp, Wouter J. K.

    2016-01-01

    BACKGROUND: Since 1995 uterine artery embolization has been described as an alternative for hysterectomy in patients with symptomatic fibroids. Many studies including several randomized controlled trials established uterine artery embolization as a valuable treatment. These randomized controlled

  9. Uterine Prolapse: From Antiquity to Today

    Science.gov (United States)

    Downing, Keith T.

    2012-01-01

    Uterine prolapse is a condition that has likely affected women for all of time as it is documented in the oldest medical literature. By looking at the watershed moments in its recorded history we are able to appreciate the evolution of urogynecology and to gain perspective on the challenges faced by today's female pelvic medicine and reconstructive surgeons in their attempts to treat uterine and vaginal vault prolapse. “He who cannot render an account to himself of at least three thousand years of time, will always grope in the darkness of inexperience” —Goethe, Translation of Panebaker PMID:22262975

  10. Is a history of cesarean section a risk factor for abnormal uterine bleeding in patients with uterine leiomyoma?

    OpenAIRE

    2016-01-01

    Objectives: To determine whether a history of cesarean section was a risk factor for abnormal uterine bleeding in patients with uterine leiomyomas, and to identify other risk factors for this symptom. Methods: We analyzed retrospectively, the medical records of patients who underwent hysterectomies due to the presence of uterine leiomyomas during a 6-year period (2009 and 2014) at Etlik Zubeyde Hanim Women’s Health Training and Research Hospital, Ankara, Turkey. Uterine leiomyoma was diagnose...

  11. Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction.

    Science.gov (United States)

    Saito, Masuyoshi; Yamazaki, Masashi; Maeda, Tatsuo; Matsumura, Hajime; Setoguchi, Yasuhiro; Tsuboi, Ryoji

    2012-04-01

    Keloid is a clinically intractable disease that causes disfigurement, itching, and pain due to abnormal proliferation of fibroblasts and production of collagen. Pirfenidone is a novel anti-fibrotic agent that inhibits the progression of fibrosis occurring in the keloid lesions of the lung and kidney. In order to examine whether pirfenidone has a therapeutic effect on keloid lesions, we prepared an in vitro wound contraction model with keloid fibroblasts. The gel contractility of a mixture of keloid fibroblasts and an acid-soluble collagen solution was examined with/without transforming growth factor (TGF)-β1 in the presence or absence of pirfenidone. Real time RT-PCR was performed to detect mRNA expression of TGFB1, CTGF, aSMA, and Col1A1 quantitatively in keloid fibroblasts incubated with/without TGF-β1 in the presence or absence of pirfenidone. The contractility of keloid fibroblast-embedded collagen gel was increased after the addition of TGF-β1. Pirfenidone suppressed gel contraction with TGF-β1 dose dependently. TGF-β1 stimulated mRNA expression of TGFB1, CTGF, aSMA, and Col1A1 in keloid fibroblasts, while pirfenidone significantly inhibited mRNA expression of CTGF and aSMA in the identical cells. These findings suggest that pirfenidone suppresses the contraction of keloid-derived fibroblasts by inhibiting the down-stream pathway of TGF-β1, thus demonstrating its therapeutic utility for the treatment of keloid lesions.

  12. Adiponectin Promotes Monocyte-to-Fibroblast Transition in Renal Fibrosis

    Science.gov (United States)

    Yang, Jun; Lin, Song-Chang; Chen, Gang; He, Liqun; Hu, Zhaoyong; Chan, Lawrence; Trial, JoAnn; Entman, Mark L.

    2013-01-01

    Bone marrow–derived fibroblasts may contribute substantially to the pathogenesis of renal fibrosis through the excessive production and deposition of extracellular matrix. However, the mechanisms underlying the accumulation and activation of these fibroblasts are not understood. Here, we used a mouse model of tubulointerstitial fibrosis to determine whether adiponectin, which is elevated in CKD and is associated with disease progression, regulates monocyte-to-fibroblast transition and fibroblast activation in injured kidneys. In wild-type mice, the expression of adiponectin and the number of bone marrow–derived fibroblasts in the kidney increased after renal obstruction. In contrast, the obstructed kidneys of adiponectin-knockout mice had fewer bone marrow–derived fibroblasts. Adiponectin deficiency also led to a reduction in the number of myofibroblasts, the expression of profibrotic chemokines and cytokines, and the number of procollagen-expressing M2 macrophages in injured kidneys. Consistent with these findings, adiponectin-deficiency reduced the expression of collagen I and fibronectin. Similar results were observed in wild-type and adiponectin-knockout mice after ischemia-reperfusion injury. In cultured bone marrow–derived monocytes, adiponectin stimulated the expression of α-smooth muscle actin (SMA) and extracellular matrix proteins and activated AMP-activated protein kinase (AMPK) in a time- and dose-dependent manner. Furthermore, specific activation of AMPK increased the expression of α-SMA and extracellular matrix proteins, while inhibition of AMPK attenuated these responses. Taken together, these findings identify adiponectin as a critical regulator of monocyte-to-fibroblast transition and renal fibrosis, suggesting that inhibition of adiponectin/AMPK signaling may represent a novel therapeutic target for fibrotic kidney disease. PMID:23833260

  13. The hallmarks of fibroblast ageing.

    Science.gov (United States)

    Tigges, Julia; Krutmann, Jean; Fritsche, Ellen; Haendeler, Judith; Schaal, Heiner; Fischer, Jens W; Kalfalah, Faiza; Reinke, Hans; Reifenberger, Guido; Stühler, Kai; Ventura, Natascia; Gundermann, Sabrina; Boukamp, Petra; Boege, Fritz

    2014-06-01

    Ageing is influenced by the intrinsic disposition delineating what is maximally possible and extrinsic factors determining how that frame is individually exploited. Intrinsic and extrinsic ageing processes act on the dermis, a post-mitotic skin compartment mainly consisting of extracellular matrix and fibroblasts. Dermal fibroblasts are long-lived cells constantly undergoing damage accumulation and (mal-)adaptation, thus constituting a powerful indicator system for human ageing. Here, we use the systematic of ubiquitous hallmarks of ageing (Lopez-Otin et al., 2013, Cell 153) to categorise the available knowledge regarding dermal fibroblast ageing. We discriminate processes inducible in culture from phenomena apparent in skin biopsies or primary cells from old donors, coming to the following conclusions: (i) Fibroblasts aged in culture exhibit most of the established, ubiquitous hallmarks of ageing. (ii) Not all of these hallmarks have been detected or investigated in fibroblasts aged in situ (in the skin). (iii) Dermal fibroblasts aged in vitro and in vivo exhibit additional features currently not considered ubiquitous hallmarks of ageing. (iv) The ageing process of dermal fibroblasts in their physiological tissue environment has only been partially elucidated, although these cells have been a preferred model of cell ageing in vitro for decades. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms.

    Science.gov (United States)

    Zhang, Shuang; Kong, Shuangbo; Wang, Bingyan; Cheng, Xiaohong; Chen, Yongjie; Wu, Weiwei; Wang, Qiang; Shi, Junchao; Zhang, Ying; Wang, Shumin; Lu, Jinhua; Lydon, John P; DeMayo, Francesco; Pear, Warren S; Han, Hua; Lin, Haiyan; Li, Lei; Wang, Hongmei; Wang, Yan-Ling; Li, Bing; Chen, Qi; Duan, Enkui; Wang, Haibin

    2014-08-01

    Coordinated uterine-embryonic axis formation and decidual remodeling are hallmarks of mammalian post-implantation embryo development. Embryonic-uterine orientation is determined at initial implantation and synchronized with decidual development. However, the molecular mechanisms controlling these events remain elusive despite its discovery a long time ago. In the present study, we found that uterine-specific deletion of Rbpj, the nuclear transducer of Notch signaling, resulted in abnormal embryonic-uterine orientation and decidual patterning at post-implantation stages, leading to substantial embryo loss. We further revealed that prior to embryo attachment, Rbpj confers on-time uterine lumen shape transformation via physically interacting with uterine estrogen receptor (ERα) in a Notch pathway-independent manner, which is essential for the initial establishment of embryo orientation in alignment with uterine axis. While at post-implantation stages, Rbpj directly regulates the expression of uterine matrix metalloproteinase in a Notch pathway-dependent manner, which is required for normal post-implantation decidual remodeling. These results demonstrate that uterine Rbpj is essential for normal embryo development via instructing the initial embryonic-uterine orientation and ensuring normal decidual patterning in a stage-specific manner. Our data also substantiate the concept that normal mammalian embryonic-uterine orientation requires proper guidance from developmentally controlled uterine signaling.

  15. A COMPARATIVE STUDY ON COPPER-PLATED UTERINE CAVITY SHAPED IUD AND NON-COPPER BEARING UTERINE CAVITY SHAPED IUD

    Institute of Scientific and Technical Information of China (English)

    ZENGQing-Gu; etal

    1989-01-01

    A comparative randomized clinical trial was carried out between two uterine cavity shaped IUDs: the copper-plated uterine cavity shaped IUD(UCDCu) and non-copper bearing uterine cavity shaped IUD(UCD). The IUDs were used by 1004 and 1005 women

  16. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    François Huaux

    Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

  17. Impact of spontaneous fibroid expulsion of uterine leiomyoma on pregnancy outcome after uterine arteries embolization

    Directory of Open Access Journals (Sweden)

    Medvediev M.V.

    2015-09-01

    Full Text Available Uterine leiomyoma (UL is common benign tumor of female genitals. Uterine artery embolization (UAE is widely used method of organ-sparing UL treatment. Safe ty of this procedure for future fertility and labor is controversial. We present a case of pregnancy in woman who previously underwent uterine artery embolization. During 12-months’ follow-up period patient periodically noted vaginal di¬scharge. No signs of UL have been found on ultrasound in 12 months of follow-up. Normal pregnancy occurred 1.5 years after UAE procedure which ended in normal labor without complications. Most authors report increased risk of pregnancy complications such as postpartum hemorrhage, preterm delivery, malpresentation after UAE. Our point of view is that a lot of pregnancy complications are possibly associated with persistence of necrotic leiomyoma tissue in uterine wall after UAE. Presented case allowed to draw preliminary conclusions that complete disappearance of UL nodule after UAE could improve pregnancy outcomes.

  18. Radiotherapy for carcinoma of the uterine cervix with short uterine cavity

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Emiko; Sugita, Tadashi; Matsumoto, Yasuo; Sasamoto, Ryuta; Sakai, Kunio [Niigata Univ. (Japan). School of Medicine; Sueyama, Hiroo; Yamanoi, Tadayoshi; Ito, Takeshi; Umetsu, Hisao

    2001-11-01

    We have reviewed 11 patients treated with radiotherapy for carcinoma of the uterine cervix with short uterine cavity less than 3 cm. They consisted of 5 patients with stump cancer and 6 with atrophic uterus. Two patients with stump cancer had local failure and died of tumor progression. The 5-year cause-specific survival was 82%. Rectal and bladder injuries occurred in 5 and 2 patients, respectively. These complications were observed frequently in the patients with atrophic uterus. (author)

  19. Ultrasonic evaluation of uterine involution in Bulgarian Murrah buffalo after administration of oxytocin.

    Science.gov (United States)

    Atanasov, Anatoli S; Dineva, Julieta D; Yotov, Stanimir A

    2012-07-01

    The aim of this study was to determine the time taken for complete uterine involution in Bulgarian Murrah buffaloes following normal parturition and oxytocin stimulated milking; and to establish the time course of the change in size of the uterine horns, the cervix and caruncles between parturition and involution by means of ultrasonography. There were 17 animals in the study aged 3-6 years and average parity of 2.17 ± 0.18. They were administered 20 IU oxytocin 15 min before each milking. Rectal palpation and transrectal ultrasonography were performed at 3 d intervals from Days 1 to 34 post partum. The involution of the non-gravid and gravid uterine horns, and the cervix was complete by Days 22 and 25 post partum when their diameters were 2.7 ± 0.4 cm, 2.8 ± 0.3 cm and 3.12 ± 0.4 cm, respectively. Caruncles underwent rapid regression until Day 10 post partum. It was not possible to determine the dimensions of the caruncles after that time. The cumulative percentage of animals whose uterus was located in the pelvic cavity increased from 24% at Day 10 post partum to 100% at Day 34 post partum. The combination of rectal palpation and transrectal ultrasonography provided a reliable method of evaluating changes in the uterus over time and determining the time of uterine involution. The present study showed that complete uterine involution, with the uterus located in the pelvic cavity, was achieved by Day 34 after parturition in all 17 Bulgarian Murrah buffaloes treated with oxytocin before milking.

  20. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  1. Uterine NK cells and macrophages in pregnancy

    NARCIS (Netherlands)

    Faas, Marijke M.; de Vos, Paul

    The presence of immune cells in the placental bed is important for both mother and child. Although various immune cells can be found in the placental bed, such as regulatory T cells and dendritic cells, uterine NK cells and macrophages are the most prominent immune cells in the placental bed in

  2. Intra-uterine insemination for unexplained subfertility

    NARCIS (Netherlands)

    Verhulst, S. M.; Cohlen, B. J.; Hughes, E.; Te Velde, E.; Heineman, M. J.

    2006-01-01

    Background Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main con

  3. Intra-uterine hematoma in pregnancy

    DEFF Research Database (Denmark)

    Glavind, K; Nøhr, S; Nielsen, P H

    1991-01-01

    In 60 patients with a live fetus and an intra-uterine hematoma (IUH) proven by ultrasonic scanning the outcome of pregnancy was spontaneous abortion in 12% and premature delivery in 10%. No correlation between the outcome of the pregnancy and the maximum size of the hematoma or the week...

  4. Uterine cavity assessment prior to IVF.

    Science.gov (United States)

    Pundir, Jyotsna; El Toukhy, Tarek

    2010-11-01

    Approximately 15% of couples are affected with subfertility, of which up to 20% remain unexplained. Uterine cavity abnormalities can be a contributing cause of subfertility and recurrent implantation failure. Uterine cavity assessment has been suggested as a routine investigation in the evaluation of subfertile women. Traditionally, hysterosalpingography has been the most commonly used technique in the evaluation of infertility. Transvaginal ultrasound scan allows visualization of the endometrial lining and cavity, and has been used as a screening test for the assessment of uterine cavity. Abnormal uterine findings on a baseline scan can be further evaluated with saline hysterosonography, which is highly sensitive and specific in identifying intrauterine abnormalities. Hysteroscopy is considered as the definitive diagnostic tool to evaluate any abnormality suspected on hysterosalpingography, transvaginal ultrasound scan or saline hysterosonography during routine investigation of infertile patients. Minimally invasive hysteroscopes have minimized the pain experienced by patients during the procedure and made it feasible to use hysteroscopy as a routine outpatient examination. Following recurrent IVF failure there is some evidence of benefit from hysteroscopy in increasing the chance of pregnancy in the subsequent IVF cycle, both in those with abnormal and normal hysteroscopic findings. Various possible mechanisms have been proposed for this beneficial effect, but more randomized controlled trials are needed before its routine use in the general subfertile population can be recommended.

  5. Uterine fibroid tumors: diagnosis and treatment.

    Science.gov (United States)

    Evans, Patricia; Brunsell, Susan

    2007-05-15

    The incidence of uterine fibroid tumors increases as women grow older, and they may occur in more than 30 percent of women 40 to 60 years of age. Risk factors include nulliparity, obesity, family history, black race, and hypertension. Many tumors are asymptomatic and may be diagnosed incidentally. Although a causal relationship has not been established, fibroid tumors are associated with menorrhagia, pelvic pain, pelvic or urinary obstructive symptoms, infertility, and pregnancy loss. Transvaginal ultrasonography, magnetic resonance imaging, sonohysterography, and hysteroscopy are available to evaluate the size and position of tumors. Ultrasonography should be used initially because it is the least invasive and most cost-effective investigation. Treatment options include hysterectomy, myomectomy, uterine artery embolization, myolysis, and medical therapy. Treatment must be individualized based on such considerations as the presence and severity of symptoms, the patient's desire for definitive treatment, the desire to preserve childbearing capacity, the importance of uterine preservation, infertility related to uterine cavity distortions, and previous pregnancy complications related to fibroid tumors.

  6. Uterine leiomyosarcoma and pyometra in a dog.

    Science.gov (United States)

    Tsioli, V G; Gouletsou, P G; Loukopoulos, P; Zavlaris, M; Galatos, A D

    2011-02-01

    A seven-year-old entire female, mixed-breed dog, weighing 19 kg, was presented with a 2-day history of abdominal distension, reduced appetite and general dullness. Abdominal palpation revealed a large mass. Radiography showed a large mass occupying the left mid-abdominal area and convoluted loops of tubular fluid opacity occupying the right mid-abdominal area. Ultrasonography revealed a large heterogeneous mass with an anechoic area and some hyperechoic foci, indicative of calcification, in the mid-abdominal area. Furthermore, hypoechoic areas were found in the middle and caudal abdominal area and were presumed to be the fluid-filled uterine horns. At laparotomy, a 10·5×14·5-cm firm mass was found in the uterine body, while the uterine horns were filled with a thick red-brownish exudate; ovariohysterectomy was subsequently performed. A diagnosis of uterine leiomyosarcoma associated with pyometra was established by histopathology and immunohistochemistry. © 2011 British Small Animal Veterinary Association.

  7. Histogenesis of lipomatous component in uterine lipoleiomyomas

    Directory of Open Access Journals (Sweden)

    Filiz BOLAT

    2007-05-01

    Full Text Available Uterine neoplasms composed of an admixture of smooth muscle and adipose tissue are rare and have been designated as lipoleiomyomas. The origin of this tumor is stil controversial and it has not been sufficiently studied. The aim of our study was to investigate the immunohistochemical phenotype of fat cells in uterine lipoleiomyomas so as to clarify their origin. Archived tissue samples of 10 uterine lipoleiomyomas were selected and analyzed immunohistochemically for vimentin, desmin, and HMB-45 expression. The patients ranged from 31 to 63 years of age (mean age 53.5±9.9. Seven tumors which affected the uterine corpus, showed intramural location; while two cases were subserosal, and one was in the cervix. All tumors were constituted by irregular bundles of smooth cells and mature large adipose cells. The amount of adipose component varied from 5 to 95% of the tumor mass. Cytological atypia and necrosis were not seen. Immunohistochemical investigations revealed obvious reactivity to vimentin and desmin in perivascular immature mesencyhmal cells and tumoral smooth muscle cells. Adipose cells in the tumors demonstrated uniform vimentin expression and inconsistent desmin immunoreactivity. All adipose cells were negative for HMB-45 antigen. However, HMB-45 antigen was weakly positive in spindle shaped tumor cells of two cases. In our study, the immunohistochemical findings suggest a complex histogenesis for these tumors, which may arise from perivascular immature mesencyhmal cells or direct transformation of smooth muscle cells into adipocytes by means of progressive intracellular storage of lipids.

  8. Intra-uterine hematoma in pregnancy

    DEFF Research Database (Denmark)

    Glavind, K; Nøhr, S; Nielsen, P H

    1991-01-01

    In 60 patients with a live fetus and an intra-uterine hematoma (IUH) proven by ultrasonic scanning the outcome of pregnancy was spontaneous abortion in 12% and premature delivery in 10%. No correlation between the outcome of the pregnancy and the maximum size of the hematoma or the week of detect...

  9. Uterine NK cells and macrophages in pregnancy

    NARCIS (Netherlands)

    Faas, Marijke M; de Vos, Paul

    2017-01-01

    The presence of immune cells in the placental bed is important for both mother and child. Although various immune cells can be found in the placental bed, such as regulatory T cells and dendritic cells, uterine NK cells and macrophages are the most prominent immune cells in the placental bed in earl

  10. Uterine cornual cauterization as a sterilization method.

    Science.gov (United States)

    Ishikawa, M; Ishikawa, F

    1981-01-01

    From January 1977 to December 1978, 33 cases of uterine cornual cauterization for sterilization were performed using an ultrasound scanner to locate the uterus immediately after an induced abortion at 6-8 weeks' gestation. Hysterosalpingography was performed 16 weeks postoperatively for each patient. In every case, the Fallopian tubes had been occluded.

  11. Intra-uterine insemination for male subfertility.

    Science.gov (United States)

    Bensdorp, A J; Cohlen, B J; Heineman, M J; Vandekerckhove, P

    2007-10-17

    Intra-uterine insemination (IUI) is one of the most frequently used fertility treatments for couples with male subfertility. Its use, especially when combined with ovarian hyperstimulation (OH) has been subject of discussion. Although the treatment itself is less invasive and expensive than others, its efficacy has not been proven. Furthermore, the adverse effects of OH such as ovarian hyperstimulation syndrome (OHSS ) and multiple pregnancy are a concern. The aim of this review was to determine whether for couples with male subfertility, IUI improves the live birth rates or ongoing pregnancy rates compared with timed intercourse (TI), with or without OH. We searched the Cochrane Menstrual and Disorders Subfertility Group Trials Special Register, the Cochrane Central Register of Controlled Trials (the Cochrane Library, 2006, issue 3), MEDLINE (1966 to May 2006), EMBASE (1980 to May 2006), SCIsearch and the reference lists of articles. We hand searched abstracts of the American Society for Reproductive Medicine, the European Society for Human Reproduction and Embryology. Authors of identified articles were contacted for unpublished data. Randomised controlled trials (RCT's) with at least one of the following comparisons were included: 1) IUI versus TI or expectant management both in natural cycles 2) IUI versus TI both in cycles with OH 3) IUI in natural cycles versus TI + OH 4) IUI + OH versus TI in natural cycles 5) IUI in natural cycles versus IUI + OH. Couples with abnormal sperm parameters only were included. Two co-reviewers independently performed quality assessment and data extraction. Where possible data were pooled, and a meta-analysis was performed. Sensitivity and subgroup analyses were carried out where possible and appropriate. Three trials of parallel design, and five trials of cross-over design with pre-cross-over data were included in the meta-analysis. Three compared IUI with TI both in stimulated cycles. The remaining four of these studies

  12. Safety and one year outcomes following vaginally assisted laparoscopic uterine sacropexy (VALUES) for advanced uterine prolapse.

    Science.gov (United States)

    Fayyad, Abdalla M; Siozos, Chrysostomos S

    2014-03-01

    To assess the safety and outcomes of vaginally assisted laparoscopic uterine sacropexy (VALUES) as a surgical treatment for stage 3 and 4 uterine prolapse. Seventy consecutive women with stage 3 and 4 uterine prolapse who underwent VALUES over 2-year period were prospectively evaluated. Women filled the Prolapse Quality of Life Questionnaire (P-QOL), and underwent examination using pelvic organ prolapse quantification system (POP-Q) pre- and post-operatively. In addition, patients filled the patient global impression of improvement questionnaire post-operatively. Mesh related complications were evaluated post-operatively. Patients were followed up at 3 and 12 months following surgery. This study reports the 12 months outcomes. Sixty-four women (91.4%) reported cure of their prolapse symptoms. On examination, 67 women (95.7%) had POP-Q stage 0 or 1 uterine support at 12 months. Six women needed further surgical intervention for prolapse (8.5%); three women developed recurrent uterine prolapse and three other women developed symptomatic recurrent anterior vaginal wall prolapse. The total vaginal length was not different between the pre- and post-operative periods. Two patients developed mesh related complications. Significant improvement was noted in prolapse symptoms and quality of life. VALUES is a safe and effective treatment for women with stage 3 and 4 uterine prolapse up to 12 months without the risk of vaginal shortening. Long-term results are needed to fully establish the value of this technique. © 2013 Wiley Periodicals, Inc.

  13. Blood lactate concentration as diagnostic predictors of uterine necrosis and its outcome in dairy cows with uterine torsion

    Science.gov (United States)

    MURAKAMI, Takashi; NAKAO, Shigeru; SATO, Yohei; NAKADA, Satoshi; SATO, Akane; MUKAI, Shuhei; KOBAYASHI, Masanori; YAMADA, Yutaka; KAWAKAMI, Eiichi

    2017-01-01

    In order to determine blood lactate concentrations (bLac) and their validity as a diagnostic marker in bovine uterine torsion, blood samples were taken from 54 Holstein cows with uterine torsion before the correction of torsion. bLac in a group of cows with and without uterine necrosis were 15.0 and 3.0 mmol/l, respectively (P5.0 and >6.5 mmol/l, respectively. These findings suggest that in dairy cows with uterine torsion, an increase in bLac is a diagnostic predictor of uterine necrosis as well as poor prognosis in dams. PMID:28163266

  14. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

    Directory of Open Access Journals (Sweden)

    Tea eLanisnik Rizner

    2012-03-01

    Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

  15. Successful management of recurrent puerperal uterine inversion

    Directory of Open Access Journals (Sweden)

    Bindu Nambisan

    2016-10-01

    Full Text Available The puerperal uterine inversion is a rare and severe complication occurring in the third stage of labour. The exact mechanisms are unclear. However, extrinsic factors such as prolonged labour, umbilical cord traction, oxytocic use etc. have been mentioned. Other intrinsic factors such as primiparity, uterine hypotonia, different placental localizations, fundal location of a myoma or short umbilical cord have also been reported. The diagnosis of uterine inversion is mainly made on the basis of clinical symptoms which include haemorrhage, shock and a strong pelvic pain. The immediate treatment of the uterine inversion is required. A case of 23 years old, second gravida with one previous spontaneous first trimester abortion, who had a full term normal vaginal delivery but while trying to deliver the placenta after confirmation of placental separation clinically, uterine inversion was diagnosed immediately and manual repositioning of uterus was done under general anaesthesia. On the 6 th post natal day, during the routine postnatal rounds, uterus was not palpable per abdomen and a local examination revealed a mass at the introitus. A diagnosis of grade 3 sub-acute inversion was made and she was taken up for exploratory laparotomy. Reinsertion was done according to the Huntington technique by placing clamps on the round ligament, near its insertion on the uterus, and applying traction upwards while the assistant exerted traction on the contra lateral way through the vagina. As persistent atonicity and diffuse oozing was noted multiple Cho sutures were put over the uterus. Patient had an uneventful postnatal period. This is a rare scenario where the same patient had an acute inversion initially followed by sub-acute inversion. [Int J Reprod Contracept Obstet Gynecol 2016; 5(10.000: 3619-3621

  16. Doppler indicates of uterine artery Doppler velocimetry by placental location

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Shik; Park, Yong Won; Cho, Jae Sung; Kwon, Hye Kyeung; Kim, Jae Wook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2001-09-15

    Our purpose was to investigate the relation between the vascular resistance of uterine artery and placental location and to establish the reference value of Doppler index in uterine artery by placental location. Placental location and flow velocity waveforms of both uterine arteries in 7,016 pregnant women after 18 weeks gestation were examined using color Doppler ultrasonography. Placental location was classified as central and lateral placental and the uterine artery with lateral placental were divided into ipsilateral uterine artery (same side of the placental) and contralateral uterine artery (opposite side of the placenta). The uterine artery with central placental was classified as the central uterine artery. Systolic-Diastolic ratio (S/D ratio) of uterine arteries by gestational weeks were calculated and compared with the placental location and perinatal outcomes. In the lateral placental group, the S/D ratio of the contralateral uterine artery was higher than the ipsilateral one (mean=2.08+0.34 vs 1.89+0.34, p=0.0001). S/D ratio of the uterine artery decreased during second trimester and the ratio after 27 weeks was a tendency to have a constant values(ipsilateral: 1.85+ 0.34, central : 1.96+ 0.40, contralateral: 2.01+0.54). S/D ratio of the uterine artery was affected by placental location. So when we evaluate Doppler spectrum of uterine artery, placental location should be considered and we established the reference value of Doppler index of uterine artery by placental location.

  17. Amelogenin is phagocytized and induces changes in integrin configuration, gene expression and proliferation of cultured normal human dermal fibroblasts

    DEFF Research Database (Denmark)

    Almqvist, Sofia; Werthén, Maria; Johansson, Anna

    2010-01-01

    or down-regulation of genes, of which most are involved in cellular growth, migration and differentiation. The effect of amelogenin was exemplified by increased proliferation over 7 days. In conclusion, the beneficial effects of amelogenin on wound healing are possibly conducted by stimulating fibroblast......Fibroblasts are central in wound healing by expressing important mediators and producing and remodelling extracellular matrix (ECM) components. This study aimed at elucidating possible mechanisms of action of the ECM protein amelogenin on normal human dermal fibroblasts (NHDF). Amelogenin at 100...... signalling, proliferation and migration via integrin interactions. It is hypothesized that amelogenin stimulates wound healing by providing connective tissue cells with a temporary extracellular matrix....

  18. Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

  19. CT differentiation of solid ovarian tumor and uterine subserosal leiomyoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Rae; Cho, Kyoung Sik [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Sohn, Chul Ho [Dongsan Medical Center, Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Ji, Eun Kyung [Bombit Hospital, Seoul (Korea, Republic of)

    1999-06-01

    On the basis of CT findings, to differentiate between solid ovarian tumor and uterine subserosal myoma. In eight surgically proven cases of solid ovarian tumor and in ten uterine subserosal myoma patients, contrast-enhanced CT images were obtained. Two genitourinary radiologists reviewed the findings with regard to degree of enhancement of the mass as compared with enhancement of uterine myometrium, thickening of round ligaments, visualization of normal ovaries, contour of the mass, and the presence of ascites in the pelvic cavity. Six of eight ovarian tumors but only two of ten uterine myomas were less enhanced than normal uterine myometrium (p<0.05). Pelvic ascites were seen in six of eight ovarian tumors, but in only one of ten uterine myomas (P<0.05). Three of 16 ovaries in ovarian tumor patients, but 12 of 20 ovaries in uterine myoma patients, were normal (p<0.05). Six of 16 round ligaments of the uterus in ovarian tumor patients, were thichened but 11 of 20 round ligaments in uterine myoma patients, were thickened (p>0.05). The contour of the mass was lobulated in two of eight ovarian tumor patients, but in five of ten uterine myoma patients (p>0.05). CT findings suggestive of solid ovarian tumor were less contrast enhancement of the mass than of normal uterine myometrium, pelvic ascites, and nonvisualization of normal ovary.

  20. Uterine sarcoma Part II—Uterine endometrial stromal sarcoma: The TAG systematic review

    Directory of Open Access Journals (Sweden)

    Huann-Cheng Horng

    2016-08-01

    Full Text Available Endometrial stromal tumors are rare uterine tumors (<1%. Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS, high-grade endometrial stromal sarcoma (HG-ESS, and uterine undifferentiated sarcoma (UUS. This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS. Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.

  1. Uterine artery embolization for cervical ectopic pregnancy

    Directory of Open Access Journals (Sweden)

    Qiao Zhou, MD

    2015-12-01

    Full Text Available A 36-year-old woman with 3 prior C-sections is diagnosed with a caesarean scar ectopic pregnancy. Despite receiving intramuscular and transvaginal methotrexate injection 2 months before presentation, the beta human chorionic gonadotropin was recorded to be 73 mIU/mL at the time of encounter. The patient complained of vaginal bleeding with a significant drop in hematocrit from 40% to 33%. Transvaginal ultrasound confirmed retroplacental hemorrhage and because of the patient's desire to retain fertility, interventional radiology was consulted to perform an uterine artery embolization. The uterine artery embolization was successful in achieving hemostasis and resulted in a decrease of betaHCG to 46 on postprocedure day 1 to <1 mIU/mL by postoperative week 3.

  2. Uterine receptivity and the plasma membrane transformation

    Institute of Scientific and Technical Information of China (English)

    Christopher R MURPHY

    2004-01-01

    This review begins with a brief commentary on the diversity of placentation mechanisms, and then goes on to examine the extensive alterations which occur in the plasma membrane of uterine epithelial cells during early pregnancy across species. Ultrastructural, biochemical and more general morphological data reveal that strikingly common phenomena occur in this plasma membrane during early pregnancy despite the diversity of placental types-from epitheliochorial to hemochorial, which ultimately form in different species. To encapsulate the concept that common morphological and molecular alterations occur across species, that they are found basolaterally as well as apically, and that moreover they are an ongoing process during much of early pregnancy, not just an event at the time attachment,brane during early pregnancy are key to uterine receptivity.

  3. Uterine intravenous leiomyomatosis with right ventricular extension.

    Science.gov (United States)

    Sogabe, Masaya; Kawahito, Koji; Aizawa, Kei; Sato, Hirotaka; Misawa, Yoshio

    2014-01-01

    Intravenous leiomyomatosis is a rare neoplastic condition characterized by the benign intravascular proliferation of smooth muscle cells originating from either the uterine venous wall or a uterine leiomyoma. In the present report, we describe the case of a 45-year-old woman without a history of gynaecological surgeries, who was referred to our institution due to repeated syncopal attacks. Computed tomography indicated the presence of an intravenous leiomyoma originating from the uterus and extending to the inferior vena cava, right atrium, and right ventricle. The patient was successfully treated by cardiotomy, which was performed under hypothermic circulatory arrest, and laparotomy in a single-stage operation. She continued to recover and did not exhibit any recurrence at the 10-month follow-up.

  4. Uterine fibroids: clinical manifestations and contemporary management.

    Science.gov (United States)

    Doherty, Leo; Mutlu, Levent; Sinclair, Donna; Taylor, Hugh

    2014-09-01

    Uterine fibroids (leiomyomata) are extremely common lesions that are associated with detrimental effects including infertility and abnormal uterine bleeding. Fibroids cause molecular changes at the level of endometrium. Abnormal regulation of growth factors and cytokines in fibroid cells may contribute to negative endometrial effects. Understanding of fibroid biology has greatly increased over the last decade. Although the current armamentarium of Food and Drug Administration-approved medical therapies is limited, there are medications approved for use in heavy menstrual bleeding that can be used for the medical management of fibroids. Emergence of the role of growth factors in pathophysiology of fibroids has led researchers to develop novel therapeutics. Despite advances in medical therapies, surgical management remains a mainstay of fibroid treatment. Destruction of fibroids by interventional radiological procedures provides other effective treatments. Further experimental studies and clinical trials are required to determine which therapies will provide the greatest benefits to patients with fibroids.

  5. [Acute urologic symptoms associated with uterine myoma].

    Science.gov (United States)

    Ferreira, E L; Alexsandro da Silva, E; Pereiro, B; Roque Devesa, A; Zungri Telo, E

    1999-01-01

    While prevalence of uterine leiomyoma is high, its presentation affecting the urinary tract is uncommon. We contribute the cases of two adult women with symptoms of nephritic colic and urinary retention. Etiology was acute obstruction of the urinary tract due to previously asymptomatic urine myomas. Management in both patients was surgery, using hysterectomy to resolve the urinary obstruction. A brief review of the literature is included.

  6. Polycomb repressive complex 1 controls uterine decidualization

    OpenAIRE

    Fenghua Bian; Fei Gao; Kartashov, Andrey V.; Jegga, Anil G; Artem Barski; Das, Sanjoy K.

    2016-01-01

    Uterine stromal cell decidualization is an essential part of the reproductive process. Decidual tissue development requires a highly regulated control of the extracellular tissue remodeling; however the mechanism of this regulation remains unknown. Through systematic expression studies, we detected that Cbx4/2, Rybp, and Ring1B [components of polycomb repressive complex 1 (PRC1)] are predominantly utilized in antimesometrial decidualization with polyploidy. Immunofluorescence analyses reveale...

  7. Uterine tumors in ataxia-telangiectasia.

    Science.gov (United States)

    Gatti, R A; Nieberg, R; Boder, E

    1989-02-01

    Roughly one-third of patients with ataxia-telangiectasia (AT) develop malignant tumors, usually of lymphoid origin. AT patients also exhibit progeric changes. We describe three patients, between the ages of 27 and 32 years, with uterine tumors: one with a frank leiomyosarcoma and chronic T-cell leukemia, one with a multilobulated leiomyoma of uncertain malignant potential, and one with an unremarkable leiomyoma. Thus, the spectrum of tumors in AT patients beyond adolescence includes nonlymphoid malignancies and precocious, benign leiomyomas.

  8. Maternal and embryonic control of uterine sphingolipid-metabolizing enzymes during murine embryo implantation.

    Science.gov (United States)

    Kaneko-Tarui, Tomoko; Zhang, Ling; Austin, Kathleen J; Henkes, Luiz E; Johnson, Joshua; Hansen, Thomas R; Pru, James K

    2007-10-01

    During early gestation in invasively implanting species, the uterine stromal compartment undergoes dramatic remodeling, defined by the differentiation of stromal fibroblast cells into decidual cells. Lipid signaling molecules from a number of pathways are well-established functional components of this decidualization reaction. Because of a correlation in the events that transpire in the uterus during early implantation with known functions of bioactive sphingolipid metabolites established from studies in other organ systems, we hypothesized that uterine sphingolipid metabolism would change during implantation. By a combination of Northern blot, Western blot, and immunohistochemical analyses, we establish that enzymes at each of the major catalytic steps in the sphingolipid cascade become transcriptionally up-regulated in the uterus during decidualization. Each of the enzymes analyzed was up-regulated from Days of Pregnancy (DOP) 4.5-7.5. When comparing embryo-induced decidualization (decidual) with mechanically induced decidualization (deciduomal), sphingomyelin phosphodiesterase 1 (Smpd1) mRNA and sphingosine kinase 1 (SPHK1) protein were shown to be dually regulated in the endometrium by both maternal and embryonic factors. As measured by the diacyl glycerol kinase assay, ceramide levels rose in parallel with Smpd1 gene expression, suggesting that elevated transcription of sphingolipid enzymes results in heightened catalytic activity of the pathway. Altogether, these findings place sphingolipids on a growing list of lipid signaling molecules that become increasingly present at the maternal-embryonic interface.

  9. Sonographic Findings of Uterine Endometrial Stromal Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Ah; Lee, Myung Sook; Choi, Jong Sun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2006-12-15

    The study was performed to present the sonographic findings of uterine endometrial stromal sarcoma (ESS). We conducted a retrospective review of sonographic findings of 10 cases that were diagnosed as uterine ESS. The patients ages ranged from 25 to 51 years (mean age: 36.1 years). The reviews focused on the location, margin, size, number and echotexture of the lesions. Hysterectomy (n = 9) and myomectomy (n = 1) were performed and a pathologic diagnosis was obtained in all cases. The masses were located in the uterine wall (n = 6), or they presented as a polypoid mass protruding into the endometrial cavity from the myometrium (n = 3) or as a central cavity mass (n = 1). The lesion margins were smooth (n = 5), ill defined (n = 2), or smooth with partially nodular extensions (n = 3). The maximal mass length was 38 mm to 160 mm with a mean mass length of 83.5 mm. There were single lesions in eight cases and multiple lesions in two cases. The lesion echotextures were hypoechoic solid (n = 3), heterogeneously intermediate echoic (n = 5), diffuse myometrial thickening with heterogeneous echogenicity (n = 1) and septated cystic (n = 1). Endometrial stromal sarcoma presents with four patterns of its sonographic appearance; a polypoid mass with nodular myometrial extension, an intramural mass with an ill defined margin and heterogeneous echogenicity, an ill defined large central cavity mass or, diffuse myometrial thickening.

  10. Dealing with uterine fibroids in reproductive medicine.

    Science.gov (United States)

    Gambadauro, P

    2012-04-01

    Women who wish to conceive are nowadays more likely to present with uterine fibroids, mainly because of the delay in childbearing in our society. The relationship between uterine fibroids and human reproduction is still controversial and counselling patients might sometimes be challenging. This paper is to assist those involved in the management of patients of reproductive age presenting with uterine fibroids. The interference of fibroids on fertility largely depends on their location. Submucous fibroids interfere with fertility and should be removed in infertile patients, regardless of the size or the presence of symptoms. Intramural fibroids distorting the cavity reduce the chances of conception, while investigations on intramural fibroids not distorting the cavity have so far given controversial results. No evidence supports the systematic removal of subserosal fibroids in asymptomatic, infertile patients. Myomectomy is still the 'gold standard' in fibroid treatment for fertility-wishing patients. In experienced hands, hysteroscopic myomectomy is minimally invasive, safe, and effective. Abdominal and laparoscopic myomectomy might be challenging, but potential risks could be reduced by new strategies and techniques.

  11. Uterine transposition: technique and a case report.

    Science.gov (United States)

    Ribeiro, Reitan; Rebolho, Juliano Camargo; Tsumanuma, Fernanda Keiko; Brandalize, Giovana Gugelmin; Trippia, Carlos Henrique; Saab, Karam Abou

    2017-08-01

    To report the first uterine transposition for fertility preservation in a patient with rectal cancer. Case report. Community hospital. A 26-year-old patient with stage cT3N1M0 rectal adenocarcinoma located 5 cm from the anal margin. Laparoscopic transposition of the uterus to the upper abdomen, outside of the scope of radiation, was performed to preserve fertility. After the end of radiotherapy, rectosigmoidectomy was performed and the uterus was repositioned into the pelvis. Uterine and ovarian function preservation. The patient had two menstrual periods and exhibited normal variation in ovarian hormones throughout the course of neoadjuvant therapy. Menstruation began 2 weeks after reimplantation into the pelvis, and the cervix exhibited a normal appearance on clinical examination after 6 weeks. Eighteen months after the surgery, the uterus was normal and there was no sign of disease. Uterine transposition might represent a valid option for fertility preservation in women who require pelvic radiotherapy and want to bear children. However, studies that assess its viability, effectiveness, and safety are required. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Heterotopic respiratory mucosa of the uterine corpus

    Directory of Open Access Journals (Sweden)

    Sarala Ravindran

    2016-03-01

    Full Text Available A 47-year-old, single, Chinese woman presented with pain on the 1st day of menses for more than 30 years. Her dysmenorrhea worsened over years and underwent a total abdominal hysterectomy and bilateral salpingooophorectomy. The myometrium showed trabeculated appearance, and there were adhesions between ovaries and fallopian tubes. A pale solid brownish mass measuring 1.5 cm and times; 1 cm and times; 0.6 cm with fibrous whitish cut surfaces was present on the lateral wall of the uterus in the lower uterine segment. Histologically, adenomyosis and left ovarian endometriosis were confirmed. The lateral uterine wall nodule showed a tubular structure lined by ciliated pseudostratified columnar epithelium. Smooth muscle bundles were found around the entire tubular structure. Lobules of salivary type glands containing both serous and mucous cells are present. The pathological diagnosis of heterotopic respiratory mucosa (HRM was made. To our knowledge, this is the first reported case of HRM of the uterine corpus. [J Interdiscipl Histopathol 2016; 4(1.000: 26-28

  13. CASE REPORT - CHRONIC UTERINE INVERSION : A RARE COMPLICATION OF LABOUR

    Directory of Open Access Journals (Sweden)

    Parinita

    2015-07-01

    Full Text Available Chronic uterine inversion is a complication of mismanaged labour. It is a life threatening complication and an obstetric emergency. Early diagnosis , prompt and aggressive management reduce the morbidity and mortality. Incomplete uterine inversion left unattended or unnoticed may lead to constriction ring formation and may require surgical intervention. We report a case of chronic uterine inversion whi ch was reduced by Haultain’s repair.

  14. Intrauterine tamponade balloon use in the treatment of uterine inversion

    OpenAIRE

    Haeri, Sina; Rais, Sheliza; Monks, Brian

    2015-01-01

    Uterine inversion is a rare but life-threatening obstetrical emergency that occurs when the fundus of the uterus prolapses through the cervix, hence turning the uterus inside out. In this case report, we present our experience using an intrauterine tamponade balloon for management of uterine inversion, and a review of the literature. The utility of an intrauterine tamponade balloon in cases of uterine inversion, especially when maternal medical conditions preclude the use of uterotonics, or r...

  15. Successful Pregnancy after Treatment with Ulipristal Acetate for Uterine Fibroids

    OpenAIRE

    Javier Monleón; Alicia Martínez-Varea; Daniela Galliano; Antonio Pellicer

    2014-01-01

    This case report presents a clinical pregnancy after ulipristal acetate (UA) to decrease uterine fibroid size. A 37-year-old patient, gravida 1, abortus 1, with uterine fibroids was treated with 5 mg of UA daily for 13 weeks starting eight months after a multiple laparotomic myomectomy. Fibroid shrinkage and restoration of the morphology of endometrial cavity were evaluated in order to allow a subsequent pregnancy. A decrease of the uterine fibroids and a normal morphology of the endometrial ...

  16. Uterine cancer in the writings of ancient Greek physicians.

    Science.gov (United States)

    Tsoucalas, Gregory; Karamanou, Marianna; Sgantzos, Markos; Deligeoroglou, Efthimios; Androutsos, George

    2015-01-01

    In this article, we present the views on uterine cancer of the ancient Greek physicians. We emphasize on uterine's cancer aetiology according to the dominant in antiquity humoural theory, on its surgical treatment suggested by Soranus of Ephesus, and in the vivid description provided by Aretaeus of Cappadocia. During that period, uterine cancer was considered as an incurable and painful malignancy and its approach was mainly palliative.

  17. Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullar, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Bitsche, Mario, E-mail: Mario.Bitsche@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Schartinger, Volker, E-mail: Volker.Schartinger@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: Herbert.Riechelmann@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

    2011-09-10

    Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the

  18. Proteoglycan synthesis in normal and Lowe syndrome fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Harper, G.S.; Hascall, V.C.; Yanagishita, M.; Gahl, W.A.

    1987-04-25

    Lowe (oculocerebrorenal) syndrome (LS) is an X-linked disorder characterized by congenital cataracts, generalized hypotonia, mental retardation, and renal Fanconi syndrome. The basic defect remains unknown, but the possibility that fibroblasts express reduced sulfation of glycosaminoglycans has been studied in several laboratories. A mechanism involving overproduction of an enzyme (nucleotide pyrophosphatase) active against adenosine 3'-phosphate, 5'-phosphosulfate (PAPS) has been postulated. Decreased synthesis of normally sulfated glycosaminoglycans was also reported. We measured the synthesis of proteoglycans and glycosaminoglycans by incorporation of (/sup 3/H)glucosamine and Na/sub 2/(/sup 35/)SO/sub 4/ into cultured fibroblasts from four LS patients and related it directly to the synthesis in six normal fibroblast cultures. We found that the rate of synthesis varied greatly among the normal cultures (cv, 30%), but not significantly between LS and the normal. The LS fibroblasts' ability to sulfate glycosaminoglycans was assayed as the amount of /sup 3/H-glycosaminoglycan eluting at low ionic strength on anion exchange chromatography, the amount of non-sulfated disaccharide present in chondroitinase digests of labeled proteoglycans, and the ratio of /sup 35/S to 3H incorporation into proteoglycans. Each parameter suggested that the LS cells were synthesizing normally sulfated glycosaminoglycans (e.g. % delta Di-0S, 21 +/- 6 in normal; 27 +/- 6 in LS). The cells' ability to sulfate glycosaminoglycans was tested under conditions of markedly stimulated glycosaminoglycan synthesis, by treating the cultures with a beta-D-xyloside.

  19. Key regulatory role of dermal fibroblasts in pigmentation as demonstrated using a reconstructed skin model: impact of photo-aging.

    Directory of Open Access Journals (Sweden)

    Christine Duval

    Full Text Available To study cutaneous pigmentation in a physiological context, we have previously developed a functional pigmented reconstructed skin model composed of a melanocyte-containing epidermis grown on a dermal equivalent comprising living fibroblasts. The present studies, using the same model, aimed to demonstrate that dermal fibroblasts influence skin pigmentation up to the macroscopic level. The proof of principle was performed with pigmented skins differing only in the fibroblast component. First, the in vitro system was reconstructed with or without fibroblasts in order to test the global influence of the presence of this cell type. We then assessed the impact of the origin of the fibroblast strain on the degree of pigmentation using fetal versus adult fibroblasts. In both experiments, impressive variation in skin pigmentation at the macroscopic level was observed and confirmed by quantitative parameters related to skin color, melanin content and melanocyte numbers. These data confirmed the responsiveness of the model and demonstrated that dermal fibroblasts do indeed impact the degree of skin pigmentation. We then hypothesized that a physiological state associated with pigmentary alterations such as photo-aging could be linked to dermal fibroblasts modifications that accumulate over time. Pigmentation of skin reconstructed using young unexposed fibroblasts (n = 3 was compared to that of tissues containing natural photo-aged fibroblasts (n = 3 which express a senescent phenotype. A stimulation of pigmentation in the presence of the natural photo-aged fibroblasts was revealed by a significant increase in the skin color (decrease in Luminance and an increase in both epidermal melanin content and melanogenic gene expression, thus confirming our hypothesis. Altogether, these data demonstrate that the level of pigmentation of the skin model is influenced by dermal fibroblasts and that natural photo-aged fibroblasts can contribute to the

  20. Iatrogenic Uterine Diverticulum in Pregnancy After Robotic-assisted Myomectomy.

    Science.gov (United States)

    DeStephano, Christopher C; Jernigan, Amelia M; Szymanski, Linda M

    2015-01-01

    Uterine diverticula are rare outpouchings of the uterus associated with abnormal uterine bleeding, pelvic pain, dysmenorrhea, and adverse obstetric events. At the time of cesarean delivery at 36 5/7 weeks' gestation during the patient's first pregnancy and 36 6/7 weeks during the second pregnancy, a fundal iatrogenic uterine diverticulum at the site of a prior robotic-assisted myomectomy was noted. The outpouching communicated with the endometrial cavity and was extremely attenuated, palpably 2 to 3 mm thick. Further research is needed to determine the incidence of iatrogenic uterine diverticulum after robotic myomectomy and whether these malformations increase the risk of adverse obstetric outcomes.

  1. [Role of oxytocin in activation of spontaneous electrical activity of uterine body and uterine tubes in non-pregnant rats].

    Science.gov (United States)

    Kazarian, K V; Unanian, N G; Meliksetian, I B; Akopian, R R; Saakian, A A

    2011-01-01

    The work studies effects of various doses of oxytocin (0.01, 0.1, 1 and 10 microg/kg) on duration of discharges of spontaneous electrical activity and frequency of spikes in various parts of uterine tubes and of uterine body of non-pregnant rats. Under these conditions, changes in these parameters for ovarian parts of the uterine tubes had similar character unlike those in cervical parts of the tubes and in the middle part of the uterine body, so the latter parts can be grouped together owing to peculiarities of their changes. The longest duration of genesis of electric discharges has been shown for the ovarian part of uterine tubes at a concentration of 10 microg/kg of oxytocin. Morphological experiments revealed that among all studies areas the ovarian parts of uterine tubes were characterized by the highest amount of atypical cells that have the maximally pronounced functional activity.

  2. Uterine restoration after repeated sloughing of fibroids or vaginal expulsion following uterine artery embolization

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hye Ri; Kim, Nack Keun; Lee, Mee Hwa [Pochon CHA University, Department of Obstetrics and Gynecology, Bundang CHA General Hospital, Sungnam-si, Kyonggi-do (Korea); Kim, Man Deuk; Kim, Hee Jin; Yoon, Sang-Wook [Pochon CHA University, Department of Diagnostic Radiology, Bundang CHA General Hospital, Sungnam-si, Kyonggi-do (Korea); Park, Won Kyu [Yeungnam University, Department of Diagnostic Radiology, Kyongson, Dyongbuk (Korea)

    2005-09-01

    The aim of our study is to present our experience with uterine restoration after repeated sloughing of uterine fibroids or transvaginal expulsion following uterine artery embolization (UAE) and to determine its safety and outcome. One hundred and twenty-four women (mean age, 40.3 years; age range, 29-52 years) with symptomatic uterine fibroids were included in this retrospective study. We performed arterial embolization with poly(vinyl alcohol) particles (250-710 {mu}m). Clinical symptoms and follow-up information for each patient were obtained through medical records. At an average of 3.5 months (range, 1-8 months) after embolization, magnetic resonance imaging examinations with T1- and T2-weighted and gadolinium-enhanced T1-weighted images were obtained for all patients. The mean follow-up duration was 120 days (90-240 days). Eight (6.5%) patients experienced uterine restoration after repeated sloughing of uterine fibroids or spontaneous transvaginal expulsion. The locations of the leiomyomas were submucosal (n=5), intramural (n=2) and transmural (n=1). The maximum diameter of the fibroids ranged from 3.5 to 18.0 cm, with a mean of 8.4 cm. The time interval from embolization to the uterine restoration was 7-150 days (mean 70.5 days). The clinical symptoms before and during vaginal sloughing or expulsion were lower abdominal pain (n=4), vaginal discharges (n=3), infection of necrotic myomas (n=2) and cramping abdominal pain (n=1). Gentle abdominal compression (n=1) and hysteroscopic assistance (n=1) were required to remove the whole fibroid. No other clinical sequelae, either early or delayed, were documented. Magnetic resonance images revealed the disappearance of leiomyomas, intracavitary rupture resulting in transformation of intramural or transmural myomas into submucosal myomas and localized uterine wall defects. Although the small size of this study precludes a strict conclusion, there appear to be few serious complications directly related to vaginal

  3. Analgesic and uterine relaxant effects of isoliquiritigenin, a flavone from Glycyrrhiza glabra.

    Science.gov (United States)

    Shi, Yulu; Wu, Debin; Sun, Zhen; Yang, Jing; Chai, Hongyan; Tang, Li; Guo, Yue

    2012-09-01

    Shaoyao-gancao-tang, a Chinese medicinal formula consisting of peony and licorice has been used for the treatment of dysmenorrhea for thousands of years. The purpose of the present study was to demonstrate the analgesic and uterine relaxant effects of isoliquiritigenin (ISL), a flavonoid isolated from the roots of Glycyrrhiza glabra (a type of licorice). In vitro, isoliquiritigenin caused concentration-dependent inhibition of spontaneous contraction of isolated rat uterus and the contraction induced by various types of stimulants, such as acetylcholine (Ach, 10 mM), KCl (40 mM) and oxytocin (1 mU/mL). The uterine contractile response to cumulative concentrations of CaCl₂ was blocked by 0.1 and 1 mM of isoliquiritigenin. The isoliquiritigenin-induced relaxation was partly inhibited by the nitric oxide synthase (NOS) inhibitor Nv-nitro-L-arginine methylester (L-NAME, 100 mM) and the COX-1/COX-2 inhibitor indomethacin (10mM). In vivo, isoliquiritigenin could cause a significant reduction in the acetic acid-induced writhing response and hot-plate test at the high dose. These results indicate that isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra, not only has a spasmolytic effect on uterine contraction, which is in relation to Ca²⁺ channels, NOS and COX, but also an effective activity in reducing pain.

  4. Epithelial progesterone receptor exhibits pleiotropic roles in uterine development and function.

    Science.gov (United States)

    Franco, Heather L; Rubel, Cory A; Large, Michael J; Wetendorf, Margeaux; Fernandez-Valdivia, Rodrigo; Jeong, Jae-Wook; Spencer, Thomas E; Behringer, Richard R; Lydon, John P; Demayo, Francesco J

    2012-03-01

    The ovarian steroid progesterone, acting through the progesterone receptor (PR), coordinates endometrial epithelial-stromal cell communication, which is critical for its development and function. PR expression in these cellular compartments is under tight temporal and endocrine control. Although ex vivo studies demonstrated the importance of stromal PR expression, they failed to show a role for epithelial PR in uterine function. Here, the in vivo role of PR in the uterine epithelium is defined using floxed PR (PR(f/f)) mice crossed to Wnt7a-Cre mice. Progesterone was unable to stimulate the expression of its epithelial target genes, including Ihh, in the Wnt7a-Cre(+)PR(f/-) mice. Analysis was conducted on Ihh to determine whether PR directly regulates epithelial gene transcription. ChIP-on-chip analysis identified PR binding sites in the 5'-flanking region of Ihh. Cotransfection of the proximal Ihh promoter with PR demonstrated that PR directly regulates Ihh transcription. Female Wnt7a-Cre(+)PR(f/-) mice are infertile due to defects in embryo attachment, stromal cell decidualization, and the inability to cease estrogen-induced epithelial cell proliferation. Finally, progesterone was unable to inhibit neonatal endometrial glandular development in Wnt7a-Cre(+)PR(f/-) mice. Thus, epithelial PR is necessary for the regulation of progesterone epithelial target gene expression, as well as uterine function and development.

  5. Upregulation of the N-formyl Peptide receptors in scleroderma fibroblasts fosters the switch to myofibroblasts.

    Science.gov (United States)

    Rossi, Francesca Wanda; Napolitano, Filomena; Pesapane, Ada; Mascolo, Massimo; Staibano, Stefania; Matucci-Cerinic, Marco; Guiducci, Serena; Ragno, Pia; di Spigna, Gaetano; Postiglione, Loredana; Marone, Gianni; Montuori, Nunzia; de Paulis, Amato

    2015-06-01

    Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis. N-Formyl peptide (fMLF) receptors (FPRs) are chemotactic receptors involved in inflammation. Three FPRs have been identified: FPR1, FPR2, and FPR3. We have examined, by RT-PCR, Western blot and immunohistochemistry, FPRs expression in skin fibroblasts from 10 normal subjects and 10 SSc patients, showing increased expression in SSc fibroblasts. Several functions of FPRs occur through the interaction with a region of the urokinase-type plasminogen activator receptor (uPAR88-92), able to interact with FPRs and to mediate urokinase (uPA) or fMLF-dependent cell migration. Soluble uPAR84-95 peptide can act as a direct ligand of FPRs. Furthermore, uPA or its aminoterminal fragment (ATF) can promote the exposure of the uPAR88-92 region. The WKYMVm peptide is a FPRs pan-agonist. We investigated the functional effects of these agonists on normal and SSc fibroblasts. ATF, uPAR84-95, and WKYMVm regulated adhesion, migration, and proliferation of normal fibroblasts. Despite FPR overexpression, the response of SSc fibroblasts to the same agonists was greatly reduced, except for the proliferative response to ATF. SSc fibroblasts showed increased α-smooth muscle actin expression and improved capability to induce wound closure. Indeed, they overexpressed a cleaved uPAR form, exposing the uPAR88-92 region, and vitronectin, both involved in fibrosis and in the fibroblast-to-myofibroblast transition. FPR stimulation promoted α-smooth muscle actin expression in normal fibroblasts as well as motility, matrix deposition, αvβ5 integrin expression, and radical oxygen species generation in normal and SSc fibroblasts. This study provides evidence that FPRs may play a role in fibrosis and in the fibroblast-to-myofibroblast transition. Copyright © 2015 by The American Association of Immunologists, Inc.

  6. ABNORMAL UTERINE BLEEDING IN PERIMENOPAUSE

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    Shivaji

    2016-06-01

    Full Text Available BACKGROUND In the peri-menopausal and post-menopausal women, 70% of the gynaecological problems are due to AUB. In the United States, 11% of the hysterectomies are performed for AUB per year. During climacteric, ovarian activity declines leading to anovulation or irregular maturation of follicles. Therefore, the menstrual cycles are often anovulatory and irregular leading to AUB. Prolonged anovulatory periods with unopposed oestrogen stimulation lead to endometrial hyperplasia. This increases the risk of endometrial cancers. Over a decade the progression of endometrial hyperplasia to carcinoma is as follows: Simple hyperplasia - 1%, Complex hyperplasia - 3%, Simple hyperplasia with atypia - 8% and Complex hyperplasia with atypia 29% [Jeffcoate]. AIMS The objective of this study is to correlate the symptoms and the various menstrual patterns to the histopathological diagnosis, so that this knowledge can be applied for an early evaluation and diagnosis of the complications of AUB, and thus arrive at a timely and effective therapeutic strategies. METHODS This is a retrospective study of 314 patients of peri-menopausal age group presenting with AUB in the Department of Gynaecology at SVMCH and RC, Ariyur, Pondicherry, between 2011 and 2014. The study sample consisted of 314 samples of endometrium obtained by dilation and curettage as a day care procedure. RESULTS Menorrhagia is the predominant symptom, 128 cases [40.8%] and was associated with proliferative, secretory and hyperplastic endometrium. Metrorrhagia cases were 53 [16.9%], which predominantly showed secretory followed by proliferative histological pattern. There were 4 cases of Endometrial carcinoma [1.27%]. Simple hyperplasia with atypia were 10 cases [3.29%] and Complex hyperplasia with atypia cases were 7 [2.33%]. CONCLUSION AUB in perimenopausal period is very significant, as it accounts for about 70% of all gynaecologic outpatients. Endometrial hyperplasia is a precursor of

  7. Water-filtered near-infrared influences collagen synthesis of keloid-fibroblasts in contrast to normal foreskin fibroblasts.

    Science.gov (United States)

    Zöller, Nadja; König, Anke; Butting, Manuel; Kaufmann, Roland; Bernd, August; Valesky, Eva; Kippenberger, Stefan

    2016-10-01

    Hypertrophic scar development is associated to impaired wound healing, imbalanced fibroblast proliferation and extracellular matrix synthesis. Stigmatization, physical restrictions and high recurrence rates are only some aspects that illustrate the severe influence impaired wound healing can have on patients' life. The treatment of hypertrophic scars especially keloids is still a challenge. In recent years water-filtered near-infrared irradiation (wIRA) composed of near-infrared (NIR) and a thermal component is applied for an increasing penal of clinical purposes. It is described to beneficially influence e.g. wound healing. But discrimination between the thermal and the NIR dependent components of these effects has not been conclusively elucidated. Aim of our study was therefore to investigate the influence of the light fraction on the thermal impact of wIRA irradiation in dermal cells. We concentrated our analysis on morphological properties and collagen synthesis. Foreskin fibroblasts and the keloid fibroblast cell line KF111 were exposed to temperatures between 37°C and 46°C with or without additional irradiation with 360J/cm(2) NIR. Our results show that viability was not influenced by irradiation. Independent of the analysed fibroblast species temperature dependent occurrence of spheric cells could be observed. These morphological changes were clearly counteracted by additional light exposure. Convective heat reduced collagen type I synthesis in both cell species depending on the applied temperature. Co-treatment with NIR significantly reversed this effect in keloid fibroblast cultures treated at 46°C whereas no difference could be observed in the foreskin fibroblasts. The observed influence on collagen type I synthesis was associated to a temperature dependent TGF-β1 secretion reduction. Co-stimulation of keloid cultures with NIR at 46°C completely abolished the temperature dependent TGF-β1 secretion reduction. In foreskin fibroblast cultures co

  8. Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

    Science.gov (United States)

    Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

    2013-01-01

    The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

  9. Uterine autonomic nerve innervation plays a crucial role in regulating rat uterine mast cell functions during embryo implantation.

    Science.gov (United States)

    Yuan, Xue-Jun; Huang, Li-Bo; Qiao, Hui-Li; Deng, Ze-Pei; Fa, Jing-Jing

    2009-12-01

    To explore the potential mechanism of how uterine innervations would affect the uterine mast cell (MC) population and functions during the periimplantation. We herein first examined the consequence of uterine neurectomy on embryo implantation events. We observed that amputation of autonomic nerves innervating the uterus led to on-time implantation failure in rats. Exploiting MC culture and ELISA approaches, we then further analyzed the effect of neurectomy on cellular histamine levels and its release from uterine MCs, to elucidate the relation of the autonomic nerves and local cellular immunity in the uterine during early pregnancy. We observed that disconnection of autonomic nerve innervation significantly increased the population of uterine MCs. Most interestingly, these increased number of uterine MCs in neuroectomized rats contained a much reduced cellular level of histamine. Our subsequent challenge experiments revealed that uterine MCs in nerve amputated rats exhibited enhanced histamine releasing rate in response to substance P and antiIgE, suggesting loss of nerve innervation in the uterus not only increases the population of uterine MCs, but also facilitates the release of histamine from MCs, thus subsequently interfere with the normal implantation process. Collectively, our findings provide a new line of evidence supporting the concept that immune-neuro-endocrine network plays important role during pregnancy establishment and maintenance.

  10. Fibroblastic osteosarcoma of the mandible

    Energy Technology Data Exchange (ETDEWEB)

    Daffner, Richard H. [Department of Diagnostic Radiology, Allegheny General Hospital, Pittsburgh, PA (United States); Fox, Karl R. [Department of Laboratory Medicine, Allegheny General Hospital, Pittsburgh, PA (United States); Galey, Kent R. [Department of Surgery, Division of Oral and Maxillofacial Surgery, Allegheny General Hospital, Pittsburgh, PA (United States)

    2002-02-01

    Osteosarcoma of the mandible is a rare lesion. We report the case of a 16-year-old male who developed a fibroblastic osteosarcoma at the site of a wisdom tooth extraction. The lesion followed an aggressive course of recurrence and diffuse disseminated osteosarcomatosis. We speculate on the causal factors that resulted in this rapid course. (orig.)

  11. Patient, Physician, and Nurse Factors Associated With Entry Onto Clinical Trials and Finishing Treatment in Patients With Primary or Recurrent Uterine, Endometrial, or Cervical Cancer

    Science.gov (United States)

    2016-10-26

    Recurrent Cervical Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Uterine Corpus Sarcoma; Stage I Uterine Corpus Cancer; Stage I Uterine Sarcoma; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Uterine Sarcoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Uterine Sarcoma; Stage IV Uterine Corpus Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  12. The role of STAT1 for crosstalk between fibroblasts and colon cancer cells

    Directory of Open Access Journals (Sweden)

    Pawan eKaler

    2014-04-01

    Full Text Available Signaling between tumor cells and the associated stroma has an important impact on cancer initiation and progression. The tumor microenvironment has a paradoxical role in tumor progression and fibroblasts, a major component of the tumor stroma, have been shown to either inhibit or promote cancer development. In this study we established that normal intestinal fibroblasts activate STAT1 signaling in colon cancer cells and, in contrast to cancer- associated fibroblasts, inhibit growth of tumor cells. Treatment of 18Co fibroblasts with the proinflammatory cytokine TNF interfered with their ability to trigger STAT1 signaling in cancer cells. Accordingly, intestinal myofibroblasts isolated from patients with Ulcerative colitis (UC or Crohn’s disease (CD, which are activated and produce high levels of TNF, failed to stimulate STAT1 signaling in tumor cells, demonstrating that activated myofibroblasts lose the ability to trigger growth-inhibitory STAT1 signaling in tumor cells. Finally, we confirmed that silencing of STAT1 in tumor cells alters the crosstalk between tumor cells and fibroblasts, suggesting STAT1 as a novel link between intestinal inflammation and colon cancer. We demonstrated that normal fibroblasts restrain the growth of carcinoma cells, at least in part, through the induction of STAT1 signaling in cancer cells. We showed that changes in the microenvironment, as they occur in inflammatory bowel disease, alter the crosstalk between carcinoma cells and fibroblasts, perturb the homeostasis of intestinal tissue and thereby contribute to tumor progression.

  13. Defective alterations in the collagen network to prostacyclin in COPD lung fibroblasts

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    Larsson-Callerfelt Anna-Karin

    2013-02-01

    Full Text Available Abstract Background Prostacyclin analogs are potent vasodilators and possess anti-inflammatory properties. However, the effect of prostacyclin on extracellular matrix (ECM in COPD is not well known. Collagen fibrils and proteoglycans are essential ECM components in the lung and fibroblasts are key players in regulating the homeostasis of ECM proteins. The aim was to study the synthesis of prostacyclin and its effect on fibroblast activity and ECM production, and in particular collagen I and the collagen-associated proteoglycans biglycan and decorin. Methods Parenchymal lung fibroblasts were isolated from lungs from COPD patients (GOLD stage IV and from lungs and transbronchial biopsies from control subjects. The prostacyclin analog iloprost was used to study the effect of prostacyclin on ECM protein synthesis, migration, proliferation and contractile capacity of fibroblasts. Results TGF-β1 stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p  Conclusions Iloprost reduced collagen I synthesis and fibroblast contractility but did not affect the collagen-associated proteoglycans or proliferation rate in fibroblasts from COPD patients. Enhanced prostacyclin production could lead to improper collagen network fibrillogenesis and a more emphysematous lung structure in severe COPD patients.

  14. MORPHOFUNCTIONAL CHARACTERISTICS OF FIBROBLASTS (MCCOY CELL LINE CULTURED WITH MAGNESIUM PREPARATIONS

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    L. V. Didenko

    2015-01-01

    Full Text Available Aim. To study the effect of magnesium orotate, magnesium/pyridoxine combination and magnesium sulfate on fibroblast morphofunctional characteristics in cell culture of fibroblasts (McCoy line.Material and methods. The study of fibroblasts (McCoy line with the addition of magnesium-containing preparations (magnesium orotate, magnesium/pyridoxine combination, magnesium sulphate to the culture medium was performed using scanning and transmission electron microscopy.Results. When adding into the media magnesium orotate or magnesium/pyridoxine combination, significant changes in morphofunctional state of fibroblasts were noted, which were absent when adding magnesium sulfate. At that fibroblasts significantly promoted synthetic and secretory activity. This was expressed in the formation of amorphous and fibrous components in well-formed cell layers.Conclusion. Stimulation by magnesium ions of the proliferative activity of fibroblasts is shown in the morphological analysis of the effect of magnesium orotate or magnesium in combination with pyridoxine and magnesium sulfate on morphological and functional organization of fibroblasts. Revealed the predominant influence of magnesium orotate, and a less pronounced effect of magnesium in combination with pyridoxine on biosynthetic processes in the cells, including the synthesis of amorphous and fibrous components (protocollagen and elastin of the extracellular matrix founded.

  15. Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint

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    Toshio Hattori

    2015-01-01

    Full Text Available Synovial fibroblasts contribute to the inflammatory temporomandibular joint under pathogenic stimuli. Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. IL-17 is an inflammatory cytokine produced primarily by Th17 cells which plays critical role in the pathogenesis of numerous autoimmune and inflammatory diseases. Here, we investigated the roles of IL-17A in temporomandibular joint disorders (TMD using genome-wide analysis of synovial fibroblasts isolated from patients with TMD. IL-17 receptors were expressed in synovial fibroblasts as assessed using real-time PCR. Microarray analysis indicated that IL-17A treatment of synovial fibroblasts upregulated the expression of IL-6 and chemokines. Real-time PCR analysis showed that the gene expression of IL-6, CXCL1, IL-8, and CCL20 was significantly higher in IL-17A-treated synovial fibroblasts compared to nontreated controls. IL-6 protein production was increased by IL-17A in a time- and a dose-dependent manner. Additionally, IL-17A simulated IL-6 protein production in synovial fibroblasts samples isolated from three patients. Furthermore, signal inhibitor experiments indicated that IL-17-mediated induction of IL-6 was transduced via activation of NFκB and phosphatidylinositol 3-kinase/Akt. These results suggest that IL-17A is associated with the inflammatory progression of TMD.

  16. Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring.

    Science.gov (United States)

    Wang, JianFei; Hori, Keijiro; Ding, Jie; Huang, Yue; Kwan, Peter; Ladak, Adil; Tredget, Edward E

    2011-05-01

    Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases activation, cytokine gene transcription and co-stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT-PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL-6, IL-8, and MCP-1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore

  17. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications

    Science.gov (United States)

    Ciarmela, Pasquapina; Islam, Md. Soriful; Reis, Fernando M.; Gray, Peter C.; Bloise, Enrrico; Petraglia, Felice; Vale, Wylie; Castellucci, Mario

    2011-01-01

    BACKGROUND Growth factors are proteins secreted by a number of cell types that are capable of modulating cellular growth, proliferation and cellular differentiation. It is well accepted that uterine cellular events such as proliferation and differentiation are regulated by sex steroids and their actions in target tissues are mediated by local production of growth factors acting through paracrine and/or autocrine mechanisms. Myometrial mass is ultimately modified in pregnancy as well as in tumour conditions such as leiomyoma and leiomyosarcoma. Leiomyomas, also known as fibroids, are benign tumours of the uterus, considered to be one of the most frequent causes of infertility in reproductive years in women. METHODS For this review, we searched the database MEDLINE and Google Scholar for articles with content related to growth factors acting on myometrium; the findings are hereby reviewed and discussed. RESULTS Different growth factors such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), heparin-binding EGF (HB-EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and TGF-β perform actions in myometrium and in leiomyomas. In addition to these growth factors, activin and myostatin have been recently identified in myometrium and leiomyoma. CONCLUSIONS Growth factors play an important role in the mechanisms involved in myometrial patho-physiology. PMID:21788281

  18. Cellular signaling by fibroblast growth factor receptors.

    Science.gov (United States)

    Eswarakumar, V P; Lax, I; Schlessinger, J

    2005-04-01

    The 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosine kinases (RTKs) designated FGFR1, FGFR2, FGFR3 and FGFR4. Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and to induce the pleiotropic responses that lead to the variety of cellular responses induced by this large family of growth factors. A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development. Gain of function mutations in FGFRs were also identified in a variety of human cancers such as myeloproliferative syndromes, lymphomas, prostate and breast cancers as well as other malignant diseases. The binding of FGF and HSPG to the extracellular ligand domain of FGFR induces receptor dimerization, activation and autophosphorylation of multiple tyrosine residues in the cytoplasmic domain of the receptor molecule. A variety of signaling proteins are phosphorylated in response to FGF stimulation including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape. The docking proteins FRS2alpha and FRS2beta are major mediators of the Ras/MAPK and PI-3 kinase/Akt signaling pathways as well as negative feedback mechanisms that fine-tune the signal that is initiated at the cell surface following FGFR stimulation.

  19. Assessment of uterine shape and size using Kurz's Cavimeter.

    Science.gov (United States)

    de Castro, A

    1988-06-01

    The Kurz's Cavimeter was used to determine uterine shape and dimensions in 509 women prior to IUD insertion. The women were separated into six groups, depending on parity. A slight increase was noted in total uterine length due to endometrial cavity length and transverse fundal diameter in relationship to parity. However, the differences did not reach statistical significance.

  20. Morinda lucida reduces contractility of isolated uterine smooth ...

    African Journals Online (AJOL)

    Morinda lucida reduces contractility of isolated uterine smooth muscle of ... (OXY; 10-5–10-2 mol/L), acetylcholine (ACh; 10-9-10-5 mol/L) and M. lucida extract ... by L-NAME suggesting that the action of the compound on uterine muscle is not ...

  1. Non-puerperal uterine inversion: a case report

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    Anitha G.S.

    2015-08-01

    The aim was to highlight a rare condition of chronic non-puerperal uterine inversion following the extrusion of a benign fundally located submucous uterine myoma. A high index of suspicion is required to make a prompt diagnosis. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1223-1226

  2. Idiopathic prolapse of 1 uterine horn in a yearling filly

    Science.gov (United States)

    2004-01-01

    Abstract A yearling filly was presented for protrusion of a mass at the vulvar margins. A diagnosis of prolapse of the right uterine horn was made after vaginoscopy, transrectal palpation, and ultrasonography. It was confirmed later by biopsy of the tissue. Recovery was uneventful after easy replacement of the uterine horn. PMID:15317392

  3. Pregnancy with third degree uterine prolapse: a rare case report

    National Research Council Canada - National Science Library

    Latika; Smiti Nanda; Meenakshi Chauhan; Vani Malhotra

    2016-01-01

    .... Incidence of uterine prolapse in pregnancy is 1 in 10,000-15,000 deliveries worldwide. A 35 year old G5P3L1A1 with history of five months amenorrhea was referred to our hospital in view of uterine prolapse...

  4. CT-Monitored Percutaneous Cryoablation of Uterine Fibroids after Uterine Artery Embolization

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate the effects of percutaneous cryoablation on uterine fibroids using computed tomographic (CT) guidance after uterine artery embolization.METHODS Twelve patients who failed to respond to uterine artery embolization were treated using percutaneous cryoablation. All patients had undergone previous uterine artery embolization an average of 1.2 years (0.7~1.6 years) ago. Two cases had abnormal bleeding, and the other 10 suffered from pressure and/or pelvic pain. Myoma diameters were 4 cm to 16.5 cm. By using CT guidance, 2.0, 2.4, 3.0 or 3.8 mm cryoprobes were placed into the fibroid, and two 15~20 min freezing processes were performed. Hemostasis was achieved only by pressing the incisions for several minutes.MR-imaging was performed before the procedure to measure the size and number of fibroid tumors, and follow- up MR-imaging determined the reduction of the lesions.RESULTS All patients were discharged within 48 h of treatment. Almost no hemorrhage was found in all of the cases. No bladder or bowel injury or significant postsurgery pain was reported. Ice spheres were readily visualized at CT. Beam-hardening artifact from the metal probes was present, but did not interfere with the procedure. Myomas regressed up to 76.3% after 12 months of treatment, and the primary symptoms improved in all treated women.CONCLUSION CT-monitored percutaneous cryoablation is an effective and minimally invasive therapy for symptom relief and fibroid shrinkage after the failure of uterine artery embolization.

  5. Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy.

    Science.gov (United States)

    Zuliani, Thomas; Saiagh, Soraya; Knol, Anne-Chantal; Esbelin, Julie; Dréno, Brigitte

    2013-01-01

    Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors.

  6. Fetal Fibroblasts and Keratinocytes with Immunosuppressive Properties for Allogeneic Cell-Based Wound Therapy

    Science.gov (United States)

    Zuliani, Thomas; Saiagh, Soraya; Knol, Anne-Chantal; Esbelin, Julie; Dréno, Brigitte

    2013-01-01

    Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors. PMID:23894651

  7. Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into myofibroblasts.

    Science.gov (United States)

    Bai, Jian; Zhang, Na; Hua, Ying; Wang, Bingjian; Ling, Lin; Ferro, Albert; Xu, Biao

    2013-01-01

    Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that leads to pathological cardiac remodeling. Metformin, an antidiabetic agent, exhibits a number of cardioprotective properties. However, much less is known regarding the effect of metformin on cardiac fibroblast differentiation. Thus, in the present study, we examined the effect of metformin on angiotensin (Ang) II-induced differentiation of cardiac fibroblasts into myofibroblasts and its underlying mechanism. Adult rat cardiac fibroblasts were stimulated with Ang II (100 nM) in the presence or absence of metformin (10-200 µM). Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA) and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin. Metformin also decreased Ang II-induced reactive oxygen species (ROS) generation in cardiac fibroblasts via inhibiting the activation of the PKC-NADPH oxidase pathway. Further experiments using PKC inhibitor calphostin C and NADPH oxidase inhibitor apocynin confirmed that inhibition of the PKC-NADPH oxidase pathway markedly attenuated Ang II-induced ROS generation and myofibroblast differentiation. These data indicate that metformin inhibits Ang II-induced myofibroblast differentiation by suppressing ROS generation via the inhibition of the PKC-NADPH oxidase pathway in adult rat cardiac fibroblasts. Our results provide new mechanistic insights regarding the cardioprotective effects of metformin and provide an efficient therapeutic strategy to attenuate cardiac fibrosis.

  8. Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into myofibroblasts.

    Directory of Open Access Journals (Sweden)

    Jian Bai

    Full Text Available Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that leads to pathological cardiac remodeling. Metformin, an antidiabetic agent, exhibits a number of cardioprotective properties. However, much less is known regarding the effect of metformin on cardiac fibroblast differentiation. Thus, in the present study, we examined the effect of metformin on angiotensin (Ang II-induced differentiation of cardiac fibroblasts into myofibroblasts and its underlying mechanism. Adult rat cardiac fibroblasts were stimulated with Ang II (100 nM in the presence or absence of metformin (10-200 µM. Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin. Metformin also decreased Ang II-induced reactive oxygen species (ROS generation in cardiac fibroblasts via inhibiting the activation of the PKC-NADPH oxidase pathway. Further experiments using PKC inhibitor calphostin C and NADPH oxidase inhibitor apocynin confirmed that inhibition of the PKC-NADPH oxidase pathway markedly attenuated Ang II-induced ROS generation and myofibroblast differentiation. These data indicate that metformin inhibits Ang II-induced myofibroblast differentiation by suppressing ROS generation via the inhibition of the PKC-NADPH oxidase pathway in adult rat cardiac fibroblasts. Our results provide new mechanistic insights regarding the cardioprotective effects of metformin and provide an efficient therapeutic strategy to attenuate cardiac fibrosis.

  9. Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy.

    Directory of Open Access Journals (Sweden)

    Thomas Zuliani

    Full Text Available Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors.

  10. Uterine rotation: a cause of intestinal obstruction.

    Science.gov (United States)

    González-Mesa, Ernesto; Narbona, Isidoro; Cohen, Isaac; Villegas, Emilia; Cuenca, Celia

    2013-01-01

    Intestinal obstruction is an uncommon surgical emergency during pregnancy that affects seriously the prognosis of gestation. The underlying cause can be identified in the majority of cases and usually consists of adhesions secondary to previous abdominal or pelvic surgery, followed in order of frequency by intestinal volvuli. In recent years there have been no reports in which the gravid uterus has been the cause of intestinal obstruction. We report the case of a woman in week 33 + 4 of pregnancy who developed extrinsic compression of the colon secondary to uterine rotation and pelvic impaction of the head of the fetus.

  11. Subtotal Uterine Prolapse in Pregnancy and Management: Case Report

    Directory of Open Access Journals (Sweden)

    Atilla Karateke

    2015-11-01

    Full Text Available Uterine prolapse is usually an entity of elderly women and is very rare in pregnancy. Fetal and maternal complications can increase in pregnant women with uterine prolapse. In this article, we presented a woman who admitted to policlinic with complain of travail at the gestation of 33th week and was hospitalized to the hospital with diagnosis of uterine prolapse and preterm labor. A live female infant weighing 1750 gr was delivered via cesarean section because of unresponsive to medical therapy for preterm labor. It was observed that uterine prolapse was regressed spontaneously after a month of postpartum. Uterine prolapse, if seen in pregnancy, is an entity that should be careful in terms of fetal and maternal complications and treatment varies according to the patient.

  12. Synergistic Induction of Eotaxin and VCAM-1 Expression in Human Corneal Fibroblasts by Staphylococcal Peptidoglycan and Either IL-4 or IL-13

    Directory of Open Access Journals (Sweden)

    Ken Fukuda

    2011-01-01

    Conclusions: Interaction of innate and adaptive immunity, as manifested by synergistic stimulation of eotaxin and VCAM-1 expression in corneal fibroblasts by peptidoglycan and Th2 cytokines, may play an important role in tissue eosinophilia associated with ocular allergy.

  13. Effect of low-power red light laser irradiation on the viability of human skin fibroblast

    Energy Technology Data Exchange (ETDEWEB)

    Bednarska, K.; Rozga, B.; Leyko, W.; Bryszewska, M. [Institute of Biophysics, University of Lodz (Poland); Kolodziejczyk, K.; Szosland, D. [Diabetological Clinic, Medical Academy of Lodz (Poland)

    1998-10-01

    Human skin fibroblast monolayers (S-126 cell line) were exposed to laser radiation (wavelength 670 nm, power density 40 mW/cm{sup 2}). The energy densities were 2 J/cm{sup 2} and 12 J/cm{sup 2}, respectively, and the irradiation was carried out at a temperature of 22 C. For fibroblast viability evaluation, the colorimetric assay (conversion of thiazolyl blue to formazan) was used. The experiments were carried out at 37 C, in the presence of 5% CO{sub 2}, and at different time periods of incubation after irradiation (2, 4, 8 h and 1, 2, 3, 4, 5 days). The results indicated that there was a certain stimulating effect on the long-term proliferation of skin fibroblasts and that the stimulation proceeded in two stages, the first one 2 h and the second one 3 days post-irradiation. (orig.) With 4 figs., 2 tabs., 13 refs.

  14. Indocyanine green fluorescence imaging for evaluation of uterine blood flow in cynomolgus macaque.

    Directory of Open Access Journals (Sweden)

    Iori Kisu

    Full Text Available BACKGROUND: Uterine blood flow is an important factor in uterine viability, but the number of blood vessels required to maintain viability is uncertain. In this study, indocyanine green (ICG fluorescence imaging was used to examine uterine hemodynamics and vessels associated with uterine blood flow in cynomolgus macaque. METHODS: The uterus of a female cynomolgus macaque was cut from the vaginal canal to mimic a situation during trachelectomy or uterine transplantation surgery in which uterine perfusion is maintained only with uterine and ovarian vessels. Intraoperative uterine hemodynamics was observed using ICG fluorescence imaging under conditions in which various nutrient vessels were selected by clamping of blood vessels. A time-intensity curve was plotted using imaging analysis software to measure the T(max of uterine perfusion for selected blood vessel patterns. Open surgery was performed with the uterus receiving nutritional support only from uterine vessels on one side. The size of the uterus after surgery was monitored using transabdominal ultrasonography. RESULTS: The resulting time-intensity curves displayed the average intensity in the regions of the uterine corpus and uterine cervix, and in the entire uterus. Analyses of the uterine hemodynamics in the cynomolgus macaque showed that uterine vessels were significantly related to uterine perfusion (P=0.008, whereas ovarian vessels did not have a significant relationship (P=0.588. When uterine vessels were clamped, ovarian vessels prolonged the time needed to reach perfusion maximum. Postoperative transabdominal ultrasonography showed that the size of the uterus was not changed 2 months after surgery, with recovery of periodic menstruation. The cynomolgus macaque has got pregnant with favorable fetus well-being. CONCLUSION: Uterine vessels may be responsible for uterine blood flow, and even one uterine vessel may be sufficient to maintain uterine viability in cynomolgus macaque. Our

  15. Effect of TGF-β1 on the expression of collagen in rat atrial and ventricular fibroblasts

    Directory of Open Access Journals (Sweden)

    Fa-jin LIU

    2015-07-01

    Full Text Available Objective To observe the effect of transforming growth factor beta 1 (TGF-β1 on the expression of collagen in rat atrial and ventricular fibroblasts, and to investigate its specific molecular mechanisms. Methods Tissue explant attachment was used to culture fibroblasts obtained from the atrium and ventricle of rat heart, and they were identified with SABC immunocytochemical staining, and then the following experiments were carried out. (1 Hydroxyproline digestion was performed to study the effects of TGF-β1, within different concentrations (0, 5, 10ng/ml and different action time (6, 12, 24, 48h on the content of hydroxyproline in rat's atrial and ventricular fibroblasts. (2 Rat's atrial and ventricular fibroblasts were stimulated with TGF-β1 in optimal concentration and action time, the expression of α-smooth muscle actin (α-SMA was determined with Western blotting, and the expressions of typeⅠand Ⅲ collagen mRNA were evaluated with reverse-transcription PCR. The contents of hydroxyproline in the respective cells were measured with hydroxyproline determination. Western blotting was used to measure the protein expression of Smad2/3, p-Smad2/3 and Smad7. Results (1 TGF-β1 was shown to stimulate the collagen synthesis in rat's atrial and ventricular fibroblasts, and the optimal stimulus was TGF-β1 concentration 5ng/ml with action time of 24h. (2 After being stimulated by optimal stimulation effect of TGF-β1, the expression of typeⅠand Ⅲ collagen and p-Smad2/3 increased,while that of Smad7 decreased significantly only in atrial fibroblasts (P<0.05, but not in ventricular fibroblasts. No statistical difference was found in the expression of Smad2/3 between the atrial and ventricular fibroblasts after being stimulated by TGF-β1 under optimal stimulating conditions. Conclusion TGF-β1 can induce dysbolism of collagen of cardiac fibroblasts with abnormal expression of cytoskeletal protein, which may occur more obviously in rat

  16. The activity of cancer procoagulant in cases of uterine leiomyomas.

    Science.gov (United States)

    Jozwik, M; Szajda, S D; Skrzydlewski, Z; Jozwik, M; Sulkowski, S

    2005-01-01

    It is currently believed that cancer procoagulant (CP), an enzymatic protein, is a product of malignant neoplastic cells. The present study was designed to test whether it is also synthesized by benign neoplastic cells, namely uterine leiomyomas. We determined the activity of CP in the blood serum of women with uterine leiomyomas (N = 24), normal women (N = 15), and genital cancer patients (N = 6) by the coagulative method according to Gordon and Benson. Also, the CP activity in 10% tissue homogenates of uterine leiomyomas, normal uterine muscle and tissues of cervical and endometrial carcinoma was determined by the chromogenic method according to Colucci et al. The mean CP activity in the sera of women with uterine leiomyomas was 181.1 seconds (s) +/- 19.9 s, in healthy women--293.2 s +/- 33.8 s, and in genital cancer patients--78.8 +/- 18.5 s (all differences: p < 0.001). Similarly, in homogenates of uterine leiomyomas the CP activity was 19.6 +/- 3.8 nmoles pNa/ml, in normal uterine muscle it was 13.2 +/- 2.2 nmoles pNa/ml, and in cancerous tissue--28.0 +/- 6.6 nmol pNa/ml (all values being significantly different from each other). There was a strong correlation (r = -0.8122; p < 0.001) between the CP activity in uterine leiomyomas and serum activity, suggesting that the source of the serum CP activity was from the leiomyoma. The coagulation time of 120 to 240 s by the Gordon and Benson method supported the diagnosis of uterine leiomyoma, and a value below 120 s--the suspicion of genital cancer. Uterine leiomyomas, representing benign genital neoplasia, synthesize CP and are the likely origin of CP activity in blood, as has been described for malignant tumors, but to a lesser degree. There may be a role for CP as a tumor marker of genital neoplasia.

  17. LXA{sub 4} actions direct fibroblast function and wound closure

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, Bruno S. [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Leung, Kai P., E-mail: kai.p.leung.civ@mail.mil [Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Van Dyke, Thomas E., E-mail: tvandyke@forsyth.org [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States)

    2015-09-04

    Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A{sub 4} (LXA{sub 4}), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA{sub 4} on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA{sub 4} receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA{sub 4} receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA{sub 4} slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA{sub 4} tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA{sub 4} in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF

  18. Influence of mirena treatment on uterine blood flow dynamics and serum related indexes of patients with uterine adenomyosis

    Institute of Scientific and Technical Information of China (English)

    Qing-Yun Wang; Hua Zhang; Zhen-Zhen Liu

    2016-01-01

    Objective:To study the influence of mirena treatment on uterine blood flow dynamics and serum related indexes of patients with uterine adenomyosis.Methods:A total of 58 patients with uterine adenomyosis who were treated in our hospital during the time from June 2014 to July 2015 were randomly divided into two groups, 29 patients in the control group were treated with danazol, and 29 patients in the observation group were treated with mirena. Then the total effective rate, adverse reaction rates, uterine blood flow dynamics indexes, serum MMP related indexes and other disease related indexes of the two groups before the treatment and at first, third and sixth month after the treatment were compared.Results:The total effective rate and adverse reaction rate of observation group were both worse than that of control group (allP0.05). While the uterine blood flow dynamics indexes of the observation group at different time after the treatment were all significantly better than those of control group (allP<0.05).Conclusions:Mirena treatment can effectively improve the uterine blood flow dynamics and serum related indexes of patients with uterine adenomyosis, and it has application value for the patients with uterine adenomyosis is higher.

  19. Thin anterior uterine wall with incomplete uterine rupture in a primigravida detected by palpation and ultrasound: a case report

    Directory of Open Access Journals (Sweden)

    Usui Rie

    2011-01-01

    Full Text Available Abstract Introduction Uterine rupture is an obstetric complication associated with significant maternal and fetal morbidity and mortality. This disorder usually occurs with a scarred uterus, especially in a uterus with prior Cesarean section. Uterine sacculation or diverticulum may also lead to a thin uterine wall during pregnancy. Case presentation A 27-year-old Japanese primigravid woman was admitted to our hospital due to weak, irregular uterine contractions in her 38th week of gestation. She had no past history of uterine surgery or known diseases. A hard mass was palpable in her abdomen. An ultrasound revealed that the anterior uterine wall was thin and bulging, with a fetal minor part beneath it which corresponded to the palpated mass. A Cesarean section was performed which revealed a thin anterior uterine wall with incomplete uterine rupture. The woman and baby were healthy. Conclusions Although extremely rare, an unscarred primigravid uterus can undergo incomplete rupture even without discernable risk factors or labor pains. Abdominal palpation and ultrasound may be useful in detecting this condition.

  20. Impaired conversion of rat uterine estradiol receptors during aging.

    Science.gov (United States)

    Chuknyiska, R S; Justiniano, C; Roth, G S

    1986-01-01

    We have examined the effects of aging on the capacity of rat uterine estradiol receptors to be transformed from 8S to 4S and 5S species. Cytosol receptors from mature (6-month-old) rats or senescent (24-month-old) rats have been exposed to various KCl concentrations, ammonium sulfate precipitation and 25 degrees C heating. Estradiol receptors of both the mature and senescent age groups exist in an 8S form on linear 5-20% sucrose gradients in the absence of KCl and are converted to a 4S molecule in the presence of 0.4 M KCl. At intermediate salt concentrations a greater portion of mature receptors was converted to the 4S species. At 0.15 M KCl 62.3% +/- 2.8 of the mature receptors are converted to 4S versus 41% +/- 1.9 of the senescent receptors, and at 0.2 M KCl 79.6% +/- 3.2 of the mature receptors are converted to the 4S versus 58.2% +/- 2.1 of the senescent. Ammonium sulfate treatment in the presence of 0.3 M KCl converted about 80% of the receptors from the 4S to the 5S form, while only about half of the old receptors are affected. When ammonium sulfate precipitates were heated to 25 degrees C all to mature receptors were converted to the 5S species, while only two thirds of the senescent receptors were sedimented at 5S under the same conditions. Inclusion of 20 mM molybdate during preparation blocks conversion of about 15% of the senescent receptors from the 8S to the 4S form but does not affect the mature preparations. Similarly, molybdate treatment does not affect the conversion of the mature estradiol receptors to the 5S form but increases the percentage of senescent receptors remaining in the 4S form from 30 to 45%. Such qualitative differences in receptor conversion may be related to age associated deterioration of estradiol stimulated uterine responsiveness.

  1. IL-13 induces YY1 through the AKT pathway in lung fibroblasts.

    Science.gov (United States)

    Guo, Jia; Yao, Hongwei; Lin, Xin; Xu, Haodong; Dean, David; Zhu, Zhou; Liu, Gang; Sime, Patricia

    2015-01-01

    A key feature of lung fibrosis is the accumulation of myofibroblasts. Interleukin 13 (IL-13) is a pro-fibrotic mediator that directly and indirectly influences the activation of myofibroblasts. Transforming growth factor beta (TGF-β) promotes the differentiation of fibroblasts into myofibroblasts, and can be regulated by IL-13. However, IL-13's downstream signaling pathways are not completely understood. We previously reported that the transcription factor Yin Yang 1 (YY1) is upregulated in fibroblasts treated with TGF-β and in the lungs of mice and patients with pulmonary fibrosis. Moreover, YY1 directly regulates collagen and alpha smooth muscle actin (α-SMA) expression in fibroblasts. However, it is not known if IL-13 regulates fibroblast activation through YY1 expression. We hypothesize that IL-13 up-regulates YY1 expression through regulation of AKT activation, leading to fibroblast activation. In this study we found that YY1 was upregulated by IL-13 in lung fibroblasts in a dose- and time-dependent manner, resulting in increased α-SMA. Conversely, knockdown of YY1 blocked IL-13-induced α-SMA expression in fibroblasts. Furthermore, AKT phosphorylation was increased in fibroblasts treated with IL-13, and AKT overexpression upregulated YY1, whereas blockade of AKT phosphorylation suppressed the induction of YY1 by IL-13 in vitro. In vivo YY1 was upregulated in fibrotic lungs from CC10-IL-13 transgenic mice compared to that from wild-type littermates, which was associated with increased AKT phosphorylation. Taken together, these findings demonstrate that IL-13 is a potent stimulator and activator of fibroblasts, at least in part, through AKT-mediated YY1 activation.

  2. Enhanced Keratinocyte Proliferation and Migration in Co-culture with Fibroblasts

    Science.gov (United States)

    Wang, Zhenxiang; Wang, Ying; Farhangfar, Farhang; Zimmer, Monica; Zhang, Yongxin

    2012-01-01

    Wound healing is primarily controlled by the proliferation and migration of keratinocytes and fibroblasts as well as the complex interactions between these two cell types. To investigate the interactions between keratinocytes and fibroblasts and the effects of direct cell-to-cell contact on the proliferation and migration of keratinocytes, keratinocytes and fibroblasts were stained with different fluorescence dyes and co-cultured with or without transwells. During the early stage (first 5 days) of the culture, the keratinocytes in contact with fibroblasts proliferated significantly faster than those not in contact with fibroblasts, but in the late stage (11th to 15th day), keratinocyte growth slowed down in all cultures unless EGF was added. In addition, keratinocyte migration was enhanced in co-cultures with fibroblasts in direct contact, but not in the transwells. Furthermore, the effects of the fibroblasts on keratinocyte migration and growth at early culture stage correlated with heparin-binding EGF-like growth factor (HB-EGF), IL-1α and TGF-β1 levels in the cultures where the cells were grown in direct contact. These effects were inhibited by anti-HB-EGF, anti-IL-1α and anti-TGF-β1 antibodies and anti-HB-EGF showed the greatest inhibition. Co-culture of keratinocytes and IL-1α and TGF-β1 siRNA-transfected fibroblasts exhibited a significant reduction in HB-EGF production and keratinocyte proliferation. These results suggest that contact with fibroblasts stimulates the migration and proliferation of keratinocytes during wound healing, and that HB-EGF plays a central role in this process and can be up-regulated by IL-1α and TGF-β1, which also regulate keratinocyte proliferation differently during the early and late stage. PMID:22911722

  3. Enhanced keratinocyte proliferation and migration in co-culture with fibroblasts.

    Directory of Open Access Journals (Sweden)

    Zhenxiang Wang

    Full Text Available Wound healing is primarily controlled by the proliferation and migration of keratinocytes and fibroblasts as well as the complex interactions between these two cell types. To investigate the interactions between keratinocytes and fibroblasts and the effects of direct cell-to-cell contact on the proliferation and migration of keratinocytes, keratinocytes and fibroblasts were stained with different fluorescence dyes and co-cultured with or without transwells. During the early stage (first 5 days of the culture, the keratinocytes in contact with fibroblasts proliferated significantly faster than those not in contact with fibroblasts, but in the late stage (11(th to 15(th day, keratinocyte growth slowed down in all cultures unless EGF was added. In addition, keratinocyte migration was enhanced in co-cultures with fibroblasts in direct contact, but not in the transwells. Furthermore, the effects of the fibroblasts on keratinocyte migration and growth at early culture stage correlated with heparin-binding EGF-like growth factor (HB-EGF, IL-1α and TGF-β1 levels in the cultures where the cells were grown in direct contact. These effects were inhibited by anti-HB-EGF, anti-IL-1α and anti-TGF-β1 antibodies and anti-HB-EGF showed the greatest inhibition. Co-culture of keratinocytes and IL-1α and TGF-β1 siRNA-transfected fibroblasts exhibited a significant reduction in HB-EGF production and keratinocyte proliferation. These results suggest that contact with fibroblasts stimulates the migration and proliferation of keratinocytes during wound healing, and that HB-EGF plays a central role in this process and can be up-regulated by IL-1α and TGF-β1, which also regulate keratinocyte proliferation differently during the early and late stage.

  4. Effect of Arctium lappa (burdock) extract on canine dermal fibroblasts.

    Science.gov (United States)

    Pomari, Elena; Stefanon, Bruno; Colitti, Monica

    2013-12-15

    Although the biological activities of Arctium lappa (burdock) have been already investigated in human and other species, data evaluating the molecular mechanisms have not been reported in the dog. In this study we analyzed for the first time the effect of a root extract of burdock on molecular responses in canine dermal fibroblasts with H2O2 stimulation (H group), with burdock treatment (B group) and with H2O2 stimulation and burdock treatment (BH group), using RNAseq technology. Differentially expressed genes (P<0.05) of H, B and BH groups in comparison to the untreated sample (negative control, C group) were identified with MeV software and were functional annotated and monitored for signaling pathways and candidate biomarkers using the Ingenuity Pathways Analysis (IPA). The expression profile of canine dermal fibroblasts treated with burdock extract with or without H2O2 stimulation, showed an up-regulation of mitochondrial superoxide dismutase (SOD2), disheveled 3 (DVL3) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2). The data suggested that burdock has implications in cell adhesion and gene expression with the modulation of Wnt/β catenin signaling and Chondroitin Sulphate Biosynthesis that are particularly important for the wound healing process.

  5. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takao [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kibe, Toshiro [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Nishizawa, Yoshiaki [Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Hijioka, Hiroshi; Fujii, Tomomi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ueda, Masahiro [Natural Science Centre for Research and Education, Kagoshima University, 1-21-24 Koorimoto, Kagoshima 890-8580 (Japan); Nakamura, Norifumi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kiyono, Tohru [Department of Virology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuouku, Tokyo 104-0045 (Japan); Kishida, Michiko, E-mail: kmichiko@m2.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2014-09-05

    Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

  6. S100A4 amplifies TGF-β-induced fibroblast activation in systemic sclerosis

    DEFF Research Database (Denmark)

    Tomcik, Michal; Palumbo-Zerr, Katrin; Zerr, Pawel

    2015-01-01

    the expression of S100A4 to stimulate the release of collagen in SSc fibroblasts and induce fibrosis. Since S100A4 is essentially required for the pro-fibrotic effects of TGF-β and neutralising antibodies against S100A4 are currently evaluated, S100A4 might be a candidate for novel antifibrotic therapies....

  7. RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro

    NARCIS (Netherlands)

    Steenvoorden, M.M.C.; Toes, R.E.M.; Ronday, H.K.; Huizinga, T.W.J.; Groot, J. de

    2007-01-01

    Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristi

  8. RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro

    NARCIS (Netherlands)

    Steenvoorden, M.M.C.; Toes, R.E.M.; Ronday, H.K.; Huizinga, T.W.J.; Groot, J. de

    2007-01-01

    Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the

  9. RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro

    NARCIS (Netherlands)

    Steenvoorden, M.M.C.; Toes, R.E.M.; Ronday, H.K.; Huizinga, T.W.J.; Groot, J. de

    2007-01-01

    Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristi

  10. Reversal of Senescence in Mouse Fibroblasts through Lentiviral Suppression of p53

    NARCIS (Netherlands)

    Dirac, A.M.G.; Bernards, R.A.

    2003-01-01

    Senescence is generally defined as an irreversible state of G1 cell cycle arrest in which cells are refractory to growth factor stimulation. In mouse embryo fibroblasts (MEFs), induction of senescence requires the presence of p19ARF and p53, as genetic ablation of either of these genes allows escape

  11. Tumor-associated fibroblasts as "Trojan Horse" mediators of resistance to anti-VEGF therapy.

    Science.gov (United States)

    Francia, Giulio; Emmenegger, Urban; Kerbel, Robert S

    2009-01-06

    While targeting VEGF has shown success against a number of human cancers, drug resistance has resulted in compromised clinical benefits. In this issue of Cancer Cell, Crawford et al. (2009) report that tumors resistant to anti-VEGF therapy stimulate tumor-associated fibroblasts to express proangiogenic PDGF-C, implicating it as a potential therapeutic target.

  12. Relationship between gelatin concentrations in silk fibroin-based composite scaffolds and adhesion and proliferation of mouse embryo fibroblasts.

    Science.gov (United States)

    Orlova, A A; Kotlyarova, M S; Lavrenov, V S; Volkova, S V; Arkhipova, A Yu

    2014-11-01

    Porous scaffolds of silk fibroin and composite porous scaffolds with 10, 20, 30, 40, and 50% gelatin were made by the freezing-thawing method. The relationship between adhesion and proliferation rate mouse embryo fibroblast and the scaffold composition was studied by laser confocal scanning microscopy. Addition of gelatin to the scaffold structure stimulated adhesion and proliferation of mouse embryo fibroblasts; the optimal content of gelatin was 30%.

  13. A fibroblast-associated antigen: Characterization in fibroblasts and immunoreactivity in smooth muscle differentiated stromal cells

    DEFF Research Database (Denmark)

    Rønnov-Jessen, Lone; Celis, Julio E.; van Deurs, Bo

    1992-01-01

    Fibroblasts with smooth muscle differentiation are frequently derived from human breast tissue. Immunofluorescence cytochemistry of a fibroblast-associated antigen recognized by a monoclonal antibody (MAb), 1B10, was analyzed with a view to discriminating smooth muscle differentiated fibroblasts...... from vascular smooth muscle cells. The antigen was detected on the cell surface and in cathepsin D-positive and acridine orange-accumulating vesicular compartments of fibroblasts. Ultrastructurally, the antigen was revealed in coated pits and in endosomal and lysosomal structures. 1B10 recognized three...... immunoreactivity was specific to fibroblasts and smooth muscle differentiated fibroblasts within the context of vascular smooth muscle cells....

  14. Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: promising options for prevention and treatment of uterine fibroids?

    Science.gov (United States)

    Islam, Md Soriful; Akhtar, Most Mauluda; Ciavattini, Andrea; Giannubilo, Stefano Raffaele; Protic, Olga; Janjusevic, Milijana; Procopio, Antonio Domenico; Segars, James H; Castellucci, Mario; Ciarmela, Pasquapina

    2014-08-01

    Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70-80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids.

  15. Follistatin is critical for mouse uterine receptivity and decidualization.

    Science.gov (United States)

    Fullerton, Paul T; Monsivais, Diana; Kommagani, Ramakrishna; Matzuk, Martin M

    2017-06-13

    Embryo implantation remains a significant challenge for assisted reproductive technology, with implantation failure occurring in ∼50% of in vitro fertilization attempts. Understanding the molecular mechanisms underlying uterine receptivity will enable the development of new interventions and biomarkers. TGFβ family signaling in the uterus is critical for establishing and maintaining pregnancy. Follistatin (FST) regulates TGFβ family signaling by selectively binding TGFβ family ligands and sequestering them. In humans, FST is up-regulated in the decidua during early pregnancy, and women with recurrent miscarriage have lower endometrial expression of FST during the luteal phase. Because global knockout of Fst is perinatal lethal in mice, we generated a conditional knockout (cKO) of Fst in the uterus using progesterone receptor-cre to study the roles of uterine Fst during pregnancy. Uterine Fst-cKO mice demonstrate severe fertility defects and deliver only 2% of the number of pups delivered by control females. In Fst-cKO mice, the uterine luminal epithelium does not respond properly to estrogen and progesterone signals and remains unreceptive to embryo attachment by continuing to proliferate and failing to differentiate. The uterine stroma of Fst-cKO mice also responds poorly to artificial decidualization, with lower levels of proliferation and differentiation. In the absence of uterine FST, activin B expression and signaling are up-regulated, and bone morphogenetic protein (BMP) signals are impaired. Our findings support a model in which repression of activin signaling by FST enables uterine receptivity by preserving critical BMP signaling.

  16. A large uterine leiomyoma leading to non-puerperal uterine inversion: A case report

    Directory of Open Access Journals (Sweden)

    Batool Teimoori

    2017-08-01

    Full Text Available Background: Although leiomyomas are the most common gynecologic disorders, non-puerperal uterine inversion due to leiomyoma is considered as a rare clinical problem. This condition can occur as a complication of a large sub-mucous leiomyoma that leads to dilate cervix and protrude into vagina. The patient may have several symptoms such as heavy vaginal bleeding, pelvic pain and intermittent acute urinary retention. Case: We presented a 32-year-old nulliparous woman with 17 years of unexplained infertility and diagnosis of a large vaginal prolapsed non-pedunculated leiomyoma. Conclusion: Haultain’s procedure was used to reposition uterine inversion and remove leiomyoma through a posterior incision, using laparotomy

  17. Management options for women with uterine prolapse interested in uterine preservation.

    Science.gov (United States)

    Kow, Nathan; Goldman, Howard B; Ridgeway, Beri

    2013-10-01

    A variety of nonsurgical and surgical treatment options exist for the treatment of pelvic organ prolapse. While nonsurgical management is often selected as first-line treatment, many women eventually elect to undergo surgical management. Traditionally, prolapse repair often includes concomitant hysterectomy; however, women increasingly desire uterine preservation for a myriad of reasons. Multiple surgical procedures have been described to correct apical prolapse while preserving the uterus. Many studies suggest similar anatomic and functional outcomes compared to prolapse procedures with concomitant hysterectomy. Potential benefits include decreased operative time and avoidance of hysterectomy-specific complications, although there are several unique issues to consider if the uterus is retained. Surgeons must provide adequate counseling and preoperative evaluation before proceeding with uterine preservation.

  18. Induced and Spontaneous Abortion and Risk of Uterine Fibroids.

    Science.gov (United States)

    Song, Lulu; Shen, Lijun; Mandiwa, Chrispin; Yang, Siyi; Liang, Yuan; Yuan, Jing; Wang, Youjie

    2017-01-01

    The relationship between abortion and uterine fibroids has received little attention. The aim of the present study was to explore the association between number of induced and spontaneous abortions and the risk of uterine fibroids in middle-aged and older Chinese women. A total of 14,595 retired female employees from the Dongfeng-Tongji cohort study were included in our analysis. Information on induced and spontaneous abortions was collected by trained interviewers through face-to-face interviews. Diagnosis of uterine fibroids was based on ultrasound or self-reported physician diagnosis of uterine fibroids. Logistic regression models were used to explore the associations between number of induced and spontaneous abortions and the risk of uterine fibroids. The prevalence of uterine fibroids was 15.1% among all participants. Higher number of induced abortions was associated with an increased risk of uterine fibroids (1 induced abortion: odds ratios [ORs] = 1.32, 95% confidence interval [CI] 1.18-1.48; 2 induced abortions: OR = 1.45, 95% CI 1.28-1.64; and ≥3 induced abortions: OR = 1.62, 95% CI 1.39-1.90). Compared with women without induced abortion, ORs for women with 1, 2, and ≥3 were 1.17 (95% CI 1.03-1.32), 1.21 (95% CI 1.06-1.39), and 1.36 (95% CI 1.15-1.61), respectively, after adjustment for potential confounders. No association was observed between the number of spontaneous abortions and the risk of uterine fibroids. The findings of this study showed that induced abortion may be an independent risk factor for uterine fibroids in middle-aged and older Chinese women.

  19. Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

    Energy Technology Data Exchange (ETDEWEB)

    Togo, Shinsaku, E-mail: shinsaku@juntendo.ac.jp [Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Polanska, Urszula M. [CR-UK Stromal-Tumour Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Wilmslow Road, Manchester M20 4BX (United Kingdom); Horimoto, Yoshiya [Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Atopy Research Centre, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Department of Breast Oncology, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Orimo, Akira, E-mail: shinsaku@juntendo.ac.jp [CR-UK Stromal-Tumour Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Wilmslow Road, Manchester M20 4BX (United Kingdom); Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Atopy Research Centre, Juntendo University School of Medicine, Tokyo 113-8412 (Japan)

    2013-01-31

    Human carcinomas frequently exhibit significant stromal reactions such as the so-called “desmoplastic stroma” or “reactive stroma”, which is characterised by the existence of large numbers of stromal cells and extracellular matrix proteins. Carcinoma-associated fibroblasts (CAFs), which are rich in activated fibroblast populations exemplified by myofibroblasts, are among the predominant cell types present within the tumour-associated stroma. Increased numbers of stromal myofibroblasts are often associated with high-grade malignancies with poor prognoses in humans. CAF myofibroblasts possess abilities to promote primary tumour development, growth and progression by stimulating the processes of neoangiogenesis as well as tumour cell proliferation, survival, migration and invasion. Moreover, it has been demonstrated that CAFs serve as a niche supporting the metastatic colonisation of disseminated carcinoma cells in distant organs. Their contribution to primary and secondary malignancies makes these fibroblasts a potential therapeutic target and they also appear to be relevant to the development of drug resistance and tumour recurrence. This review summarises our current knowledge of tumour-promoting CAFs and discusses the therapeutic feasibility of targeting these cells as well as disrupting heterotypic interactions with other cell types in tumours that may improve the efficacy of current anti-tumour therapies.

  20. Responses of fibroblasts and glial cells to nanostructured platinum surfaces

    Science.gov (United States)

    Pennisi, C. P.; Sevcencu, C.; Dolatshahi-Pirouz, A.; Foss, M.; Lundsgaard Hansen, J.; Nylandsted Larsen, A.; Zachar, V.; Besenbacher, F.; Yoshida, K.

    2009-09-01

    The chronic performance of implantable neural prostheses is affected by the growth of encapsulation tissue onto the stimulation electrodes. Encapsulation is associated with activation of connective tissue cells at the electrode's metallic contacts, usually made of platinum. Since surface nanotopography can modulate the cellular responses to materials, the aim of the present work was to evaluate the 'in vitro' responses of connective tissue cells to platinum strictly by modulating its surface nanoroughness. Using molecular beam epitaxy combined with sputtering, we produced platinum nanostructured substrates consisting of irregularly distributed nanopyramids and investigated their effect on the proliferation, cytoskeletal organization and cellular morphology of primary fibroblasts and transformed glial cells. Cells were cultured on these substrates and their responses to surface roughness were studied. After one day in culture, the fibroblasts were more elongated and their cytoskeleton less mature when cultured on rough substrates. This effect increased as the roughness of the surface increased and was associated with reduced cell proliferation throughout the observation period (4 days). Morphological changes also occurred in glial cells, but they were triggered by a different roughness scale and did not affect cellular proliferation. In conclusion, surface nanotopography modulates the responses of fibroblasts and glial cells to platinum, which may be an important factor in optimizing the tissue response to implanted neural electrodes.

  1. Hydrogen sulfide suppresses transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts.

    Science.gov (United States)

    Zhang, YouEn; Wang, JiaNing; Li, Hua; Yuan, LiangJun; Wang, Lei; Wu, Bing; Ge, JunBo

    2015-11-01

    In heart disease, transforming growth factor-β1 (TGF-β1) converts fibroblasts into myofibroblasts, which synthesize and secrete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide (H2S) suppresses TGF-β1-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were serum-starved in fibroblast medium for 16 h before exposure to TGF-β1 (10 ng mL(-1)) for 24 h with or without sodium hydrosulfide (NaHS, 100 µmol L(-1), 30 min pretreatment) treatment. NaHS, an exogenous H2S donor, potently inhibited the proliferation and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NaHS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S suppresses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.

  2. A new laparoscopic technique for uterine prolapse: one-sided uterine fixation through the round ligament.

    Science.gov (United States)

    Hsieh, Ching-Hung

    2011-02-01

    In this study, we provide a description of laparoscopic uterine suspension technique through round ligament. From 1997 to 2010, 55 patients with uterine prolapse were treated by laparoscopic uterine suspension. It is performed by suturing and tying a 1-0 Ethibond on the left round ligament at its insertion into the uterus. Then curved forceps pass the lateral puncture wound into the extraperitoneal space along the round ligament and penetrates the anterior leaf of the broad ligament into the peritoneal cavity and grasps the free ends of the Ethibond. They are withdrawn extraperitoneally along the round ligament then tightly tied at the fasciae on either side of the lateral puncture wound. Forty-two out of 55 patients (76.4%) experienced a reduction of prolapse to stage 0, regardless of what stage they started from. Twelve out of 55 (21.8%) experienced a reduction of prolapse varying from one to two stages. One out of 55 (1.8%) experienced no reduction in prolapse. This technique reconstructs a new, inelastic round ligament.

  3. Diffusion-weighted MR imaging of uterine leiomyomas following uterine artery embolization

    Energy Technology Data Exchange (ETDEWEB)

    Sutter, Olivier; Shotar, Eimad; Guerrache, Youcef; Place, Vinciane; Oprea, Raluca; Le Dref, Olivier; Boudiaf, Mourad [Hopital Lariboisiere, AP-HP, Department of Body and Interventional Imaging, Paris (France); Soyer, Philippe; Dohan, Anthony [Hopital Lariboisiere, AP-HP, Department of Body and Interventional Imaging, Paris (France); Universite Paris-Diderot, Sorbonne Paris Cite, Paris (France); UMR INSERM 965, Hopital Lariboisiere, Paris (France); Dautry, Raphael; Sirol, Marc [Hopital Lariboisiere, AP-HP, Department of Body and Interventional Imaging, Paris (France); Universite Paris-Diderot, Sorbonne Paris Cite, Paris (France); Ricbourg, Aude [Hopital Lariboisiere-AP-HP, Department of Obstetrics and Gynecology, Paris (France)

    2016-10-15

    To test whether variations in apparent diffusion coefficient (ADC) values of uterine leiomyomas after uterine artery embolization (UAE) may correlate with outcome and assess the effects of UAE on leiomyomas and normal myometrium with magnetic resonance imaging (MRI). Data of 49 women who underwent pelvic MRI before and after UAE were retrospectively reviewed. Uterine and leiomyoma volumes, ADC values of leiomyomas, and normal myometrium were calculated before and after UAE. By comparison with baseline ADC values, a significant drop in leiomyoma ADC was found at 6-month post-UAE (1.096 x 10{sup -3} mm{sup 2}/s vs. 0.712 x 10{sup -3} mm{sup 2}/s, respectively; p < 0.0001), but not at 48-h post-UAE. Leiomyoma devascularization was complete in 40/49 women (82 %) at 48 h and in 37/49 women (76 %) at 6 months. Volume reduction and leiomyoma ADC values at 6 months correlated with the degree of devascularization. There was a significant drop in myometrium ADC after UAE. Perfusion defect of the myometrium was observed at 48 h in 14/49 women (28.5 %) in association with higher degrees of leiomyoma devascularization. Six months after UAE, drop in leiomyoma ADC values and volume reduction correlate with the degree of leiomyoma devascularization. UAE affects the myometrium as evidenced by a drop in ADC values and initial myometrial perfusion defect. (orig.)

  4. Intrauterine tamponade balloon use in the treatment of uterine inversion.

    Science.gov (United States)

    Haeri, Sina; Rais, Sheliza; Monks, Brian

    2015-01-06

    Uterine inversion is a rare but life-threatening obstetrical emergency that occurs when the fundus of the uterus prolapses through the cervix, hence turning the uterus inside out. In this case report, we present our experience using an intrauterine tamponade balloon for management of uterine inversion, and a review of the literature. The utility of an intrauterine tamponade balloon in cases of uterine inversion, especially when maternal medical conditions preclude the use of uterotonics, or reinversion is observed should be kept in mind.

  5. Uterine Arteriovenous Malformation with Sudden Heavy Vaginal Hemmorhage

    Directory of Open Access Journals (Sweden)

    Marianne Haughey

    2013-09-01

    Full Text Available Dysfunctional uterine bleeding (DUB is a common presentation in the emergency department and has a wide differential. Most presentations of DUB are in hemodynamically stable patients and can be evaluated as an outpatient. Uterine arteriovenous malformation (AVM is one presentation that can result in a life-threatening medical emergency with unexpected sudden and massive vaginal bleeding. We describe a case of a 24-year-old female with sudden heavy vaginal bleeding requiring a blood transfusion, ultrasound evidence of uterine AVM, and a treatment method of expectant management using an intrauterine device in an attempt to preserve fertility. [West J Emerg Med. 2013;14(5:411-414.

  6. Biopsy of uterine leiomyomata and frozen sections before laparoscopic morcellation.

    Science.gov (United States)

    Tulandi, Togas; Ferenczy, Alex

    2014-01-01

    Uterine sarcoma is rare. However, its morcellation can be associated with spread of disease. The definitive diagnosis of uterine sarcomas is made via histology. To date, the only reliable preoperative test for determination of the types of myometrial tumors is analysis of either frozen sections or permanent formalin-fixed tissue sections of surgical specimens. We report 2 cases in which the feasibility of obtaining multiple biopsy specimens of uterine leiomyomas and frozen sections before laparoscopic morcellation is demonstrated. This procedure might reduce the risk of laparoscopic morcellation of unsuspected leiomyosarcomas while still offering the advantages of a minimally invasive technique.

  7. Modulation of human uterine smooth muscle cell collagen contractility by thrombin, Y-27632, TNF alpha and indomethacin

    Directory of Open Access Journals (Sweden)

    Smith Terry J

    2009-01-01

    Full Text Available Abstract Background Preterm labour occurs in approximately 10% of pregnancies and is a major cause of infant morbidity and mortality. However, the pathways involved in regulating contractility in normal and preterm labour are not fully elucidated. Our aim was to utilise a human myometrial contractility model to investigate the effect of a number of uterine specific contractility agents in this system. Therefore, we investigated the contractile response of human primary uterine smooth muscle cells or immortalised myometrial smooth muscle cells cultured within collagen lattices, to known mediators of uterine contractility, which included thrombin, the ROCK-1 inhibitor Y-27632, tumour necrosis factor alpha (TNF alpha and the non-steroidal anti-inflammatory indomethacin. Methods Cell contractility was calculated over time, with the collagen gel contraction assay, utilising human primary uterine smooth muscle cells (hUtSMCs and immortalised myometrial smooth muscle cells (hTERT-HM: a decrease in collagen gel area equated to an increase in contractility. RNA was isolated from collagen embedded cells and gene expression changes were analysed by real time fluorescence reverse transcription polymerase chain reaction. Scanning electron and fluorescence microscopy were employed to observe cell morphology and cell collagen gel interactions. Statistical analysis was performed using ANOVA followed by Tukey's post hoc tests. Results TNF alpha increased collagen contractility in comparison to the un-stimulated collagen embedded hUtSMC cells, which was inhibited by indomethacin, while indomethacin alone significantly inhibited contraction. Thrombin augmented the contractility of uterine smooth muscle cell and hTERT-HM collagen gels, this effect was inhibited by the thrombin specific inhibitor, hirudin. Y-27632 decreased both basal and thrombin-induced collagen contractility in the hTERT-HM embedded gels. mRNA expression of the thrombin receptor, F2R was up

  8. Effects of chlorhexidine, essential oils and herbal medicines (Salvia, Chamomile, Calendula) on human fibroblast in vitro.

    Science.gov (United States)

    Wyganowska-Swiatkowska, Marzena; Urbaniak, Paulina; Szkaradkiewicz, Anna; Jankun, Jerzy; Kotwicka, Malgorzata

    2016-01-01

    Antiseptic rinses have been successfully used in inflammatory states of the gums and oral cavity mucosa. Antibacterial effects of chlorhexidine, essential oils and some herbs are well documented. Reaction of host tissue to these substances has much poorer documentation. The aim of the study was to analyse the influence of chlorhexidine (CHX), essential oil (EO: thymol, 0.064%; eucalyptol, 0.092%; methyl salicylate, 0.060%; menthol, 0.042%) mouth rinses and salvia, chamomile and calendula brews on fibroblast biology in vitro. The human fibroblast CCD16 line cells were cultured in incubation media which contained the examined substances. After 24 and 48 hours, the cell morphology, relative growth and apoptosis were evaluated. Exposure of fibroblasts to CHX, EO or salvia caused various changes in cell morphology. Cells cultured for 48 hours with CHX revealed a noticeably elongated shape of while cells cultured in high EO concentration or with salvia were considerably smaller and contracted with fewer projections. Chlorhexidine, EO and salvia reduced the fibroblast proliferation rate and stimulated cell death. Both reactions to EO were dose dependent. Cells exposure to chamomile or calendula brews did not change morphology or proliferation of fibroblasts. The results of this in vitro study showed that in contrast to chamomile and calendula, the brews of EO, CHX or salvia had a negative influence on fibroblast biology.

  9. Pentadecapeptide BPC 157 Enhances the Growth Hormone Receptor Expression in Tendon Fibroblasts

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    Chung-Hsun Chang

    2014-11-01

    Full Text Available BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon.

  10. Glucocorticoid receptors in fibroblasts from synovial tissue. Changes during the inflammatory process. Preliminary results.

    Science.gov (United States)

    Damon, M; Rabier, M; Loubatiere, J; Blotman, F; Crastes de Paulet, A

    1986-03-01

    There is known to be a significant correlation between the number of glucocorticoid receptors in tissues and their anti-inflammatory effect. In this work, the specific binding of glucocorticoids was studied in inflammatory fibroblasts. Human fibroblasts were obtained from the knee joint of a rheumatoid patient undergoing surgery; experimental fibroblasts were from rat granulomas. The same study was carried out in quiescent synovial fibroblasts from a healthy subject (post-traumatic amputation) and from rat subcutaneous conjunctive tissue. Fibroblasts were obtained by explant cultures and subcultures in monolayers. The stimulation state of cells was evaluated by the amounts of PGE2 and PGF2 alpha released into the culture media. Analysis of the proportions of steroid bound to whole cells showed evidence of specific glucocorticoid receptors in all fibroblasts. Their number was three times higher in cells from inflammatory tissues than from controls. This increased number of receptors in inflammatory cells could be the result of the action of one or more mediators that promote their biosynthesis.

  11. Deletion of the homeobox gene PRX-2 affects fetal but not adult fibroblast wound healing responses.

    Science.gov (United States)

    White, Philip; Thomas, David W; Fong, Steven; Stelnicki, Eric; Meijlink, Fritz; Largman, Corey; Stephens, Phil

    2003-01-01

    The phenotype of fibroblasts repopulating experimental wounds in vivo has been shown to influence both wound healing responses and clinical outcome. Recent studies have demonstrated that the human homeobox gene PRX-2 is strongly upregulated in fibroblasts within fetal, but not adult, mesenchymal tissues during healing. Differential homeobox gene expression by fibroblasts may therefore be important in mediating the scarless healing exhibited in early fetal wounds. RNase protection analysis demonstrated that murine Prx-2 expression was involved in fetal but not adult wound healing responses in vitro. Using fibroblasts established from homozygous mutant (Prx-2-/-) and wild-type (Prx-2+/+) murine skin tissues it was demonstrated that Prx-2 affected a number of fetal fibroblastic responses believed to be important in mediating scarless healing in vivo; namely cellular proliferation, extracellular matrix reorganization, and matrix metalloproteinase 2 and hyaluronic acid production. These data demonstrate how Prx-2 may contribute to the regulation of fetal, but not adult, fibroblasts and ultimately the wound healing phenotype. This study provides further evidence for the importance of homeobox transcription factors in the regulation of scarless wound healing. A further understanding of these processes will, it is hoped, enable the targeting of specific therapies in wound healing, both to effect scarless healing and to stimulate healing in chronic, nonhealing wounds such as venous leg ulcers.

  12. Intestinal adhesion due to previous uterine surgery as a risk factor for delayed diagnosis of uterine rupture: a case report

    Directory of Open Access Journals (Sweden)

    Usui Rie

    2011-10-01

    Full Text Available Abstract Introduction Uterine rupture is a life-threatening condition both to mothers and fetuses. Its early diagnosis and treatment may save their lives. Previous myomectomy is a high risk factor for uterine rupture. Intestinal adhesion due to previous myomectomy may also prevent early diagnosis of uterine rupture. Case presentation A 38-year-old primiparous non-laboring Japanese woman with a history of myomectomy was admitted in her 34th week due to lower abdominal pain. Although the pain was slight and her vital signs were stable, computed tomography revealed massive fluid collection in her abdominal cavity, which led us to perform a laparotomy. Uterine rupture had occurred at the site of the previous myomectomy; however, the small intestine was adhered tightly to the rupture, thus masking it. The baby was delivered through a low uterine segment transverse incision. The ruptured uterine wall was reconstructed. Conclusion Intestinal adhesion due to a prior myomectomy occluded a uterine rupture, possibly masking its symptoms and signs, which may have prevented early diagnosis.

  13. Effects of intra-uterine and early extra-uterine malnutrition on seizure threshold and hippocampal morphometry of pup rats.

    Science.gov (United States)

    Florian, Mariana Lorenzet; Nunes, Magda Lahorgue

    2010-12-01

    We evaluate the influence of different malnutrition paradigms (intra-uterine × extra-uterine) in body and brain weight, in seizure threshold and in hippocampus morphometry, in developing rats. Intra-uterine malnutrition model consisted in reduction by half of the ration offered to pregnant female; extra-uterine malnutrition consisted of progressive limitation of lactation, from P2 to P15. Seizure induction was accomplished by exposure to flurothyl, at P15. At the same day animals were sacrificed. Morphometric analysis was based on hippocampal pyramidal and granular cells estimate number, through volume calculation and cellular density. Extra-uterine malnutrition significantly reduced pups body and brain weight, seizure threshold and neuronal number in CA4 region only. Intra-uterine malnutrition reduced neuronal number in CA2, CA4 and DG regions regarding well-nourished and extra-uterine malnourished animals. In CA3, CA4 and dentate gyrus, a significant cell increase was observed in groups exposed to seizures, regarding similar control groups.

  14. Uterine artery flow velocity waveforms during uterine contractions: differences between oxytocin-induced contractions and spontaneous labor contractions.

    Science.gov (United States)

    Tahara, Mie; Nakai, Yuichiro; Yasui, Tomoyo; Nishimoto, Sachiyo; Nakano, Akemi; Matsumoto, Makiko; Nobeyama, Hiroyuki; Nishihara, Rika; Iwanaga, Naoko; Ishiko, Osamu

    2009-10-01

    To clarify the effects on uterine arterial flow velocity waveforms of uterine contractions following oxytocin infusion and during spontaneous labor. Uterine arterial flow velocity waveforms were obtained by pulsed Doppler methods from 22 women during an oxytocin challenge test (OCT), 26 women during oxytocin-induced labor, and 40 women during spontaneous labor. Mean resistance index (RI) for bilateral arteries was used for analyses. After the onset of labor, flow velocity waveforms were assessed according to cervical dilatation. During OCT, Doppler flow velocimetry was performed when three uterine contractions occurred per 10-min period. RI values did not differ significantly between induced and spontaneous labor during relaxations at any level of cervical dilatation. However, during contractions, RI was significantly higher for induced labor than for spontaneous labor. Absence or reversal of flow was more frequent in the OCT group than in the induced labor group (P labor groups. Interactions between the contracting uterine body and the relaxing lower segment in oxytocin-induced labor might be associated with differences in uterine arterial flow during contraction between oxytocin-induced and spontaneous labor. However, changes in the intensity of uterine contractions during labor progression might differ between oxytocin-induced and spontaneous labor.

  15. Polypropylene mesh as an alternative option for uterine preservation in pelvic reconstruction in patients with uterine prolapse.

    Science.gov (United States)

    Huang, Kuan-Hui; Chuang, Fei-Chi; Fu, Hung-Chun; Kung, Fu-Tsai

    2012-01-01

      The aim of this study was to evaluate the efficacy and safety of polypropylene mesh for uterine preservation during pelvic reconstruction in patients with severe uterine prolapse. The study included 67 women with severe uterine prolapse (pelvic organ prolapse quantification stage III/IV) who received transvaginal mesh reconstruction with uterine preservation. Surgery combined with a transobturator membrane sling procedure (tension-free vaginal tape-transobturator route) was performed in 54 patients. Among them, 18 had urodynamic stress incontinence, 30 had occult stress urinary incontinence, and six had mixed urinary incontinence. Objective assessments were carried out with the pelvic organ prolapse quantification staging system, urodynamic examination, and 1-h pad test. Evaluation of urinary and prolapse symptoms comprised the subjective assessment. The mean follow-up interval was 19.6 months (12-40 months). The objective cure rate for the treatment of uterine prolapse was 89.5%, and the objective cure rate for the treatment of urinary incontinence was more than 90%. Uterine preservation in pelvic reconstruction is technically feasible and the subjective and objective assessments imply that uterine preservation in pelvic reconstruction is an alternative option for indicated patients. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

  16. Abnormal uterine bleeding: a clinicohistopathological analysis

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    Anupamasuresh Y

    2014-06-01

    Methods: In our prospective study of 359 Patients of the age between 46 and 73 years, clinical characteristics and the pattern of endometrial histopathology and their association in women, who present with abnormal uterine bleeding, are categorised into six groups. Results: In our study, a significant correlation of histopathology and BMI was observed with endometrial hyperplasia and malignancy in obese patient i.e. 37 out 96 and 13 out of 23 respectively. The incidence of malignancy has been increasing with the age being 1.6% in 46-50 years to 60% in 70-75 years. In our study 116 (32.3% had hypertension, 33 patients (9.2% had diabetes mellitus, 40 patients (11.1% had hypothyroidism. Conclusions: We found a maximum incidence of AUB in multiparous women. Clinicohistopathological analysis of AUB revealed endometrial hyperplasia in majority of patients. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 656-661

  17. Non-communicating Rudimentary Uterine Horn Pregnancy

    Directory of Open Access Journals (Sweden)

    I Upadhyaya

    2011-12-01

    Full Text Available Pregnancy in a non-communicating rudimentary horn is an extremely rare form of ectopic gestation. The rudimentary horn may or may not communicate with the uterine cavity with the majority of cases being non-communicating. The patient exhibits features of acute abdomen and carries a high risk of maternal death. Even modern scans remain elusive whereas laparatomy remains the confi rmatory procedure for the diagnosis. Because of the varied muscular constitution in the thickness and distensibility of the wall of the rudimentary horn, pregnancy is accommodated for a variable period of gestation. Here, we report three cases of pregnancy in a non-communicating rudimentary horn of the uterus in different periods of gestation, their outcome and a review of the available literature. Keywords: Mullerian anomalies, non-communicating rudimentary horn pregnancy, surgical management.

  18. Lipoleiomyoma: A rare variant of uterine leiomyoma

    Directory of Open Access Journals (Sweden)

    D Manimaran

    2014-01-01

    Full Text Available Uterine fatty tumors are rare variants of benign leiomyoma. Lipoleiomyoma, lipomyoma, fibromyolipoma are various synonyms for this lesion. They usually occur in the obese perimenopausal and postmenopausal females in the age group 50-70 years and 90% cases occur in patients older than 40 years. There were only few cases reported in the literature. These lesions are interesting due to the occasional diagnostic confusion with sarcomas and the curiosity regarding its histogenesis. We are presenting three cases of lipoleiomyoma whose age ranged from 40 to 50 years with clinical, radiologic and pathologic correlation. All three cases came with complaints of abnormal vaginal bleeding and found to have intramural heteroechoic nodule in the ultrasonogram.

  19. The effects of twin pregnancy on uterine pull tension%双胎妊娠对子宫牵张力影响的研究

    Institute of Scientific and Technical Information of China (English)

    陶志云; 张晓慧; 张英; 魏兆莲

    2016-01-01

    Objective To study the effects of the uterine contraction when the uterine pull tension of twin pregnan-cy has changed. Methods The uterine smooth muscle of single and twin pregnant women in the second trimester of pregnancy (26 ± 6) W and late pregnancy(37 ± 6) W were collected to be made into 30 strips each group, ob-served the change of uterine pull tension of single and twin pregnancy and the effects to uterine contraction, when oxytocin concentration gradient was stimulated. Results In Krebs solution, the uterine pull tension of late single pregnancy was bigger than that in the second trimester, and the uterine pull tension of late twin pregnancy was big-ger than that in the second trimester, and the uterine pull tension of the second trimester of twin pregnancy was big-ger than that of single pregnancy at the same time, and the uterine pull tension of late twin pregnancy was bigger than that of single pregnancy at the same time. There was statistical significance (P<0. 05). With the progress of pregnancy, the uterine pull tension was enlarged. Moreover, the uterine contraction of late single pregnancy caused by the change of uterine pull tension was more obvious than that of late twin pregnancy under the oxytocin concen-tration gradient. There was statistical significance (P<0. 05). Conclusion The uterine contraction begins to de-cline with the uterine pull tension of twin pregnancy increases.%目的 探讨双胎妊娠子宫牵张力变化对子宫收缩能力的影响. 方法 采集单胎妊娠及双胎妊娠孕妇中期妊娠(孕26 ± 6周)和晚期妊娠(孕37 ± 6 周)的子宫平滑肌组织,制作成肌条各30份,给予缩宫素浓度梯度刺激,观察单胎妊娠与双胎妊娠的子宫牵张力变化及对子宫收缩力的影响. 结果 在Krebs液中,单胎妊娠晚孕阶段子宫牵张力大于中孕阶段,双胎妊娠晚孕阶段子宫牵张力大于中孕阶段,中孕阶段的双胎妊娠子宫牵张力大于单胎妊娠,晚孕阶段的双

  20. Transvaginal color Doppler imaging of uterine contractions in early pregnancies: Significance of uterine contractions in early pregnancy failure

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju; Han, Chang Jin; Suh, Jung Ho; Kwon, Hyuck Chan [Aju University SChool of Medicine, Suwon (Korea, Republic of)

    1999-06-15

    To assess uterine contractions in early pregnancies using transvaginal color Doppler sonography (TVCDS) and to determine the role of uterine contractions in the diagnosis of early pregnancy failure. 76 patients with abnormal pregnancy diagnosed by sonography or histopathology up to 10 weeks of gestation and 38 normal pregnant women as the control group were examines with TVCDS. The presence of uterine contractions was determined by complete or partial disappearance of the color flow signals of vessels within myometrium, and the direction, amplitude (grade 1-3), and interval of uterine contractions were also evaluated. Uterine contractions were identified in 42 (55.3%) of 76 patients with abnormal pregnancy, whereas they were detected only in 2 (5.3%) of 38 normal pregnant women who had initial grade 1 contraction but disappeared in the follow-up study. In 26 patients with blighted ovum or missed abortion, 15 patients (57.7%),showed uterine contraction of grade 1 in 3 cases, grade 2 in 8 cases, and grade 3 in 4 cases and interval from 45 seconds to 5 minutes. In 30 patients with inevitable or incomplete abortion, 23 patients (76.6%) showed uterine contraction of grade 1 in 2 cases, grade 2 in 9 cases, and grade 3 in 12 cases and interval from 1 to 5 minutes. 4 (20%) of 20 patients with threatened abortion had uterine contraction of grade 2 and interval from 2 to 4 minutes. The presence of uterine contractions was significantly different in abnormal pregnancies compared with that of normal and also among the tree different groups of abnormal pregnancies, but the amplitude did not differ.

  1. Anterior vaginal wall suspension procedure for moderate bladder and uterine prolapse as a method of uterine preservation.

    Science.gov (United States)

    Coskun, Burhan; Lavelle, Rebecca S; Alhalabi, Feras; Christie, Alana L; Zimmern, Philippe E

    2014-11-01

    We report our experience with anterior vaginal wall suspension for moderate anterior vaginal compartment prolapse and uterine descent less than stage 2. Data on patients who underwent anterior vaginal wall suspension with uterine preservation by hysteropexy and had a 1-year minimum followup were extracted from a long-term, prospective, institutional review board approved, surgical prolapse database. The indication for uterine preservation was uterine descent not beyond the distal third of the vagina with traction with the patient under anesthesia, and negative Pap smear and pelvic ultrasound preoperatively. The upper suture of the anterior vaginal wall suspension secures the cardinal ligament complex, allowing for uterine suspension once the suture is transferred suprapubically. Failure was defined as prolapse recurrence greater than stage 2 on physical examination or the need for reoperation for uterine descent. Outcome measures at serial intervals included validated questionnaires, physical examination, standing voiding cystourethrogram at 6 months postoperatively and complications. From May 1996 to March 2012, 52 of 739 patients met inclusion criteria. Mean followup was 55 months (range 12 to 175, median 44). Mean patient age was 62 years (range 38 to 81), mean body mass index was 26.7 kg/m(2) (range 18.3 to 49.4) and mean parity was 2.7. There were no transfusions or intraoperative complications. Overall 7 (13%) patients underwent subsequent hysterectomy for uterine prolapse recurrence at 7 months to 6 years postoperatively. The anterior vaginal wall suspension procedure offers a simple, mesh-free surgical alternative with acceptable long-term followup in patients with moderate uterine prolapse who wish for uterine preservation. However, patients should be appropriately counseled about the low risk of subsequent hysterectomy. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Lithium Attenuates TGF-β1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients

    Directory of Open Access Journals (Sweden)

    Marta Michalik

    2012-01-01

    Full Text Available Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β1-induced fibroblast to myofibroblast transition (FMT in HBF and found that the inhibition of GSK-3β attenuates TGF-β1-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β1/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases.

  3. Cardiac fibroblast in development and wound healing.

    Science.gov (United States)

    Deb, Arjun; Ubil, Eric

    2014-05-01

    Cardiac fibroblasts are the most abundant cell type in the mammalian heart and comprise approximately two-thirds of the total number of cardiac cell types. During development, epicardial cells undergo epithelial-mesenchymal-transition to generate cardiac fibroblasts that subsequently migrate into the developing myocardium to become resident cardiac fibroblasts. Fibroblasts form a structural scaffold for the attachment of cardiac cell types during development, express growth factors and cytokines and regulate proliferation of embryonic cardiomyocytes. In post natal life, cardiac fibroblasts play a critical role in orchestrating an injury response. Fibroblast activation and proliferation early after cardiac injury are critical for maintaining cardiac integrity and function, while the persistence of fibroblasts long after injury leads to chronic scarring and adverse ventricular remodeling. In this review, we discuss the physiologic function of the fibroblast during cardiac development and wound healing, molecular mediators of activation that could be possible targets for drug development for fibrosis and finally the use of reprogramming technologies for reversing scar. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium." Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5‐year results

    National Research Council Canada - National Science Library

    Moss, JG; Cooper, KG; Khaund, A; Murray, LS; Murray, GD; Wu, O; Craig, LE; Lumsden, MA

    2011-01-01

    .... Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5‐year results. BJOG 2011;118:936–944. Objective...

  5. Redirecting valvular myofibroblasts into dormant fibroblasts through light-mediated reduction in substrate modulus.

    Science.gov (United States)

    Wang, Huan; Haeger, Sarah M; Kloxin, April M; Leinwand, Leslie A; Anseth, Kristi S

    2012-01-01

    Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM) homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young's modulus of the substrate was reduced from ~32 kPa, mimicking pre-calcified diseased tissue, to ~7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA) stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF)) were significantly down-regulated to fibroblast levels within 6 hours of in situ substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in designing

  6. Redirecting valvular myofibroblasts into dormant fibroblasts through light-mediated reduction in substrate modulus.

    Directory of Open Access Journals (Sweden)

    Huan Wang

    Full Text Available Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young's modulus of the substrate was reduced from ~32 kPa, mimicking pre-calcified diseased tissue, to ~7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF were significantly down-regulated to fibroblast levels within 6 hours of in situ substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in

  7. Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma.

    Science.gov (United States)

    Lim, Kue Peng; Cirillo, Nicola; Hassona, Yazan; Wei, Wenbin; Thurlow, Johanna K; Cheong, Sok Ching; Pitiyage, Gayani; Parkinson, E Ken; Prime, Stephen S

    2011-03-01

    Oral cancer is a highly aggressive malignancy with poor prognosis. This study examined the behaviour of fibroblast strains from normal oral mucosa, dysplastic epithelial tissue, and genetically stable (minimal copy number alterations-CNA; minimal loss of heterozygosity-LOH; wild-type p53; wild-type p16INK4A) and unstable (extensive CNA and LOH; inactivation of p53 and p16INK4A) oral squamous cell carcinoma (OSCC). Fibroblasts from genetically unstable OSCC relative to the other fibroblast subtypes grew more slowly and stimulated the invasion of a non-tumourigenic keratinocyte cell line into fibroblast-rich collagen gels. To understand these findings, genome-wide transcriptional profiles were generated using the GeneChip(®) cDNA whole transcript microarray platform. Principal component analysis showed that the fibroblasts could be distinguished according to the stage of tumour development. Tumour progression was associated with down-regulation of cell cycle- and cytokinesis-related genes and up-regulation of genes encoding transmembrane proteins including cell adhesion molecules. Gene expression was validated in independent fibroblast strains using qRT-PCR. Gene connectivity and interactome-transcriptome associations were determined using a systems biology approach to interrogate the gene expression data. Clusters of gene signatures were identified that characterized genetically unstable and stable OSCCs relative to each other and to fibroblasts from normal oral mucosa. The expression of highly connected genes associated with unstable OSCCs, including those that encode α-SMA and the integrin α6, correlated with poor patient prognosis in an independent dataset of head and neck cancer. The results of this study demonstrate that fibroblasts from unstable OSCCs represent a phenotypically distinguishable subset that plays a major role in oral cancer biology. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

    2012-03-15

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac

  9. Effects of Electromagnetic Field and Basic Fibroblast Growth Factor on Osteoblast's Growth

    Institute of Scientific and Technical Information of China (English)

    GUOYong; ZHANGXi-zheng; WANGHao; LIBin; LIRui-xin; WUJin-hui; ZHAOYun-shan; WUJi-min

    2004-01-01

    Osteoblasts of rat cultured in vitro were stimulated with pulsed 50 Hz electromagnetic field and basic fibroblast growth factor(bFGF). The MTT method, flow cytometry and histochemistry staining were used to detect cell proliferation, cell cycle and alkaline phosphatase. The results indicated : after stimulated by 1 mT electromagnetic field, the cells are more abundant,have more S phase percentages, 2 mT electromagnetic field have no evident effect on cells' growth;compared with electromagnetic field, the cells stimulated by bFGF are more abundant and have larger S phase ratios. Electromagnetic field and bFGF have no effect on cells, alkaline phosphatase. Therefore ,we concluded that electromagnetic field can enhance osteoblasts growth like some growth factor such as basic fibroblast growth factor, and the osteoblasts', characteristics was not changed.

  10. Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Youichi Higuchi

    Full Text Available Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body.Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs and the subperitoneal layer (subperitoneal fibroblasts: SPFs. Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup.In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

  11. Profiling of anti-fibrotic signaling by hepatocyte growth factor in renal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Schievenbusch, Stephanie; Strack, Ingo; Scheffler, Melanie; Wennhold, Kerstin; Maurer, Julia [Institute for Pathology, University Hospital Cologne, Kerpener Str. 62, 50924 Koeln (Germany); Nischt, Roswitha [Department of Dermatology, University Hospital of Cologne (Germany); Dienes, Hans Peter [Institute for Pathology, University Hospital Cologne, Kerpener Str. 62, 50924 Koeln (Germany); Odenthal, Margarete, E-mail: m.odenthal@uni-koeln.de [Institute for Pathology, University Hospital Cologne, Kerpener Str. 62, 50924 Koeln (Germany)

    2009-07-17

    Hepatocyte growth factor (HGF) is a multifunctional growth factor affecting cell proliferation and differentiation. Due to its mitogenic potential, HGF plays an important role in tubular repair and regeneration after acute renal injury. However, recent reports have shown that HGF also acts as an anti-inflammatory and anti-fibrotic factor, affecting various cell types such as renal fibroblasts and triggering tubulointerstitial fibrosis of the kidney. The present study provides evidence that HGF stimulation of renal fibroblasts results in the activation of both the Erk1/2 and the Akt pathways. As previously shown, Erk1/2 phosphorylation results in Smad-linker phosphorylation, thereby antagonizing cellular signals induced by TGF{beta}. By siRNA mediated silencing of the Erk1/2-Smad linkage, however, we now demonstrate that Akt signaling acts as an auxiliary pathway responsible for the anti-fibrotic effects of HGF. In order to define the anti-fibrotic function of HGF we performed comprehensive expression profiling of HGF-stimulated renal fibroblasts by microarray hybridization. Functional cluster analyses and quantitative PCR assays indicate that the HGF-stimulated pathways transfer the anti-fibrotic effects in renal interstitial fibroblasts by reducing expression of extracellular matrix proteins, various chemokines, and members of the CCN family.

  12. Abnormal Uterine Bleeding: American College of Nurse-Midwives.

    Science.gov (United States)

    2016-07-01

    Variations in uterine bleeding, termed abnormal uterine bleeding, occur commonly among women and often are physiologic in nature with no significant consequences. However, abnormal uterine bleeding can cause significant distress to women or may signify an underlying pathologic condition. Most women experience variations in menstrual and perimenstrual bleeding in their lifetimes; therefore, the ability of the midwife to differentiate between normal and abnormal bleeding is a key diagnostic skill. A comprehensive history and use of the PALM-COEIN classification system will provide clear guidelines for clinical management, evidence-based treatment, and an individualized plan of care. The purpose of this Clinical Bulletin is to define and describe classifications of abnormal uterine bleeding, review updated terminology, and identify methods of assessment and treatment using a woman-centered approach.

  13. Case report: Malignant teratoma of the uterine corpus

    Directory of Open Access Journals (Sweden)

    Christmas Timothy

    2009-06-01

    Full Text Available Abstract Background Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix. Case Presentation We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection. Conclusion In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.

  14. Doppler ultrasound in the assessment of suspected intra-uterine ...

    African Journals Online (AJOL)

    Ramakantb

    outlines the diagnosis of intra-uterine growth restriction and describes how to differentiate this group ... prevalence of syndrome X, a condition associating ... low fetal hemoglobin concentration (anemic ..... such an approach remain, however.

  15. Uterine rupture an obstetrics catastrophy; incidence, risk factors ...

    African Journals Online (AJOL)

    Uterine rupture an obstetrics catastrophy; incidence, risk factors, management ... at Abubakar Tafawa Balewa University Teaching Hospital Bauchi Nigeria. ... is 0.35% and the common risk factors include high parity, exposure to oxytocin in ...

  16. Uterine prolapse complicated with a giant cervical polyp.

    Science.gov (United States)

    Massinde, Anthony Naju; Mpogoro, Filbert; Rumanyika, Richard Nyerere; Magoma, Moke

    2012-01-01

    Uterine prolapse with giant cervical polyp is a rare combination. Although uterine prolapse is common among elderly and menopausal women, giant cervical polyps are commonly encountered in young reproductive-age adults. A 55-year-old, para 7, Tanzanian woman, 7 months postmenopausal, presented with history of a protruding vaginal mass for 3 months. She also had a third-degree uterine prolapse with the cervix beyond the hymen and a huge, ulcerated, round mass on the anterior lip of the cervix. The mass had a large stalk, bled easily on touch, and measured approximately 6 × 6 cm in its largest diameter. The external cervical os and posterior cervical lip were identified and appeared normal. Transvaginal hysterectomy was performed with unremarkable recovery. Giant cervical polyp associated with uterine prolapse, although rare, can occur in menopausal women. Transvaginal hysterectomy as was done in this patient may be all that is required in benign polyps.

  17. Uterine didelphys coexisting with term pregnancy, an incidental ...

    African Journals Online (AJOL)

    Uterine didelphys coexisting with term pregnancy, an incidental finding during an ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... carry their pregnancies to term with live deliveries without any complication, some ...

  18. Misdiagnosed Uterine Rupture of an Advanced Cornual Pregnancy

    Directory of Open Access Journals (Sweden)

    Christian Linus Hastrup Sant

    2012-01-01

    Full Text Available Cornual pregnancy is a diagnostic and therapeutic challenge with potential severe consequences if uterine rupture occurs with following massive intraabdominal bleeding. We report a case of a misdiagnosed ruptured cornual pregnancy occurring at 21 weeks of gestation. Ultrasound examination and computer tomography revealed no sign of abnormal pregnancy. The correct diagnosis was first made at emergency laparotomy. Uterine rupture should be considered in pregnant women presenting with abdominal pain and haemodynamic instability.

  19. Misdiagnosed uterine rupture of an advanced cornual pregnancy

    DEFF Research Database (Denmark)

    Sant, Christian Linus Hastrup; Andersen, Poul Erik

    2012-01-01

    Cornual pregnancy is a diagnostic and therapeutic challenge with potential severe consequences if uterine rupture occurs with following massive intraabdominal bleeding. We report a case of a misdiagnosed ruptured cornual pregnancy occurring at 21 weeks of gestation. Ultrasound examination...... and computer tomography revealed no sign of abnormal pregnancy. The correct diagnosis was first made at emergency laparotomy. Uterine rupture should be considered in pregnant women presenting with abdominal pain and haemodynamic instability....

  20. Abnormal uterine bleeding in reproductive-aged women.

    Science.gov (United States)

    Matthews, Michelle L

    2015-03-01

    Abnormal uterine bleeding is a common medical condition with several causes. The International Federation of Gynecology and Obstetrics published guidelines in 2011 to develop universally accepted nomenclature and a classification system. In addition, the American College of Obstetrics and Gynecology recently updated recommendations on evaluation of abnormal uterine bleeding and indications for endometrial biopsies. This article reviews both medical and surgical treatments, including meta-analysis reviews of the most effective treatment options.

  1. Acute lymphoblastic leukemia presenting with a uterine cervical mass

    Directory of Open Access Journals (Sweden)

    N Geetha

    2015-01-01

    Full Text Available Involvement of female genital tract with acute lymphoblastic leukemia (ALL is extremely rare, and it is even rarer for a patient to have symptomatic presentation. We report the case of a middle-aged lady with ALL, who presented with severe abnormal uterine bleeding and a uterine cervical mass. Biopsy of the cervical mass showed infiltration by leukemic blasts. She received chemotherapy with Berlin-Frankfurt-Munster protocol and is alive in remission after 10 years.

  2. Recording of uterine activity from the abdominal lead EMG

    OpenAIRE

    1980-01-01

    With external tocography some form of pressure or force transducer is fastened to the abdominal wall by means of an elastic belt. Uterine contractions produce changes in the displacement of a sensor pin which acts on the transducer, producing an electrical signal that corresponds to the relative uterine pressure. External tocography, however, has the drawback that it is subject to many factors which may influence the results of the measurement. We feel that the limitations of tocography canno...

  3. Control of Postpartum Hemorrhage Using Vacuum-Induced Uterine Tamponade.

    OpenAIRE

    Purwosunu, Y; Sarkoen, W; Arulkumaran, S; Segnitz, J

    2016-01-01

    BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality worldwide. Vacuum-induced uterine tamponade is a possible alternative approach to balloon tamponade systems for the treatment of postpartum hemorrhage resulting from atony. METHOD: In a prospective proof-of-concept investigation of 10 women with vaginal deliveries in a hospital setting who failed first-line therapies for postpartum hemorrhage, tamponade was used. Vacuum-induced uterine tamponade was created through a...

  4. Hemoperitoneum Secondary to Arterial Rupture of Subserosal Uterine Leiomyoma

    Directory of Open Access Journals (Sweden)

    Pankaj Aggarwal

    2017-09-01

    Full Text Available Uterine leiomyomatas (ULs affect up to 80% of women during their reproductive years. Though relatively benign, they can have life-threatening complications. This case report presents a 50-year-old, postmenopausal female who presented with severe abdominal pain secondary to massive hemoperitoneum. Upon exploratory laparotomy, a large, pulsing artery was seen on the uterus, consistent with a ruptured subserosal uterine fibroid. This case offers unique insight into the presentation and management of this surgical emergency.

  5. Evaluation of tubal patency and uterine cavity by sonohysterography

    OpenAIRE

    Mahbod Ebrahimi

    2013-01-01

    Background Sonohysterography refers to a procedure in which fluid is instilled into uterine cavity transcervically during trans-vaginal ultrasound examination to visualize uterine cavity and tubal patency. This procedure is unknown for the most researchers and physicians in our country. Material and Methods: We collected the valid articles about sonohysterography in literatures in the last decade (2000-2012). We searched in Google scholar, Pub med, OVID, MEDLINE, EMBAS, Cochrane Labrary, SID,...

  6. Uterine cancer in the writings of Byzantine physicians.

    Science.gov (United States)

    Karamanou, Marianna; Tsoucalas, Gregory; Laios, Konstantinos; Deligeoroglou, Efthimios; Agapitos, Emmanouil; Androutsos, George

    2015-01-01

    Byzantine physicians recognized uterine cancer as a distinct disease and tried to suggest a therapeutic approach. The work of Oribasius, Aetius of Amida, Paul of Aegina, Cleopatra Metrodora and Theophanes Nonnus reflects the Hippocratic-Galenic scientific ideas as well as their own concept on this malignancy. According to their writings uterine cancer was considered an incurable disease and its treatment was based mainly on palliative herbal drugs.

  7. Factors associated with uterine endometrial hyperplasia and pyometra in wild canids: implications for fertility.

    Science.gov (United States)

    Asa, Cheryl S; Bauman, Karen L; Devery, Sarah; Zordan, Martín; Camilo, Gerardo R; Boutelle, Sally; Moresco, Anneke

    2014-01-01

    The ability to safely and effectively manage reproduction is central to the success of AZA captive-breeding programs. Although the AZA Wildlife Contraception Center routinely monitors contraceptive safety, there have been no studies that compare the effects of contraceptive use to separation of males from females, the other option for preventing reproduction. We used retrospective medical records and pathology reports submitted by AZA and related facilities for the seven AZA-managed canid species to assess rates of uterine pathology relative to female reproductive life histories. Our results showed that the prevalence of both pyometra and endometrial hyperplasia (EH) was associated not only with treatment with the two most common contraceptives (Suprelorin® and MGA implants) but also with the number of years barren (i.e., not producing a litter and not contracepted). Rates of pyometra and EH were especially high in African painted dogs and red wolves, but lowest in swift and fennec foxes. The number of years producing a litter had a low association, suggesting it could be protective against uterine pathology. A more recently developed Suprelorin® protocol using Ovaban® to prevent the initial stimulation phase, followed by implant removal when reversal is desired, may be a safer contraceptive option. These results concerning the relationship between reproductive management and uterine health have important implications for AZA-managed programs, since the unsustainability of many captive populations may be due at least in part to infertility. Managing a female's reproductive lifespan to optimize or maintain fertility will require a reconsideration of how breeding recommendations are formulated. © 2013 Wiley Periodicals, Inc.

  8. The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation.

    Science.gov (United States)

    Lefkowitz, Ariel; Edwards, Marcel; Balayla, Jacques

    2012-04-01

    Absolute uterine factor infertility (UFI) refers to the refractory causes of female infertility stemming from the anatomical or physiological inability of a uterus to sustain gestation. Today, uterine factor infertility affects 3-5% of the population. Traditionally, although surrogacy and adoption have been the only viable options for females affected by this condition, the uterine transplant is currently under investigation as a potential medical alternative for women who desire to go through the experience of pregnancy. Although animal models have shown promising results, human transplantation cases have only been described in case reports and a successful transplant leading to gestation is yet to occur in humans. Notwithstanding the intricate medical and scientific complexities that a uterine transplant places on the medical minds of our time, ethical questions on this matter pose a similar, if not greater, challenge. In light of these facts, this article attempts to present the ethical issues in the context of experimentation and standard practice which surround this controversial and potentially paradigm-altering procedure; and given these, introduces "The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation", a set of proposed criteria required for a woman to be ethically considered a candidate for uterine transplantation.

  9. Measurement of phenolic environmental estrogens in women with uterine leiomyoma.

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    Yang Shen

    Full Text Available OBJECTIVES: To investigate the effect of phenolic environmental estrogens on uterine leiomyoma from the perspective of clinical epidemiology. METHODS: Urine and blood samples were collected from Han women with uterine leiomyoma and women without uterine leiomyoma, living in Nanjing, China, between September 2011 and February 2013. A total of 156 urine samples and 214 blood samples were collected from the uterine leiomyoma group and 106 urine samples and 126 blood plasma samples from the control group. Bisphenol A (BPA, nonylphenol (NP and octylphenol (OP concentrations were determined by solid-phase extraction (SPE coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS. RESULTS: Phenolic environmental estrogens in the uterine leiomyoma and control groups were compared based on: gravida>3 and gravida ≤ 3. In participants with gravida>3, urine OP concentration was significantly (P0.05 different between gravida>3 and gravida ≤ 3 patients. There was no significant (P>0.05 difference in plasma concentrations of BPA, OP and NP between the leiomyoma group and control group. Mean exposure concentration and range of distribution of BPA, OP and NP plasma concentration differed between the uterine leiomyoma and control group. CONCLUSION: Exposure level of phenolic environmental estrogens in human was related with leiomyoma tumorigenesis.

  10. Uterine ALK3 is essential during the window of implantation

    Science.gov (United States)

    Monsivais, Diana; Clementi, Caterina; Peng, Jia; Titus, Mary M.; Barrish, James P.; Creighton, Chad J.; Lydon, John P.; DeMayo, Francesco J.; Matzuk, Martin M.

    2016-01-01

    The window of implantation is defined by the inhibition of uterine epithelial proliferation, structural epithelial cell remodeling, and attenuated estrogen (E2) response. These changes occur via paracrine signaling between the uterine epithelium and stroma. Because implantation defects are a major cause of infertility in women, identifying these signaling pathways will improve infertility interventions. Bone morphogenetic proteins (BMPs) are TGF-β family members that regulate the postimplantation and midgestation stages of pregnancy. In this study, we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. Conditional knockout (cKO) of ALK3 in the uterus was obtained by producing Alk3flox/flox-Pgr-cre–positive females. Alk3 cKO mice are sterile and have defects in the luminal uterine epithelium, including increased microvilli density and maintenance of apical cell polarity. Moreover, Alk3 cKO mice exhibit an elevated uterine E2 response and unopposed epithelial cell proliferation during the window of implantation. We determined that dual transcriptional regulation of Kruppel-like factor 15 (Klf15), by both the transforming growth factor β (TGF-β) transcription factor SMAD family member 4 (SMAD4) and progesterone receptor (PR), is necessary to inhibit uterine epithelial cell proliferation, a key step for embryo implantation. Our findings present a convergence of BMP and steroid hormone signaling pathways in the regulation of uterine receptivity. PMID:26721398

  11. Ayurvedic management of recurrent abortions due to uterine fibroid

    Directory of Open Access Journals (Sweden)

    Shailendra Dadarao Katakdound

    2017-01-01

    Full Text Available Uterine fibroids are present in 30-70% of women of reproductive age. Uterine fibroids distort the uterine cavity. Therefore there is consensus of a negative impact on both the clinical pregnancy and delivery rates.[2] In addition, studies have also reported an increased risk of spontaneous miscarriage with submucosal fibroids. In biomedicine, myomectomy is considered the treatment of choice and Assisted Reproductive Technology is advised to overcome infertility. In Hārita Saṃhitā treatment is given for recurrent abortion (Garbhasrāvī. In this study, considering pitta doṣa and altered uterine receptivity (kṣetra duṣṭi as causative factors, purgation (virecana karma was done, enema (yoga basti was given after post purgation protocol (saṃsarjana karma. After body purification (śodhana, garbhasthāpaka drugs were given to the patient for one month. Patient conceived in the second month with this treatment. In Antenatal Care, haematinics and calcium supplements and month wise Ayurvedic medication (Māsānumāsika kaṣāya were given for nine months. Elective caesarean section as done after GA 38 weeks (USG followed by inj. Wymesone 8 mg. The procedure uneventful. Thus proving Ayurvedic management of recurrent abortion due to uterine fibroid. It is cost effective and improves and normalises uterine receptive environment.

  12. Uterine ALK3 is essential during the window of implantation.

    Science.gov (United States)

    Monsivais, Diana; Clementi, Caterina; Peng, Jia; Titus, Mary M; Barrish, James P; Creighton, Chad J; Lydon, John P; DeMayo, Francesco J; Matzuk, Martin M

    2016-01-19

    The window of implantation is defined by the inhibition of uterine epithelial proliferation, structural epithelial cell remodeling, and attenuated estrogen (E2) response. These changes occur via paracrine signaling between the uterine epithelium and stroma. Because implantation defects are a major cause of infertility in women, identifying these signaling pathways will improve infertility interventions. Bone morphogenetic proteins (BMPs) are TGF-β family members that regulate the postimplantation and midgestation stages of pregnancy. In this study, we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. Conditional knockout (cKO) of ALK3 in the uterus was obtained by producing Alk3(flox) (/flox)-Pgr-cre-positive females. Alk3 cKO mice are sterile and have defects in the luminal uterine epithelium, including increased microvilli density and maintenance of apical cell polarity. Moreover, Alk3 cKO mice exhibit an elevated uterine E2 response and unopposed epithelial cell proliferation during the window of implantation. We determined that dual transcriptional regulation of Kruppel-like factor 15 (Klf15), by both the transforming growth factor β (TGF-β) transcription factor SMAD family member 4 (SMAD4) and progesterone receptor (PR), is necessary to inhibit uterine epithelial cell proliferation, a key step for embryo implantation. Our findings present a convergence of BMP and steroid hormone signaling pathways in the regulation of uterine receptivity.

  13. DIAGNOSTIC IMPLICATIONS OF IMMUNOHISTOCHEMICAL MARKERS IN UTERINE SMOOTH MUSCLE TUMORS

    Institute of Scientific and Technical Information of China (English)

    朱雪琼; 石一复; 陈晓端; 吴裕中

    2004-01-01

    Objective: To evaluate the diagnostic implications of immunohistochemical markers in uterine smooth muscle tumors. Methods: Formalin-fixed paraffin-embedded tissue blocks were selected from 17 uterine leiomyosarcomas, 40 uterine unusual leiomyomas and 25 uterine usual leiomyomas. Utilizing immunohistochemical techniques with antigen retrieval, serial sections of each tumor for immunoreactivity with myogenic markers, ovarian steroid receptors, CD44v3, proliferating cell nuclear antigen and mast cells were assessed. Results: Although the myogenic markers and CD44v3 showed less frequent positivity in uterine leiomyosarcomas than those in unusual leiomyomas, they were not reliable markers for differentiating leiomyosarcoma from leiomyoma. Uterine leiomyosarcoma tended to have lower ovarian steroid receptors immunoreactivity rates than leiomyoma. Leiomyoma tended to have a higher quantity of intratumoral mast cells than leiomyosarcoma, while the expression of proliferating cell nuclear antigen was lower in them. Conclusion: Because the estimation of mitotic count was subject to significant variation, the immunohistochemical expression of ovarian steroid receptors, mast cells and proliferating cell nuclear antigen seemed to be helpful for the discrimination of unusual leiomyoma from leiomyosarcoma.

  14. A rare case of uterine leiomyosarcoma: a case report

    Directory of Open Access Journals (Sweden)

    Chinamotu Rao N

    2010-07-01

    Full Text Available Abstract Introduction Malignant change in a leiomyoma or uterine fibroid is termed leiomyosarcoma. It arises from smooth muscle of the uterus and is a rare tumor that accounts for 2% to 5% of all uterine malignancies. Very few cases are reported in the literature. Our patient did not have any history of genital bleeding, which is the usual presentation in uterine sarcoma. We report an original case report of an unusual presentation of this rare tumor arising from the uterus. Case presentation A 40-year-old nulliparous woman of South Indian origin presented with a mass in her abdomen for one year with a rapid increase in size over the previous three months. Tumor marker CA-125 was raised, and a computed tomography scan showed a mass arising from the pelvis. An exploratory laparotomy was performed and the histopathology report confirmed the diagnosis of uterine leiomyosarcoma. Conclusion Because of their rarity, uterine sarcomas are not suitable for screening. Diagnosis is by histopathologic examination and surgery is the only treatment. The prognosis for women with uterine sarcoma primarily depends on the extent of disease at the time of diagnosis and the mitotic index.

  15. Control of Postpartum Hemorrhage Using Vacuum-Induced Uterine Tamponade.

    Science.gov (United States)

    Purwosunu, Yuditiya; Sarkoen, Widyastuti; Arulkumaran, Sabaratnam; Segnitz, Jan

    2016-07-01

    Postpartum hemorrhage is the leading cause of maternal mortality worldwide. Vacuum-induced uterine tamponade is a possible alternative approach to balloon tamponade systems for the treatment of postpartum hemorrhage resulting from atony. In a prospective proof-of-concept investigation of 10 women with vaginal deliveries in a hospital setting who failed first-line therapies for postpartum hemorrhage, tamponade was used. Vacuum-induced uterine tamponade was created through a device inserted transvaginally into the uterine cavity. An occlusion balloon built into the device shaft was inflated at the level of the external cervical os to create a uterine seal. Negative pressure was created by attaching a self-contained, mobile, electrically powered, pressure-regulated vacuum pump with a sterile graduated canister. In all 10 cases, the suction created an immediate seal at the cervical os, 50-250 mL of residual blood was evacuated from the uterine cavity, the uterus collapsed and regained tone within minutes, and hemorrhaging was controlled. The device remained in place for a minimum of 1 hour and up to 6.5 hours in one case while vaginal and perineal lacerations were easily repaired. This preliminary investigation suggests that a device designed to create vacuum-induced uterine tamponade may be a reasonable alternative to other devices used to treat atonic postpartum hemorrhage.

  16. The aromatase inhibitor letrozole reduces adhesion formation after intraperitoneal surgery in a rat uterine horn model.

    Science.gov (United States)

    Keskin, Huseyin Levent; Sirin, Yusuf Sinan; Keles, Hikmet; Turgut, Olcay; Ide, Tayfun; Avsar, Ayse Filiz

    2013-04-01

    To investigate, in an experimental animal study, the effects of letrozole and tamoxifen in the reduction of adhesion formation following abdominopelvic surgery. Thirty female Wistar albino rats were included and divided into three groups. One group received 500 μg/d tamoxifen and a second group received 1 mg/kg/d letrozole through an enteric tube. A third group did not receive any drugs and served as the control group. On the fifth day, a laparotomy was performed and the right uterine horn was injured by monopolar cautery. The left uterine horn was incised with a scalpel and sutured. The preventive therapy protocols were continued for 7 days after surgery. On the 14th day after first surgery the animals were sacrificed, and the intraperitoneal macroscopic adhesion formation and microscopic adhesion features were evaluated. The Kruskal-Wallis test was used to compare the scores of the macroscopic adhesion scores and histologic features among the three groups, followed by a post hoc Mann-Whitney test. The total histological score was analyzed with a one-way ANOVA, followed by post hoc Bonferroni correction tests. p values ≤0.05 were considered statistically significant. The level of significance was set at p≤0.016 for the post hoc tests. The letrozole and tamoxifen groups had significantly lower adhesion scores for the right uterine horn than the control group (p=0.005 and p=0.013, respectively). For the left horn, however, only the letrozole group had a lower macroscopic adhesion score than the controls (p=0.011). The total histological score was significantly lower in the letrozole group than in the control group (p=0.014), but no differences were found between the tamoxifen group and the control group (p=0.954). Inflammation, fibroblastic activity, collagen formation and vascular proliferation were significantly lower in the letrozole group compared with the control group (p0.05). Tamoxifen administration did not result in any significant effects on the

  17. Dermal Wound Fibroblasts and Matrix Metaloproteinases (MMPs: Their Possible Role in Allergic Contact Dermatitis

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Khorramizadeh

    2004-03-01

    signals are also altered and that ACD fibroblasts exhibit hyper-responsiveness to mitogenic or fibrogenic stimulants. Altogether, these data address the chronocity and non-healing tendency of ACD wounds. However, more studies are required to examine possible MMPs inhibition and differential expression of mytogenic, fibrogenic and antifibrogenic cytokines in ACD wound beds. In particular, MMP-2 is postulated to be an aim for further gene therapy protocols.

  18. Dermal Wound Fibroblasts and Matrix Metaloproteinases (MMPs): Their Possible Role in Allergic Contact Dermatitis.

    Science.gov (United States)

    Khorramizadeh, Mohammad Reza; Falak, Reza; Pezeshki, Mohammad; Safavifar, Farnaz; Mansouri, Parvin; Ghahary, Aziz; Saadat, Farshid; Varshokar, Kamran

    2004-03-01

    altered and that ACD fibroblasts exhibit hyper-responsiveness to mitogenic or fibrogenic stimulants. Altogether, these data address the chronocity and non-healing tendency of ACD wounds. However, more studies are required to examine possible MMPs inhibition and differential expression of mytogenic, fibrogenic and antifibrogenic cytokines in ACD wound beds. In particular, MMP-2 is postulated to be an aim for further gene therapy protocols.

  19. Elevated transforming growth factor β and mitogen-activated protein kinase pathways mediate fibrotic traits of Dupuytren's disease fibroblasts

    Directory of Open Access Journals (Sweden)

    Krause Carola

    2011-06-01

    Full Text Available Abstract Background Dupuytren's disease is a fibroproliferative disorder of the palmar fascia. The treatment used to date has mostly been surgery, but there is a high recurrence rate. Transforming growth factor β (TGF-β has been implicated as a key stimulator of myofibroblast activity and fascial contraction in Dupuytren's disease. Results We studied Dupuytren's fibroblasts in tissues ex vivo and in cells cultured in vitro and found increased TGF-β expression compared to control fibroblasts. This correlated not only with elevated expression and activation of downstream Smad effectors but also with overactive extracellular signal-regulated kinase 1/2 (ERK1/2/mitogen-activated protein (MAP kinase signalling. Treatment with the TGF-β type I receptor kinase inhibitor SB-431542 and bone morphogenetic protein 6 (BMP6 led to inhibition of elevated Smad and ERK1/2/MAP kinase signalling as well as to inhibition of the increased contractility of Dupuytren's fibroblasts. BMP6 attenuated TGF-β expression in Dupuytren's fibroblasts, but not in control fibroblasts. Platelet-derived growth factor (PDGF expression was strongly promoted by TGF-β in Dupuytren's fibroblasts and was curbed by SB-431542 or BMP6 treatment. High basal expression of phosphorylated ERK1/2 MAP kinase and fibroproliferative markers was attenuated in Dupuytren's fibroblasts by a selective PDGF receptor kinase inhibitor. Cotreatment of Dupuytren's fibroblasts with SB-431542 and the mitogen-activated protein kinase kinase 1 inhibitor PD98059 was sufficient to abrogate proliferation and contraction of Dupuytren's fibroblasts. Conclusions Both TGF-β and ERK1/2 MAP kinase pathways cooperated in mediating the enhanced proliferation and high spontaneous contraction of Dupuytren's fibroblasts. Our data indicate that both signalling pathways are prime targets for the development of nonsurgical intervention strategies to treat Dupuytren's disease.

  20. Uterine contractions evaluated on cine MR imaging in patients with uterine leiomyomas

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Mizuki E-mail: mizuki@mbox.kyoto-inet.or.jpnishinomizuki@hotmail.com; Togashi, Kaori; Nakai, Asako; Hayakawa, Katsumi; Kanao, Shotarou; Iwasaku, Kazuhiro; Fujii, Shingo

    2005-01-01

    Purpose: Submucosal leiomyoma is one of the most recognized causes of infertility and habitual abortion. The purpose of this study is to evaluate uterine peristalsis, a cycle-related inherent contractility of uterus probably responsible for sperm transport and conservation of pregnancy, in patients with uterine leiomyomas using cine magnetic resonance (MR) imaging. Materials and methods: Study population consisted of 26 female patients (age range: 19-51 years, mean: 41 years), in which 16 patients had submucosal leiomyomas and 10 patients had intramural or subserosal leiomyomas. We prospectively performed MR imaging of the midsagittal plane of uterus using 1.5 T magnet (Symphony, Siemens Medical Systems) with a body array coil, and obtained 60 half-Fourier acquisition single shot turbo spin echo (HASTE) images (Echo time=80 ms, FOV=300 mm, slice thickness 5 mm, matrix 256x256) within 2 min, and displayed them on cine mode at 12x faster than real speed. Evaluated were peristaltic movements at the endometral-myometrial junction and focal myometrial movements, adjacent to leiomyomas, regarding presence, direction, frequency, and conduction. Results: The peristaltic movements were identified in 12/16 patients with submucosal lesions and 10/10 with other leiomyomas. The frequency and direction were cycle-related. Loss of peristalsis was noted adjacent to submucosal myomas in 4/12 patients, but was not in others. Focal myometrial movements were noted in 9/16 patients with submucosal myomas, but not in others. Conclusions: Uterine peristaltic movements were partly interrupted by submucosal leiomoymas, but not by myometrial or subserosal leiomyomas. Loss of peristalsis and focal myometrial movements was noted only adjacent to submucosal leiomyomas. These findings are considered to represent dysfunctional contractility, and may be related with pregnancy loss.

  1. Uterine Artery Embolization Versus Laparoscopic Uterine Artery Occlusion: The Outcomes of a Prospective, Nonrandomized Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    Mara, Michal; Kubinova, Kristyna, E-mail: kristyna.kubinova@gmail.com [General Faculty Hospital and 1st Medical Faculty of Charles University, Department of Obstetrics and Gynecology (Czech Republic); Maskova, Jana [Aberdeen Royal Infirmary, Department of Radiology (United Kingdom); Horak, Petr [General Faculty Hospital and 1st Medical Faculty of Charles University, Department of Obstetrics and Gynecology (Czech Republic); Belsan, Tomas [Central Military Hospital, Department of Radiology (Czech Republic); Kuzel, David [General Faculty Hospital and 1st Medical Faculty of Charles University, Department of Obstetrics and Gynecology (Czech Republic)

    2012-10-15

    Purpose: To compare outcomes of two different types of occlusive therapy of uterine fibroids. Methods: Women with fibroid(s) unsuitable for laparoscopic myomectomy (LM) were treated with uterine artery embolization (UAE) or laparoscopic uterine artery occlusion (LUAO). Results: Before the procedure, patients treated with UAE (n = 100) had a dominant fibroid greater in size (68 vs. 48 mm) and a mean age lower (33.1 vs. 34.9 years) than surgically treated patients (n = 100). After 6 months, mean shrinkage of fibroid volume was 53 % after UAE and 39 % after LUAO (p = 0.063); 82 % of women after UAE, but only 23 % after LUAO, had complete myoma infarction (p = 0.001). Women treated with UAE had more complications (31 vs. 11 cases, p = 0.006) and greater incidence of hysteroscopically verified intrauterine necrosis (31 vs. 3 %, p = 0.001). Both groups were comparable in markers of ovarian functions and number of nonelective reinterventions. The groups did not differ in pregnancy (69 % after UAE vs. 67 % after LUAO), delivery (50 vs. 46 %), or abortion (34 vs. 33 %) rates. The mean birth weight of neonates was greater (3270 vs. 2768 g, p = 0.013) and the incidence of intrauterine growth restriction lower (13 vs. 38 %, p = 0.046) in post-UAE patients. Conclusion: Both methods are effective in the treatment of women with future reproductive plans and fibroids not suitable for LM. UAE is more effective in causing complete ischemia of fibroids, but it is associated with greater risk of intrauterine necrosis. Both methods have low rate of serious complications (except for a high abortion rate).

  2. Chaperonin containing T-complex polypeptide subunit eta (CCT-eta is a specific regulator of fibroblast motility and contractility.

    Directory of Open Access Journals (Sweden)

    Latha Satish

    Full Text Available Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta is specifically reduced in healing fetal wounds in a rabbit model. In this study, we examine the role of CCT-eta in fibroblast motility and contractility, properties essential to wound healing and scar formation. We demonstrate that CCT-eta (but not CCT-beta is underexpressed in fetal fibroblasts compared to adult fibroblasts. An in vitro wound healing assay demonstrated that adult fibroblasts showed increased cell migration in response to epidermal growth factor (EGF and platelet derived growth factor (PDGF stimulation, whereas fetal fibroblasts were unresponsive. Downregulation of CCT-eta in adult fibroblasts with short inhibitory RNA (siRNA reduced cellular motility, both basal and growth factor-induced; in contrast, siRNA against CCT-beta had no such effect. Adult fibroblasts were more inherently contractile than fetal fibroblasts by cellular traction force microscopy; this contractility was increased by treatment with EGF and PDGF. CCT-eta siRNA inhibited the PDGF-induction of adult fibroblast contractility, whereas CCT-beta siRNA had no such effect. In each of these instances, the effect of downregulating CCT-eta was to modulate the behavior of adult fibroblasts so as to more closely approximate the characteristics of fetal fibroblasts. We next examined the effect of CCT-eta modulation on alpha-smooth muscle actin (alpha-SMA expression, a gene product well known to play a critical role in adult wound healing. Fetal fibroblasts were found to constitutively express less alpha-SMA than adult cells. Reduction of CCT-eta with siRNA had minimal effect on cellular

  3. Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts.

    Science.gov (United States)

    Lu, Jiamei; Zhu, Yanting; Feng, Wei; Pan, Yilin; Li, Shaojun; Han, Dong; Liu, Lu; Xie, Xinming; Wang, Guizuo; Li, Manxiang

    2014-09-01

    Interleukin-13 (IL-13) is associated with the production of collagen in airway remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction of collagen remain unclear; the aim of this study is to address this issue. IL-13 dose- and time-dependently-induced collagen I production in primary cultured airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre-treatment of cells with JAK inhibitor suppressed IL-13- induced collagen I production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and the presence of either PDGF receptor blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts.

  4. Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts

    Indian Academy of Sciences (India)

    Jiamei Lu; Yanting Zhu; Wei Feng; Yilin Pan; Shaojun Li; Dong Han; Lu Liu; Xinming Xie; Guizuo Wang; Manxiang Li

    2014-09-01

    Interleukin-13 (IL-13) is associated with the production of collagen in airway remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction of collagen remain unclear; the aim of this study is to address this issue. IL-13 dose- and time-dependently-induced collagen I production in primary cultured airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre-treatment of cells with JAK inhibitor suppressed IL-13-induced collagen I production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and the presence of either PDGF receptor blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts.

  5. Matrine inhibits proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB

    Institute of Scientific and Technical Information of China (English)

    WU Yan-an; GAO Chun-fang; WANG Hao; HUANG Chao; KONG Xian-tao

    2001-01-01

    To study the effect of matrine on proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB (PDGF-BB). Methods: Mouse skin fibroblasts were obtained from newborn ⅠCR mice and propagated in vitro. Proliferation of cell was analyzed by mitochondrial reduction of tetrazolium salt MTT and actual cell count. Results: Matrine (50 to 500 μg/ml) caused dose-dependent reduction of serum-stimulated cell growth. Growth inhibition was totally reversed after removal of the drug. Matrine also inhibited PDGF-BB induced cell growth dose-dependently. Conclusion: Matrine exhibits potent anti-proliferation effect on mouse skin fibroblast. This effect appears to be mediated by decrease of PDGF-induced growth. These results suggest that matrine might have preventive and therapeutic implication in skin fibrosis.

  6. [Risk of uterine rupture in vaginal birth after cesarean: Systematic review].

    Science.gov (United States)

    Hidalgo-Lopezosa, Pedro; Hidalgo-Maestre, María

    To assess the risk of uterine rupture (UR) in attempted vaginal birth after cesarean and to identify risk factors. Systematic review by consulting the following databases: PubMed (MEDLINE), Cochrane Library Plus, Embase, Nursing@Ovid, Cuidatge and Dialnet. The search was conducted between January and March 2015. MeSH descriptors used were: vaginal birth after cesarean; uterine rupture; labor induced and labor obstetric or trial of labor. There were no restrictions on date or language. The selection of articles was performed by 2 independent reviewers, standardized and unblinded. A critical review of the summary was conducted, and if was necessary, the full text was consulted. Prospective and retrospective documents were included. A total of 39 documents were included for their relevance and interest. Few clinical trials were found. The UR incidence on the results of the studies analyzed ranged from 0.15-0.98% in spontaneous labor; 0.3-1.5% in stimulation and induction with oxytocin, and 0.68-2.3% in prostaglandin inductions. The success of vaginal birth after cesarean is important and improves when conditions are optimal. However it is not without risks, the main one being UR. Induction of labor with oxytocin and/or prostaglandins appears as the main risk factor, while the spontaneous onset of labor and a prior vaginal birth are protective factors. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma.

    Science.gov (United States)

    Fuchigami, Takao; Kibe, Toshiro; Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio; Nishizawa, Yoshiaki; Hijioka, Hiroshi; Fujii, Tomomi; Ueda, Masahiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Michiko

    2014-09-05

    Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium.

    Science.gov (United States)

    Hur, Woojune; Lee, Hoon Young; Min, Hye Sook; Wufuer, Maierdanjiang; Lee, Chang-Won; Hur, Ji An; Kim, Sang Hyon; Kim, Byeung Kyu; Choi, Tae Hyun

    2017-04-20

    Fibroblasts are ubiquitous cells in the human body and are absolutely necessary for wound healing such as for injured skin. This role of fibroblasts was the reason why we aimed to differentiate human adipose-derived stem cells (hADSCs) into fibroblasts and to test their wound healing potency. Recent reports on hADSC-derived conditioned medium have indicated stimulation of collagen synthesis as well as migration of dermal fibroblasts in wound sites with these cells. Similarly, human fibroblast-derived conditioned medium (F-CM) was reported to contain a variety of factors known to be important for growth of skin. However, it remains unknown whether and how F-CM can stimulate hADSCs to secrete type I collagen. In this study, we obtained F-CM from the culture of human skin fibroblast HS27 cells in DMEM media. For an in-vivo wound healing assay using cell transplantation, balb/c nude mice with full-thickness skin wound were used. Our data showed that levels of type I pro-collagen secreted by hADSCs cultured in F-CM increased significantly compared with hADSCs kept in normal medium for 72 h. In addition, from a Sircol collagen assay, the amount of collagen in F-CM-treated hADSC conditioned media (72 h) was markedly higher than both the normal medium-treated hADSC conditioned media (72 h) and the F-CM (24 h). We aimed to confirm that hADSCs in F-CM would differentiate into fibroblast cells in order to stimulate wound healing in a skin defect model. To investigate whether F-CM induced hADSCs into fibroblast-like cells, we performed FACS analysis and verified that both F-CM-treated hADSCs and HS27 cells contained similar expression patterns for CD13, CD54, and CD105, whereas normal medium-treated hADSCs were significantly different. mRNA level  analysis for Nanog, Oct4A, and Sox2 as undifferentiation markers and vimentin, HSP47, and desmin as matured fibroblast markers supported the characterization that hADSCs in F-CM were highly differentiated into fibroblast

  9. The effects of Arcanobacterium pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo.

    Science.gov (United States)

    Miller, A N A; Williams, E J; Sibley, K; Herath, S; Lane, E A; Fishwick, J; Nash, D M; Rycroft, A N; Dobson, H; Bryant, C E; Sheldon, I M

    2007-10-15

    Uterine bacterial infection after parturition causes endometritis, perturbs ovarian function and leads to infertility in cattle. Although endometritis is caused by mixed infections, endometrial pathology is associated with the presence of Arcanobacterium pyogenes. The aims of the present study were to determine the effects of A. pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo. Heat-killed A. pyogenes did not affect the production of prostaglandin F2alpha (PGF) or prostaglandin E(2) (PGE) from endometrial explants, or purified populations of endometrial epithelial or stromal cells. However, the explants produced more PGF and PGE than controls when treated with a bacteria-free filtrate (BFF) cultured from A. pyogenes. Similarly, BFF stimulated PGF and PGE production by epithelial and stromal cells, respectively. So, BFF or control PBS was infused into the uterus of heifers (n=7 per group) for 8 days, starting the day after estrus. Emergence of the follicle wave, dominant follicle or corpus luteum diameter, and peripheral plasma FSH, LH, estradiol, progesterone, PGFM, or acute phase protein concentrations were unaffected by the BFF infusion. In the live animal it is likely that the intact uterine mucosa limits the exposure of the endometrial cells to the exotoxin of A. pyogenes, whereas the cells are readily exposed to the toxin in vitro.

  10. Evidence for estrogen-dependent uterine serpin (SERPINA14) expression during estrus in the bovine endometrial glandular epithelium and lumen.

    Science.gov (United States)

    Ulbrich, Susanne E; Frohlich, Thomas; Schulke, Katy; Englberger, Eva; Waldschmitt, Nadine; Arnold, Georg J; Reichenbach, Horst-Dieter; Reichenbach, Myriam; Wolf, Eckhard; Meyer, Heinrich H D; Bauersachs, Stefan

    2009-10-01

    Uterine secretions have a dominant impact on the environment in which embryo development takes place. The uterine serpins (SERPINA14, previously known as UTMP) are found most abundantly during pregnancy in the uterus of ruminants. Although progesterone is currently assumed to be the major regulator of SERPINA14 expression, our recent study of transcriptome changes in bovine endometrium during the estrous cycle unexpectedly detected a marked upregulation of SERPINA14 mRNA levels at estrus. The present study describes the full-length mRNA sequence, genomic organization, and putative promoter elements of the SERPINA14 gene. The SERPINA14 mRNA abundance was quantified by real-time RT-PCR in intercaruncular endometrium at several time points during the estrous cycle and early pregnancy. Highest levels were found at estrus, followed by a dramatic decrease and a moderate expression during the luteal phase. Transcript levels were higher in pregnant endometrium compared with controls at Day 18. At estrus, immunoreactive protein was localized in deep glandular epithelium, and Western blotting concomitantly showed the 52-kDa form in uterine flushings. SERPINA14 mRNA was significantly upregulated in glandular endometrial cells in vitro after stimulation with estradiol-17beta and progesterone, but not after interferon-tau treatment. Our results clearly demonstrate that SERPINA14 appears distinctly in bovine endometrium during the estrus phase. A supporting role toward providing a well-prepared endometrial environment for passing gametes, especially sperm, is assumed.

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

    Science.gov (United States)

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

    2011-08-01

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

  12. [Intra-uterine device and nulliparous women].

    Science.gov (United States)

    Trignol-Viguier, N; Blin, E; Marret, H

    2014-06-01

    Intra-uterine device (IUD) is one of the birth control methods, which is available for nulliparous women, even though misconceptions still remain in medical or popular opinion. Only 1.3 % of nulliparous have a IUD as contraception in France while it is the second methods used by all women, after pill. The best contraception is the one chosen by women; however, the choice for a nulliparous of an IUD may be really difficult, despite the increasing number of women wishing to use it. Long-acting reversible contraceptives utilization, including IUD, is probably one of the issues to decrease the unintended pregnancies. An exhaustive and clear information about IUD is necessary to allow an informed and real choice. This prescription must consider contraindications and medical conditions for safe insertion, especially to avoid infection by screening STD (Chlamydia trachomatis and Nesseria gonorrhoeae) in nulliparous womenIUD preferred. Even if side effects such as expulsion, pelvic pains or dysmenorrhea are more frequent by nulliparous, IUD is a first intention choice for contraception to be consider, that women could obtain easily, including in emergency contraception situation.

  13. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women.

    Science.gov (United States)

    Wolf, Myles; Koch, Todd A; Bregman, David B

    2013-08-01

    Fibroblast growth factor 23 (FGF23) is an osteocyte-derived hormone that regulates phosphate and vitamin D homeostasis. Through unknown mechanisms, certain intravenous iron preparations induce acute, reversible increases in circulating FGF23 levels that lower serum phosphate in association with inappropriately low levels of calcitriol, similar to genetic diseases of primary FGF23 excess. In contrast, studies in wild-type mice suggest that iron deficiency stimulates fgf23 transcription but does not result in hypophosphatemia because FGF23 is cleaved within osteocytes by an unknown catabolic system. We tested the association of iron deficiency anemia with C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 55 women with a history of heavy uterine bleeding, and assessed the longitudinal biochemical response over 35 days to equivalent doses of randomly-assigned, intravenous elemental iron in the form of ferric carboxymaltose (FCM) or iron dextran. Iron deficiency was associated with markedly elevated cFGF23 (807.8 ± 123.9 relative units [RU]/mL) but normal iFGF23 (28.5 ± 1.1 pg/mL) levels at baseline. Within 24 hours of iron administration, cFGF23 levels fell by approximately 80% in both groups. In contrast, iFGF23 transiently increased in the FCM group alone, and was followed by a transient, asymptomatic reduction in serum phosphate iron dextran group. Reduced serum phosphate was accompanied by increased urinary fractional excretion of phosphate, decreased calcitriol levels, and increased parathyroid hormone levels. These findings suggest that iron deficiency increases cFGF23 levels, and that certain iron preparations temporarily increase iFGF23 levels. We propose that intravenous iron lowers cFGF23 in humans by reducing fgf23 transcription as it does in mice, whereas carbohydrate moieties in certain iron preparations may simultaneously inhibit FGF23 degradation in osteocytes leading to transient increases in iFGF23 and reduced serum phosphate.

  14. Obstetric outcome of women with uterine anomalies in China

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan; ZHAO Yang-yu; QIAO Jie

    2010-01-01

    Background Congenital uterine anomalies are associated with the highest incidence of reproductive failure and obstetric complications. This study aimed to summarize the clinical characteristics and prenatal outcome of pregnancy in women with congenital uterine malformations.Methods This retrospective study evaluated the fertility and obstetric outcome of 116 inpatients with uterine malformations with pregnancy in Peking University Third Hospital from June 1998 to June 2009. A total of 270 randomly selected pregnant women with a previously confirmed normally shaped uterus as a control group. Student's t test and analysis of variance (ANOVA) were used to compare means for normally distributed variables. The analysis was carried out using the SPSS.Results Among 21 961 deliveries in Peking University Third Hospital, 116 (0.45%) were in women with uterine anomalies. A septate uterus was present in 43 (37.1%) and the uterus didelphys in 28 (24.2%) of the 116 women identified. Bicornuate uterus, arcuate and unicomate uterus were observed in 12 (10.3%), 18 (15.5%) and 15 (12.9%) patients, respectively. Patients with uterine anomalies had significantly higher rates of malpresentation (38.8%), preterm delivery (19.8%), and cesarean section (78.5%) compared with the group of women with a normal uterus. Patients with uterine anomalies had significantly lower mean birth-weight neonates and a significantly higher incidence of small for gestationalage (SGA) neonates; women with uterus didelphys more frequently required infertility treatment than patients with other uterine anomalies (P <0.001). The rate of malpresentation was significantly higher in patients with septated uterus in comparison with patients with uterus unicorns (P <0.05).Conclusions Women with congenital uterinemal formation usually have higher incidence of complications during pregnancy and delivery. A septate uterus appears to be associated with poorer obstetric outcomes.

  15. Human uterine wall tension trajectories and the onset of parturition.

    Directory of Open Access Journals (Sweden)

    Peter Sokolowski

    Full Text Available Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000-2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased P < 0.05 compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (P < 0.001, but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension.

  16. Human uterine wall tension trajectories and the onset of parturition.

    Science.gov (United States)

    Sokolowski, Peter; Saison, Francis; Giles, Warwick; McGrath, Shaun; Smith, David; Smith, Julia; Smith, Roger

    2010-06-23

    Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000-2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased P < 0.05 compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (P < 0.001), but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension.

  17. Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch.

    Science.gov (United States)

    Dicker, Anthony J; Serewko, Magdalena M; Russell, Terry; Rothnagel, Joseph A; Strutton, Geoff M; Dahler, Alison L; Saunders, Nicholas A

    2002-05-01

    In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).

  18. The Role of Human Adult Peripheral and Umbilical Cord Blood Platelet-Rich Plasma on Proliferation and Migration of Human Skin Fibroblasts.

    Science.gov (United States)

    Hashemi, Seyedeh-Sara; Mahmoodi, Mahdokht; Rafati, Ali Reza; Manafi, Farzad; Mehrabani, Davood

    2017-05-01

    Wound healing is a complex and dynamic process following damage in tissue structures. Due to extensive skin damage caused by burn injuries, this study determined the role of human adult peripheral and umbilical cord blood platelet-rich plasma on proliferation and migration in human skin fibroblasts. Platelet-rich plasma (5, 10, 15, 20 and 50% PRP) from human umbilical cord blood and adult peripheral blood were provided and added to fibroblasts cultured from a human skin sample. Migration and proliferation of fibroblasts were assessed in comparison to 10% FBS and by the fibroblast responses to a concentration gradient. All components of the umbilical cord blood PRP significantly stimulated the growth of fibroblasts when compared to the negative control. Fibroblast growth was enhanced in a dose dependent manner. All fibroblast cultures retained normal morphology. No significant difference was noted between umbilical cord blood and adult peripheral blood PRP preparations regarding cell proliferation and migration, but the difference to 10% FBS was significant. 1% and 50% PRP reduced cellular proliferation. The 20% umbilical cord blood PRP and 10% adult peripheral blood PRP had a significant stimulatory effect on the migration of the skin fibroblast cells in comparison with 10% FBS. As PRP could promote the migration and proliferation of dermal fibroblasts, it can be safely added in cultures when treatment of chronic wounds without triggering the immune response is needed.

  19. Uterine pathologies to be considered before uterus-preserving surgery in cases of uterine prolapse

    Directory of Open Access Journals (Sweden)

    Fatma Eskicioğu

    2015-12-01

    Full Text Available Objective: Investigation of unpredictable risks due to abnormal uterine pathology after the choice of uterus-preserving reconstructive surgical procedure for women who have uterine prolapse and no other complaints was aimed. Methods: The data of 121 women (105 postmenopausal and 16 premenopausal who underwent vaginal hysterectomy due to pelvic organ prolapse was examined and the post-hysterectomy histopathology results were evaluated. Results: Senile cystic atrophy was the most common endometrial pathology result among postmenopausal women (63.5%. However, proliferative and secretory endometrium was the most common endometrial pathology finding among premenopausal women (81.3%. There were statistically significant differences between postmenopausal and perimenopausal women in terms of these pathology results (p0.05, myoma uteri was significantly more common in patients with perimenopause (p=0.01. Conclusion: The uterus must be evaluated in terms of endometrial pathologies in asymptomatic women with pelvic organ prolapse before uterus-preserving reconstructive surgical procedure, especially in postmenopausal period. J Clin Exp Invest 2015; 6 (4: 443-446

  20. The effect of electromagnetic field stimulation on the mRNA expression of fibroblast growth factor and it's receptor in bone marrow mesenchymal stem cells in vitro%电磁场对大鼠骨髓间充质干细胞成纤维细胞生长因子-2和成纤维细胞生长因子受体-2mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘朝旭; 杨勇; 虞冀哲; 李贵振; 郑亚东; 彭飞; 赵文春; 吴华

    2010-01-01

    目的 研究电磁场对体外培养的大鼠骨髓间充质干细胞(BMSCs)成纤维细胞生长因子-2(FGF-2)和成纤维细胞生长因子受体-2(FGFR-2)mRNA表达的影响.方法 体外分离培养大鼠骨髓间充质干细胞,取第3代细胞分组经电磁场暴磁处理,然后采用逆转录-聚合酶链反应(RT-PCR)技术分别检测各组细胞的FGF-2和FGFR-2 mRNA表达,并进行定量分析.结果 适当频率及作用时间的电磁场刺激可使大鼠骨髓间充质干细胞FGF-2和FGFR-2 mRNA表达明显增强.用15 Hz、1.0 mT电磁场刺激BMSCs.FGF-2mRNA的表达于10 min时达最大值,而FGFR-2 mRNA的表达则于30 min时达最大值;在50 Hz、1.0 mT电磁场的刺激下,FGF-2 mRNA的表达于60 min时达最大值,而FGFR-2 mRNA的表达则于30 min时达最大值;在75 Hz、1.0 mT电磁场的刺激下,FGF-2和FGFR-2 mRNA的表达均于30 min时达最大值;1.0 mT电磁场刺激30 min条件下,电磁场频率为50 Hz暴磁组BMSCs的FGF-2 mRNA的表达达最大值,而电磁场频率为75 Hz暴磁组BMSCs的FGFR-2 mRNA的表达达最大值.结论 适当"窗口"的电磁场刺激对体外培养的大鼠骨髓间充质干细胞FGF-2和FGFR-2 mRNA表达有明显的促进作用.%Objective To study the effects of an electromagnetic field (EMF) on the expression of fibro-blast growth factor (FGF-2) and it' s receptor (FGFR-2) mRNA in rat bone marrow mesenchymal stem cells (BMSCs) in vitro. Methods Rat BMSCs were isolated and cultured in vitro. The subcultured cells were divided into different groups to be EMF stimulated at 1.0 mT. The expression of FGF-2 and FGFR-2 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results Different frequencies and durations of 1.0 mT EMF exposure induced FGF-2 and FGFR-2 mRNA expression in comparison to blank controls. The expression of FGF-2 mRNA reached a peak after stimulation at 15 Hz for 10 min, 50 Hz for 60 min and 75 Hz for 30 min. And the expression of FGFR-2 mRNA reached a

  1. Inhibition by female sex hormones of collagen degradation by corneal fibroblasts.

    Science.gov (United States)

    Zhou, Hongyan; Kimura, Kazuhiro; Orita, Tomoko; Nishida, Teruo; Sonoda, Koh-Hei

    2011-01-01

    Corneal fibroblasts contribute to collagen remodeling in the corneal stroma in part by mediating collagen degradation. Given that corneal structure is influenced by sex hormone status, we examined the effects of sex hormones on collagen degradation by corneal fibroblasts. Rabbit corneal fibroblasts were cultured in three-dimensional collagen gels with or without sex hormones including 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA). Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression and activity of matrix metalloproteinases (MMPs) were evaluated by immunoblot analysis and gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) inhibitor NF kappa B Inhibitor-alpha (IκB-α) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively. 17β-Estradiol and progesterone each inhibited interleukin (IL)-1β-induced collagen degradation by corneal fibroblasts in a concentration-dependent manner, whereas testosterone and DHEA had no such effect. MMP expression and activation in corneal fibroblasts exposed to IL-1β were also inhibited by 17β-estradiol and progesterone. These female sex hormones did not affect cell proliferation or viability. Both 17β-estradiol and progesterone inhibited the IL-1β-induced phosphorylation of p38 MAPK without affecting that of the MAPKs extracellular Signal-regulated Kinase (ERK) or c-jun N-terminal kinase (JNK). 17β-Estradiol also inhibited the IL-1β-induced phosphorylation of IκB-α. 17β-Estradiol and progesterone inhibited MMP expression and activity in IL-1β-stimulated corneal fibroblasts and thereby suppressed collagen degradation by these cells.

  2. Establishing Primary Adult Fibroblast Cultures From Rodents

    Science.gov (United States)

    Seluanov, Andrei; Vaidya, Amita; Gorbunova, Vera

    2010-01-01

    The importance of using primary cells, rather than cancer cell lines, for biological studies is becoming widely recognized. Primary cells are preferred in studies of cell cycle control, apoptosis, and DNA repair, as cancer cells carry mutations in genes involved in these processes. Primary cells cannot be cultured indefinitely due to the onset of replicative senescence or aneuploidization. Hence, new cultures need to be established regularly. The procedure for isolation of rodent embryonic fibroblasts is well established, but isolating adult fibroblast cultures often presents a challenge. Adult rodent fibroblasts isolated from mouse models of human disease may be a preferred control when comparing them to fibroblasts from human patients. Furthermore, adult fibroblasts are the only available material when working with wild rodents where pregnant females cannot be easily obtained. Here we provide a protocol for isolation and culture of adult fibroblasts from rodent skin and lungs. We used this procedure successfully to isolate fibroblasts from over twenty rodent species from laboratory mice and rats to wild rodents such as beaver, porcupine, and squirrel. PMID:20972406

  3. [Heterogeneity of pulmonary fibroblasts in tuberculosis].

    Science.gov (United States)

    Kogan, E A; Sekamova, S M; Bogadel'nikova, I V; Vitukhnovskaia, L A; Fipps, R; Perel'man, M I; Serov, V V

    1997-01-01

    Chronic inflammation and pneumofibrosis are the central events in tuberculosis morphogenesis. It was suggested that a certain type of fibroblasts may play a role in chronization of the inflammation and development of sclerosis in tuberculosis. Fibrous tissue from the foci of secondary tuberculosis (fibrous-cavernous tuberculosis and tuberculomas) of 35 patients were studied light- and electron-microscopically and immunohistochemically. (THY 1-)fibroblasts non-containing lipids and producing insulin-like growth factor 2 (ILGF 2), binding proteins 2 and 4 and epidermal growth factor receptors were found in the foci of secondary tuberculosis close to the granulomatous inflammation and in the new and scarrous fibrous connective tissue of the tuberculoma capsule and caverna walls. These fibroblasts are able for auto- and paracrine regulation of the proliferation of fibroblasts, epithelium and other cells in the inflammatory foci. (THY 1+) fibroblasts containing lipids were observed in the foci of old sclerotic changes among the rough collagen fibres. Thus, (THY 1-) fibroblasts probably play a key role in chronization of inflammation, proliferation and pretumorous dysplasia of pulmonary epithelium in secondary tuberculosis. (THY 1+) fibroblasts containing lipids may show more pronounced collagenesis and may persist under hypoxia condition in the collagenous scars for a long time.

  4. Prostaglandin E₂ inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors.

    Science.gov (United States)

    Li, Ying-Ji; Wang, Xing-Qi; Sato, Tadashi; Kanaji, Nobuhiro; Nakanishi, Masanori; Kim, Miok; Michalski, Joel; Nelson, Amy J; Sun, Jian-Hong; Farid, Maha; Basma, Hesham; Patil, Amol; Toews, Myron L; Liu, Xiangde; Rennard, Stephen I

    2011-01-01

    The migration of fibroblasts is believed to play a key role in both normal wound repair and abnormal tissue remodeling. Prostaglandin E (PGE)(2), a mediator that can inhibit many fibroblast functions including chemotaxis, was reported to be mediated by the E-prostanoid (EP) receptor EP2. PGE(2), however, can act on four receptors. This study was designed to determine if EP receptors, in addition to EP2, can modulate fibroblast chemotaxis. Using human fetal lung fibroblasts, the expression of all four EP receptors was demonstrated by Western blotting. EP2-selective and EP4-selective agonists inhibited both chemotaxis toward fibronectin in the blindwell assay and migration in a wound-closure assay. In contrast, EP1-selective and EP3-selective agonists stimulated cell migration in both assay systems. These results were confirmed using EP-selective antagonists. The role of both EP2 and EP4 receptors in mediating the PGE(2) inhibition of chemotaxis was also confirmed by small interfering RNA suppression. Furthermore, the role of EP receptors was confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE(2) can act on multiple EP receptors in human lung fibroblasts, to exert disparate effects. Alterations in EP receptor expression may have the potential to alter PGE(2) action. Targeting specific EP receptors may offer therapeutic opportunities in conditions characterized by abnormal tissue repair and remodeling.

  5. Absence of K-Ras Reduces Proliferation and Migration But Increases Extracellular Matrix Synthesis in Fibroblasts.

    Science.gov (United States)

    Muñoz-Félix, José M; Fuentes-Calvo, Isabel; Cuesta, Cristina; Eleno, Nélida; Crespo, Piero; López-Novoa, José M; Martínez-Salgado, Carlos

    2016-10-01

    The involvement of Ras-GTPases in the development of renal fibrosis has been addressed in the last decade. We have previously shown that H- and N-Ras isoforms participate in the regulation of fibrosis. Herein, we assessed the role of K-Ras in cellular processes involved in the development of fibrosis: proliferation, migration, and extracellular matrix (ECM) proteins synthesis. K-Ras knockout (KO) mouse embryonic fibroblasts (K-ras(-/-) ) stimulated with transforming growth factor-β1 (TGF-β1) exhibited reduced proliferation and impaired mobility than wild-type fibroblasts. Moreover, an increase on ECM production was observed in K-Ras KO fibroblasts in basal conditions. The absence of K-Ras was accompanied by reduced Ras activation and ERK phosphorylation, and increased AKT phosphorylation, but no differences were observed in TGF-β1-induced Smad signaling. The MEK inhibitor U0126 decreased cell proliferation independently of the presence of K-ras but reduced migration and ECM proteins expression only in wild-type fibroblasts, while the PI3K-AKT inhibitor LY294002 decreased cell proliferation, migration, and ECM synthesis in both types of fibroblasts. Thus, our data unveil that K-Ras and its downstream effector pathways distinctively regulate key biological processes in the development of fibrosis. Moreover, we show that K-Ras may be a crucial mediator in TGF-β1-mediated effects in this cell type. J. Cell. Physiol. 231: 2224-2235, 2016. © 2016 Wiley Periodicals, Inc.

  6. Uterine morphology and peristalsis in women with polycystic ovary syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Leonhardt, Henrik; Hellstroem, Mikael [Department of Radiology, Institute of Clinical Sciences, Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden)], E-mail: henrik.leonhardt@vgregion.se; Gull, Berit; Nilsson, Lars; Janson, Per O. [Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Kishimoto, Keiko [Department of Radiology, St Marianna University School of Medicine, Kanagawa (Japan); Kataoka, Masako [Department of Radiology, Kyoto University Hospital, Kyoto (Japan); Stener-Victorin, Elisabet [Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden)

    2012-12-15

    Background. Polycystic ovary syndrome (PCOS) is associated with chronic oligo-anovulation and high circulating sex hormone levels. Women with PCOS have an increased risk of developing endometrial cancer. In anovulatory women with PCOS a positive relationship between endometrial thickness and endometrial hyperplasia has been observed. Uterine peristalsis, which has been suggested to be of importance for female fertility, has not previously been studied in PCOS. Purpose. To assess whether women with PCOS have altered endometrial thickness, uterine wall morphology, and peristalsis. Material and Methods. In this prospective case-control study 55 women with PCOS (mean age, 29.5 years {+-} 4.5 SD) and 28 controls (27.6 {+-} 3.2) were examined using magnetic resonance imaging (MRI), assessing thickness of endometrium, junctional zone (JZ), and myometrium, and evaluating the occurrence, frequency (waves/min), strength (amplitude), pattern, and direction of peristalsis. Uterine morphology was also assessed by transvaginal ultrasonography (TVUS). Results. The endometrium was thinner in PCOS with oligo-amenorrhea compared to controls, also after adjustments for age and BMI (adjusted P = 0.043). There was no difference in thickness of the JZ or the myometrium in cases versus controls. Uterine peristalsis was less commonly observed in women with PCOS than in controls (adjusted P = 0.014). Conclusion. There were no differences in myometrial morphology between PCOS and controls, but the endometrium was thinner in PCOS with oligo-amenorrhea. Based on cine MRI, uterine peristalsis was less common in PCOS than in controls.

  7. Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

    Science.gov (United States)

    Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

    2013-03-01

    Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

  8. Modified uterine allotransplantation and immunosuppression procedure in the sheep model.

    Directory of Open Access Journals (Sweden)

    Li Wei

    Full Text Available OBJECTIVE: To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. METHODS: In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. RESULTS: Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. CONCLUSION: We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.

  9. Modeling embryo transfer into a closed uterine cavity.

    Science.gov (United States)

    Yaniv, Sarit; Jaffa, Ariel J; Elad, David

    2012-11-01

    Embryo transfer (ET) is the last manual intervention after extracorporeal fertilization. After the ET procedure is completed, the embryos are conveyed in the uterus for another two to four days due to spontaneous uterine peristalsis until the window time for implantation. The role of intrauterine fluid flow patterns in transporting the embryos to their implantation site during and after ET was simulated by injection of a liquid bolus into a two-dimensional liquid-filled channel with a closed fundal end via a liquid-filled catheter inserted in the channel. Numerical experiments revealed that the intrauterine fluid field and the embryos transport pattern were strongly affected by the closed fundal end. The embryos re-circulated in small loops around the vicinity where they were deposited from the catheter. The transport pattern was controlled by the uterine peristalsis factors, such as amplitude and frequency of the uterine walls motility, as well as the synchronization between the onset of catheter discharge and uterine peristalsis. The outcome of ET was also dependent on operating parameters such as placement of the catheter tip within the uterine cavity and the delivery speed of the catheter load. In conclusion, this modeling study highlighted important parameters that should be considered during ET procedures in order to increase the potential for pregnancy success.

  10. Cine MR imaging of uterine peristalsis in patients with endometriosis

    Energy Technology Data Exchange (ETDEWEB)

    Kido, Aki; Togashi, Kaori; Koyama, Takashi; Fujimoto, Ryota [Kyoto University, Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto (Japan); Nishino, Mizuki [Beth Israel Deaconess Medical Center, Department of Radiology, Kyoto (Japan); Miyake, Kanae; Hayakawa, Katsumi [Kyoto City Hospital, Department of Radiology, Kyoto (Japan); Iwasaku, Kazuhiro [Kyoto City Hospital, Department of Obstetrics and Gynecology, Kyoto (Japan); Fujii, Shingo [Kyoto University, Department of Gynecology and Obstetrics, Kyoto (Japan)

    2007-07-15

    Endometriosis is one of the most important causes of infertility; however the precise mechanism by which it affects female fertility is unclear. The objective of this study was to study the functional aspects of the uterus by evaluating uterine contractility in patients with endometrial cysts of the ovary. The study population was recruited from two institutes and consisted of 26 women (periovulatory (10), luteal (13), and menstrual phase (3); age range: 19-51 years) with untreated endometriosis; the control group consisted of 12 healthy women (age range: 22-41 years). Cine MR imaging obtained by a 1.5T magnet was visually evaluated at 12 x faster than real speed, focusing on the presence of uterine peristalsis, the direction and frequency of peristalsis, and the presence of sustained uterine contractions. Uterine peristalsis was identifiable in 3/10, 3/13, and 3/3 of the endometriosis patients in each menstrual cycle, respectively, and in 11/12, 3/12, and 5/12 of their control subjects. Peristaltic detection rate and frequency were significantly less for the endometriosis group than for the controls in the periovulatory phase only (p<0.05). Sustained contractions were recognized in 19/36 control subjects and in 13/26 endometriosis patients, but the difference was not significant. Uterine peristalsis appears to be suppressed during the periovulatory phase in patients with endometriosis, which may have an adverse effect on sperm transport. (orig.)

  11. Uterine Closure in Cesarean Delivery: A New Technique

    Directory of Open Access Journals (Sweden)

    K M Babu

    2012-01-01

    Full Text Available Fear of scar rupture is one of risks involved in a post caesarean pregnancy. This had led to an increased rate of repeat cesarean delivery in today′s times. Closure of the uterine incision is a key step in cesarean section, and it is imperative that an optimal surgical technique be employed for closing a uterine scar. This technique should be able to withstand the stress of subsequent labor. In the existing techniques of uterine closure, single or double layer, correct approximation of the cut margins, that is, decidua-to-decidua, myometrium to myometrium, serosa to serosa is not guaranteed. Also, there are high chances of inter surgeon variability. It was felt that if a suturing technique which ensures correct approximation of all the layers mentioned above with nil or minimal possibility of inter operator variability existed, there will not be any thinning of lower segment caesarean section (LSCS. Further, a scarred uterus repaired in this manner will be able to withstand the stress of labor in future. We hereby report a new technique for uterine closure devised by us, which incorporates a continuous modified mattress suture technique as a modification of the existing surgical technique of uterine closure.

  12. [Cervical-uterine-cancer associated factors in Nayarit state, Mexico].

    Science.gov (United States)

    Aguirre Hernández, Raúl; Medina Carrillo, Leopoldo; Montoya Fuentes, Héctor; Sandoval López, José Guadalupe; Padilla Rosas, Miguel; García Silva, Valentín; Jáuregui Martínez, Armando

    2007-06-01

    To establish the association between high-grade intraepithelial lesions and cervical-uterine-cancer, and the infection by human papillomavirus, genetic antecedents, socioeconomics, sexual behavior and gynecology and obstetrics factors in women of the State of Nayarit, Mexico. With a case-control design were studied 66 cases of high-grade intraepithelial lesions and cervical-uterine-cancer, and 132 controls. The information upon the risk factors was obtained by the application of a structured questionnaire. Polymerase Chain Reaction executed the virus identification. In the statistical analysis the association was obtained by odds ratio. The statistical significance was evaluated by the chi-square-Fisher and Student t tests, and multivariate logistic regression was used to explain the factors' influence. In women with high-risk squamous intraepithelial lesions and cervical-uterine-cancer, the most frequently high-risk human papillomavirus found were: 18, 35, 58, 16, 31, 33 and 51. Familial data of cervical-uterine-cancer, socioeconomic level, number of sexual partners, data of sexual transmitted diseases, and infection due to human papillomavirus 18 and 35 are the factors related to high-risk squamous intraepithelial lesions and cervical-uterine-cancer.

  13. Sonographic evaluation of surgical repair of uterine cesarean scar defects.

    Science.gov (United States)

    Pomorski, Michal; Fuchs, Tomasz; Rosner-Tenerowicz, Anna; Zimmer, Mariusz

    2017-10-01

    The aim of the study was to assess the clinical outcomes of surgical repair of uterine cesarean scar defects with sonography (US). Seven nonpregnant women with history of cesarean section and a large uterine scar defect were enrolled. The surgical repair was performed by minilaparotomy. The US assessment of the uterine scar was performed using a standardized approach at baseline, then at a first visit 2-3 days following the surgical intervention (V1) and at a follow-up visit 3 months later (V2). Residual myometrial thickness (RMT), width, and depth of the scar defect were measured. The mean RMT increased significantly from 1.9 mm at baseline to 8.8 mm at V1 and 8.0 mm at V2. No intraoperative complications were observed. Postmenstrual spotting and abdominal pain reported preoperatively resolved after the operation. A surgical repair procedure for an incompletely healed uterine cesarean scar is effective in increasing RMT thickness, decreasing the depth of the scar, and reducing symptoms related to the cesarean section scar defect. Further studies on post-repair pregnancy outcomes are required to evaluate whether the procedure affects the rate of cesarean scar pregnancy, morbidly adherent placenta, and/or uterine scar dehiscence and rupture. The repair of a cesarean scar defect is recommended only for symptomatic women. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:455-460, 2017. © 2017 Wiley Periodicals, Inc.

  14. Prognostic features of surgical stage I uterine carcinosarcoma.

    Science.gov (United States)

    Ferguson, Sarah E; Tornos, Carmen; Hummer, Amanda; Barakat, Richard R; Soslow, Robert A

    2007-11-01

    Uterine carcinosarcomas (CSs) are aggressive neoplasms, with 5-year overall survival (OS) rates of less than 35%. They are customarily separated into types harboring either heterologous or homologous mesenchymal elements, but the prognostic significance of this finding is controversial. Our goal was to study clinicopathologic features of possible prognostic relevance in surgical stage I uterine CS. A retrospective clinical and histopathologic review was performed for all women diagnosed with surgical stage I uterine CS. These tumors were compared with stage I high-grade endometrial (HGEm) carcinomas for clinical outcomes. There were 42 cases of surgical stage I uterine CS identified between January 1990 and January 2004. The disease-free survival and OS rates for patients with stage I CS were significantly worse compared with stage I HGEm (P=0.001; P=0.01). The median disease-free survival for patients with heterologous CS was 15 months and had not been reached for women with homologous CS (P=0.001). The 3-year OS rates were 45% versus 93% in women with heterologous compared with homologous stage I CS (P90%. Homologous stage I CSs have survival outcomes that are similar to HGEm. This further supports the concept that homologous stage I CSs are carcinomas with sarcomatoid features, not sarcomas. More importantly, the presence of heterologous sarcomatous elements is a powerful negative prognostic factor in surgical stage I uterine CS.

  15. Maternal outcomes after uterine balloon tamponade for postpartum hemorrhage.

    Science.gov (United States)

    Martin, Emmanuelle; Legendre, Guillaume; Bouet, Pierre-Emmanuel; Cheve, Marie-Therese; Multon, Olivier; Sentilhes, Loïc

    2015-04-01

    To evaluate maternal outcomes following uterine balloon tamponade in the management of postpartum hemorrhage. Retrospective case-series. Two French hospitals, a level 3 university referral center and a level 2 private hospital. All women who underwent balloon tamponade treatment for primary postpartum hemorrhage. Uterine tamponade was used after standard treatment of postpartum hemorrhage had failed. The study population was divided into two groups, successful cases where the bleeding stopped after the balloon tamponade, and failures requiring subsequent surgery or embolization. Success rates. Uterine tamponade was used in 49 women: 30 (61%) after vaginal delivery and 19 (39%) after cesarean section. Uterine atony was the main cause of hemorrhage (86%). The overall success rate was 65%. Of 17 failures, surgery was required in 16 cases, including hysterectomy in 11, and uterine artery embolization in one case. Demographic and obstetric characteristics did not differ significantly between the success and failure groups. No complications were directly attributed to the balloon tamponade in the postpartum period. Two women had a subsequent full-term pregnancy without recurrence of postpartum hemorrhage. Balloon tamponade is an effective, safe and readily available method for treating primary postpartum hemorrhage and could reduce the need for invasive procedures. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  16. Wound healing and the role of fibroblasts.

    Science.gov (United States)

    Bainbridge, P

    2013-08-01

    Fibroblasts are critical in supporting normal wound healing, involved in key processes such as breaking down the fibrin clot, creating new extra cellular matrix (ECM) and collagen structures to support the other cells associated with effective wound healing, as well as contracting the wound. This article explores and summarises the research evidence on the role of fibroblasts, their origins and activation, and how they navigate the wound bed, as well as how their activity leads to wound contraction. This article also explores the local conditions at the wound site, which activate, regulate and ultimately reduce the fibroblast activity as the skin's integrity returns on healing.

  17. The Influence of Oxytocin on the Blood Perfusion of Uterine Fibroids: Contrast-enhanced Ultrasonography Evaluation

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2016-03-01

    Conclusion: This CEUS study demonstrated that the use of parenteral oxytocin can significantly reduce the blood perfusion of the uterine fibroids, which may help to enhance the therapeutic efficacy for high intensity focused ultrasound ablation of uterine fibroids.

  18. Comparison of 3 dimensional sonohysterography and hysteroscopy in Premenopausal women with abnormal uterine bleeding

    Directory of Open Access Journals (Sweden)

    Yasser I. Abd Elkhalek

    2016-09-01

    Conclusion: 3-D sonohysterography is a very safe, well tolerated and effective modality for evaluation of intracavitary uterine abnormalities and is an accurate alternative technique for hysteroscopy among the premenopausal women that suffers from abnormal uterine bleeding (AUB.

  19. The effect of peri-implantation administration of uterine relaxing agents in assisted reproduction treatment cycles: a systematic review and meta-analysis.

    Science.gov (United States)

    Khairy, Mohammed; Dhillon, Rima K; Chu, Justin; Rajkhowa, Madhurima; Coomarasamy, Arri

    2016-04-01

    Sub-endometrial junctional zone peristalsis is increased by ovarian stimulation and traumatic embryo transfer, and is linked with decreased implantation and pregnancy rates in assisted reproduction treatments. Various agents have been used to inhibit uterine hyper-peristalsis at the time of embryo transfer with conflicting results. This systematic review aimed to identify if uterine relaxants administered in the peri-implantation period during assisted reproduction treatments could improve pregnancy outcomes through literature search with no language restrictions. The review reports on 3546 patients in 17 randomized controlled trials published between 1993 and 2014. Women undergoing assisted reproduction techniques who either received a uterine relaxant agent in the peri-implantation period versus placebo or no treatment were included. Primary outcome was live birth rate. The meta-analyses did not show statistically significant benefit of any uterine relaxing agents on live birth rate. Other meta-analyses did not show a significant effect on the clinical pregnancy, spontaneous abortion, ectopic pregnancy and multiple pregnancy rate. Most of the included studies were of low quality and lacked significant power to detect minimally important effect. Evidence is insufficient to recommend using these agents in routine practice. Further methodologically robust randomized controlled trials with more refined selection criteria might reveal a beneficial effect.

  20. The effects of pomegranate seed extract and beta-sitosterol on rat uterine contractions.

    Science.gov (United States)

    Promprom, Wilawan; Kupittayanant, Pakanit; Indrapichate, Korakod; Wray, Susan; Kupittayanant, Sajeera

    2010-03-01

    The aim of this study was to investigate the effects of pomegranate (Punica granatum L., Punicaceae) seed extract on uterine contractility. Pomegranate seeds were methanolic extracted and their constituents analyzed using gas chromatography and mass spectrometry. Isometric force was measured in strips of longitudinal rat myometrium and the effects of pomegranate seed extract studied. We found beta-sitosterol to be the main constituent of the extract (16%) and its effects were also investigated. Pomegranate seed extract and beta-sitosterol increased spontaneous contractions in a concentration-dependent manner with a maximum effect at 250 mg/100 mL and 1 mg/100 mL, respectively. The amplitude and frequency of the phasic contraction were significantly increased along with basal tension. The effects of pomegranate seed extract were very similar to those of beta-sitosterol. Force produced in the presence of pomegranate seed extract was abolished by the inhibition of L-type calcium channels or myosin light chain kinase (MLCK). Contractions were not potentiated by pomegranate extract following the inhibition of K channels or inhibition of the sarcoplasmic reticulum calcium ATPase (SERCA). The actions of beta-sitosterol and the extract were not blocked by the estrogen receptor blocker, fulvestrant. We conclude that pomegranate seed extract is a potent stimulator of phasic activity in rat uterus. Our data suggest that the uterotonic effect is due to nonestrogenic effects of beta-sitosterol acting to inhibit K channels and SERCA and thereby increasing contraction via calcium entry on L-type calcium channels and MLCK. We suggest that pomegranate extract and beta-sitosterol may be a useful uterine stimulant.

  1. Depressive symptoms and risk of uterine leiomyomata.

    Science.gov (United States)

    Wise, Lauren A; Li, Se; Palmer, Julie R; Rosenberg, Lynn

    2015-05-01

    Uterine leiomyomata (UL) are a major source of gynecologic morbidity and the primary indication for hysterectomy. Depression can cause dysregulation of the hypothalamic-pituitary-adrenal axis, which may affect the synthesis of reproductive hormones involved in UL pathogenesis. We assessed the association between depressive symptoms and UL among 15,963 premenopausal women. Data were derived from the Black Women's Health Study, a prospective cohort study. In 1999 and 2005, the Center for Epidemiologic Studies Depression Scale (CES-D) was used to ascertain depressive symptoms. On biennial follow-up questionnaires from 1999 through 2011, women reported physician-diagnosed depression, antidepressant use, and UL diagnoses. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. There were 4722 incident UL cases diagnosed by ultrasound (n=3793) or surgery (n=929) during 131,262 person-years of follow-up. Relative to baseline CES-D scores<16, IRRs were 1.05 (95% CI, 0.98-1.13) for CES-D scores 16-24 and 1.16 (95% CI, 1.06-1.27) for CES-D scores≥25 (P-trend=.001). IRRs for current and past physician-diagnosed depression relative to no depression were 1.15 (95% CI, 0.98-1.34) and 1.25 (95% CI, 1.13-1.39), respectively. Results persisted after further control for antidepressant use. IRRs for current and past use of antidepressants (any indication) relative to never use were 1.11 (95% CI, 0.97-1.28) and 1.32 (95% CI, 1.14-1.52), respectively. In this cohort of black women, greater depressive symptoms were associated with UL, independent of antidepressant use, supporting the hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis increases UL risk. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. In vivo measurements of uterine cavities in 795 women of fertile age

    OpenAIRE

    Haspels, A A; Tadesse, E; Kurz, K.H.

    1984-01-01

    The uterine sound length, the functional length of the cervix including the zone of internal cervical os and the fundus transversal were determined in 795 fertile women in vivo using a measuring device, the Cavimeter. The functional cavity length was calculated by subtracting the functional length of the cervix from the uterine sound length. With growing parity, the uterine length and width increase, but with advance in age, the uterine cavity changes are not so distinct. The wide ranges foun...

  3. Targeted Delivery of Nanoparticles Bearing Fibroblast Growth Factor-2 by Ultrasonic Microbubble Destruction for Therapeutic Arteriogenesis

    Science.gov (United States)

    Chappell, John C.; Song, Ji; Burke, Caitlin W.

    2009-01-01

    Therapeutic strategies in which recombinant growth factors are injected to stimulate arteriogenesis in patients suffering from occlusive vascular disease stand to benefit from improved targeting, less invasiveness, better growth-factor stability, and more sustained growth-factor release. A microbubble contrast-agent-based system facilitates nanoparticle deposition in tissues that are targeted by 1-MHz ultrasound. This system can then be used to deliver poly(d,l-lactic-co-glycolic acid) nanoparticles containing fibroblast growth factor-2 to mouse adductor muscles in a model of hind-limb arterial insufficiency. Two weeks after treatment, significant increases in both the caliber and total number of collateral arterioles are observed, indicating that the delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction may represent an effective and minimally invasive strategy for the targeted stimulation of therapeutic arteriogenesis. PMID:18720443

  4. TRANSVAGINAL SONOGRAPHY COMBINED WITH SALINE CONTRAST SONOHYSTEROGRAPHY IN EVALUATING THE UTERINE CAVITY IN PREMENOPAUSAL PATIENTS WITH ABNORMAL UTERINE BLEEDING

    Directory of Open Access Journals (Sweden)

    K. G. M. Premleel

    2016-06-01

    Full Text Available OBJECTIVES To evaluate whether saline contrast sonohysterography (SCSH improved the diagnostic accuracy of transvaginal sonography (TVS for predicting endometrial abnormality in premenopausal patients with abnormal uterine bleeding. PATIENTS AND METHODS The uterine cavity was evaluated with TVS and SCSH in 60 premenopausal patients with abnormal uterine bleeding. All 58 patients underwent operative hysteroscopy or hysterectomy within 4 months which provided a detailed description of the uterine cavity and was used as the true value for exclusion of polyps and submucous myomas. RESULT Out of 60 patients, 45 had uterine abnormalities on TVS and SCSH and rest of the patients who appeared normal but had other abnormalities such as ovarian haemorrhagic cyst. Out of the 45 patients, 9 patients had submucous myomas and 9 were diagnosed as endometrial polyp. The findings were confirmed using hysterectomy/hysteroscopy/endometrial sampling. CONCLUSION The use of TVS without saline contrast left nine submucosal fibroids and five in nine of the polyps undiagnosed in referred patients with complaints of abnormal bleeding. It also helps in reducing the rate of more invasive procedures such as hysteroscopy. However, studies carried out for longer duration and large study population are required to validate our findings

  5. Diffusion-weighted imaging properties of uterine fibroids pre- and post-uterine fibroid embolisation

    Energy Technology Data Exchange (ETDEWEB)

    Kirpalani, Anish, E-mail: kirpalania@smh.ca [Department of Medical Imaging, University of Toronto, St. Michael’s Hospital, 30 Bond Street, 3CC, Toronto, ON M5B 1W8 (Canada); Chong, Jennifer [Department of Medical Imaging, University of Toronto, St. Michael’s Hospital, 30 Bond Street, 3CC, Toronto, ON M5B 1W8 (Canada); Yang, Natalie [Department of Radiology, Austin Health, Heidelberg, Victoria 3084 (Australia); Jenkins, Sarah J. [Department of Radiology, Memorial University of Newfoundland, St. John’s, NL A1B 3V6 (Canada); Nisenbaum, Rosane [Centre for Research on Inner City Health, the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Dalla Lana School of Public Health, University of Toronto, 30 Bond Street, Toronto, ON M5B 1W8 (Canada); Prabhudesai, Vikramaditya; Anthwal, Shalini; Colak, Errol [Department of Medical Imaging, University of Toronto, St. Michael’s Hospital, 30 Bond Street, 3CC, Toronto, ON M5B 1W8 (Canada)

    2014-09-15

    Highlights: • Change in ADC and contrast enhancement of uterine fibroids following UFE was studied. • ADC of fibroids rises post-UFE. Previous studies assessing this change have conflicting results. • ADC rise post-UFE is associated with degree of loss of contrast enhancement. • ADC measurement using DWI is not yet a proven replacement for GBCA-enhanced MRI. - Abstract: Objective: To determine the change in apparent diffusion coefficient (ADC) of uterine fibroids following uterine fibroid embolisation (UFE), and if the ADC change correlates with either volume loss or degree of contrast enhancement post-UFE. Materials and methods: This study was approved by our institutional review board with waiver of consent. The pel