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Sample records for human endometriosis relation

  1. Nutritional aspects related to endometriosis.

    PubMed

    Halpern, Gabriela; Schor, Eduardo; Kopelman, Alexander

    2015-01-01

    This literature review analyzed the evidence on nutritional aspects related to the pathogenesis and progression of endometriosis. Diets deficient in nutrients result in changes in lipid metabolism, oxidative stress and promote epigenetic abnormalities, that may be involved in the genesis and progression of the disease. Foods rich in omega 3 with anti-inflammatory effects, supplementation with N-acetylcysteine, vitamin D and resveratrol, in addition to the increased consumption of fruits, vegetables (preferably organic) and whole grains exert a protective effect, reducing the risk of development and possible regression of disease. Dietary re-education seems to be a promising tool in the prevention and treatment of endometriosis.

  2. Endometriosis

    MedlinePlus

    ... Related information Infertility fact sheet Menstruation and the menstrual cycle fact sheet Pregnancy Endometriosis on the fallopian tubes, ... periods that last more than seven days Short menstrual cycles (27 days or fewer) A family member (mother, ...

  3. Endometriosis

    MedlinePlus

    ... link between infertility and endometriosis? Almost 40% of women with infertility have endometriosis. Inflammation from endometriosis may damage the sperm or egg or interfere with their movement through the fallopian tubes and uterus. In severe ...

  4. Perfluoroalkyl substances and endometriosis-related infertility in Chinese women.

    PubMed

    Wang, Bin; Zhang, Rongrong; Jin, Fan; Lou, Hangying; Mao, Yuchan; Zhu, Wenting; Zhou, Wei; Zhang, Ping; Zhang, Jun

    2017-03-07

    Endometriosis is one of the main causes for female infertility. Previous studies suggested that perfluoroalkyl substances (PFASs), a group of ubiquitous environmental chemicals with properties of endocrine disruption and reproductive toxicity, were risk factors for endometriosis but there lacks direct evidence on the possible role of PFASs in endometriosis-related infertility. To fill this gap, we examined the association between PFASs and endometriosis-related infertility among Chinese reproductive-age women in a case-control study, which comprised 157 surgically confirmed endometriosis cases and 178 controls seeking infertility treatment because of male reproductive dysfunction in 2014 and 2015. Blood specimens were collected at the enrollment and analyzed for ten PFASs. Logistic regression was utilized to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for individual PFAS compound. Plasma concentrations of perfluorobutane sulfonic acid (PFBS) were associated with an increased risk of endometriosis-related infertility (second vs. lowest tertile: OR=3.74, 95% CI: 2.04, 6.84; highest vs. lowest tertile: OR=3.04, 95% CI: 1.65, 5.57). This association remained consistent when we restricted to subjects with no previous pregnancy (second vs. lowest tertile: OR=2.91, 95% CI: 1.28, 6.61; highest vs. lowest tertile: OR=3.41, 95% CI: 1.52, 7.65) or to subjects without other gynecologic pathology (second vs. lowest tertile: OR=4.65, 95% CI: 2.21, 9.82; highest vs. lowest tertile: OR=3.36, 95% CI: 1.58, 7.15). Plasma concentrations of perfluoroheptanoic acid (PFHpA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were inversely associated with endometriosis-related infertility, but the associations were attenuated in the sensitivity analyses. Our preliminary evidence suggests that exposure to PFBS may increase the risk of female infertility due to endometriosis. Future prospective studies are necessary to confirm these

  5. Effect of Letrozole on endometriosis-related pelvic pain

    PubMed Central

    Almassinokiani, Fariba; Almasi, Alireza; Akbari, Peyman; Saberifard, Mahboubeh

    2014-01-01

    Background: To determine the role of Letrozole, an aromatase inhibitor, in the treatment of endometriotic pain. Methods: In this prospective, randomized, controlled clinical trial in minimally invasive surgery research center, 51 women with pelvic endometriosis and endometriotic pain (dyspareunia, dysmenorrhea, pelvic pain) score of 5 or more (for at least one of these endometriotic pain), after laparoscopic diagnosis and conservative laparoscopic surgery were treated with either Letrozole plus OCP (n=25) or only OCP (n=26) for 4 months continuously. Results: Using VAS test, the score of dyspareunia, dysmenorrhea and pelvic pain 4 months after the laparoscopic surgery declined significantly in both groups but the difference between results of the two groups was not significant. Conclusion: Both treatment modalities showed comparable effectiveness in the treatment of pains related to endometriosis and in comparison with OCP, Letrozole did not affect the outcome. PMID:25664308

  6. An efficient model of human endometriosis by induced unopposed estrogenicity in baboons

    PubMed Central

    Nair, Hareesh B.; Baker, Robert; Owston, Michael A.; Escalona, Renee; Dick, Edward J.; VandeBerg, John L.; Nickisch, Klaus J.

    2016-01-01

    Endometriosis is a chronic estrogen-dependent disease that occurs in approximately 10% of reproductive age women. Baboons offer a clear benefit for studying the initiation and progression of endometriosis since baboon is very close to humans phylogenetically. Progestins are used in the treatment of endometriosis. The therapeutic window of progestins depends on the ratio of its affinity towards progesterone receptor agonism verses antagonism. The present study is to determine the role of pure antiprogestin in baboon endometriosis. We hypothesize that pure antiprogestin will induce unopposed estrogenicity and spontaneous endometriosis in baboons. The rate of endometrial invasion and attachment through modeled peritoneum in the presence and absence of progesterone and antiprogestin was evaluated in this study. A baboon model of endometriosis induced by unopposed estrogenicity using progesterone receptor antagonist (EC304) was used in this study. We observed EC304 has induced unopposed estrogenicity that deregulated proteins involved in attachment, invasion, cell growth, and steroid hormone receptors in this model. Our data suggest that depleting progesterone levels in the endometrium will increase estrogen hyper-responsiveness that leads to increased endometriotic lesion progression in the baboon (Papio anubis) model. This study reports a refined model of human endometriosis in baboons that could potentially be used to develop new diagnostic and therapeutic strategies for the benefit of women suffering from endometriosis. PMID:26908459

  7. Polymorphic variants in the dopamine receptor D2 in women with endometriosis-related infertility.

    PubMed

    Szczepańska, Malgorzata; Mostowska, Adrianna; Wirstlein, Przemyslaw; Skrzypczak, Jana; Misztal, Matthew; Jagodziński, Paweł P

    2015-08-01

    Data suggests that dopamine receptor DRD2 gene variants may contribute to hyperprolactinemia and that they may be risk factors for endometriosis-related infertility. The purpose of the present study was to determine whether nucleotide variants of the DRD2 gene may be associated with infertility related to endometriosis. Five DRD2 SNPs, rs1800497, rs6277, rs2283265, rs4245146 and rs4648317, which are located in different blocks of linkage disequilibrium, were studied in 151 cases and 381 controls. No significant differences between DRD2 rs1800497, rs6277, rs2283265, rs4245146 and rs4648317 genotype, allele nor haplotype frequencies were observed in women with endometriosis-related infertility compared with the control group. The present results did not confirm DRD2 gene variants to be genetic risk factors for endometriosis-related infertility.

  8. Effect of Human Umbilical Cord Mesenchymal Stem Cells Transplantation on Nerve Fibers of A Rat Model of Endometriosis

    PubMed Central

    Chen, Yan; Li, Dong; Zhang, Zhe; Takushige, Natsuko; Kong, Bei-Hua; Wang, Guo-Yun

    2015-01-01

    Background Endometriosis is a common, benign, oestrogen-dependent, chronic gynaecological disorder associated with pelvic pain and infertility. Some researchers have identified nerve fibers in endometriotic lesions in women with endometriosis. Mesenchymal stem cells (MSCs) have attracted interest for their possible use for both cell and gene therapies because of their capacity for self-renewal and multipotentiality of differentiation. We investigated how human umbilical cord-MSCs (hUC-MSCs) could affect nerve fibers density in endometriosis. Materials and Methods In this experimental study, hUC-MSCs were isolated from fresh human umbilical cord, characterized by flow cytometry, and then transplanted into surgically induced endometriosis in a rat model. Ectopic endometrial implants were collected four weeks later. The specimens were sectioned and stained immunohistochemically with antibodies against neurofilament (NF), nerve growth factor (NGF), NGF receptor p75 (NGFRp75), tyrosine kinase receptor-A (Trk-A), calcitonin gene-related peptide (CGRP) and substance P (SP) to compare the presence of different types of nerve fibers between the treatment group with the transplantation of hUC-MSCs and the control group without the transplantation of hUC-MSCs. Results There were significantly less nerve fibers stained with specific markers we used in the treatment group than in the control group (p<0.05). Conclusion MSC from human umbilical cord reduced nerve fiber density in the treatment group with the transplantation of hUC-MSCs. PMID:25918595

  9. Dioxin May Promote Inflammation-Related Development of Endometriosis

    PubMed Central

    Bruner-Tran, Kaylon L.; Yeaman, Grant R.; Crispens, Marta A.; Igarashi, Toshio M.; Osteen, Kevin G.

    2008-01-01

    Laboratory and population-based studies suggest that exposure to environmental toxicants may be one of several triggers for the development of endometriosis. We discuss evidence that modulation of the endometrial endocrine-immune interface could mechanistically link toxicant exposure to the development of this disease. Capsule Summary: Environmental toxicant exposure induces an inflammatory-like endometrial response that may promote the development of endometriosis. PMID:18394613

  10. Neuroendocrine and stress-related aspects of endometriosis.

    PubMed

    Luisi, Stefano; Pizzo, Alessandra; Pinzauti, Serena; Zupi, Errico; Centini, Gabriele; Lazzeri, Lucia; Di Carlo, Costantino; Petraglia, Felice

    2015-01-01

    Endometriosis is a model of a benign gynecologic disease associated with two major symptoms: pain and infertility. When becomes chronic, severe psychological and neuroendocrine changes may occur. The high levels of perceived stress caused by symptoms cause a neuroendocrine disequilibrium thus contributing to the progression of the disease. Elevated stress levels alter hormonal secretions, mood and behavior, sexual disorders and appetite custom. Inflammatory comorbidities may be associated with elevated stress in endometriotic patients (inflammatory bowel disease, fibromyalgia, chronic fatigue) and even autoimmune diseases (thyroid disease, systemic lupus erythematosus, multiple sclerosis). Neurogenic mechanisms are described in endometriotic lesions and they affect peripheral and central nervous system of these patients increasing pain sensitivity and stress reactivity. In conclusion, endometriosis is a disease which affects reproductive and neuroendocrine functions with a great impact on women's health and quality of life.

  11. Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

    PubMed Central

    Jafarabadi, Mina; Salehnia, Mojdeh; Sadafi, Rana

    2017-01-01

    Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN) and matrix metalloproteinase 2 (MMP2) genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03). Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments. PMID:28280797

  12. Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis.

    PubMed

    Aghajanova, L; Tatsumi, K; Horcajadas, J A; Zamah, A M; Esteban, F J; Herndon, C N; Conti, M; Giudice, L C

    2011-04-01

    Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P(4)) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P(4), we compared early (6-h), intermediate (48-h), and late (14-Day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESF) from women with endometriosis (hESF(endo)) with hESF from women without endometriosis (hESF(nonendo)). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESF were isolated and treated with P(4) (1 μM) plus estradiol (E(2)) (10 nM), E(2) alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P(4) in both hESF(nonendo) and hESF(endo), although a blunted response to P(4) was observed in the latter. The normal response of hESF to P(4) involves a tightly regulated kinetic cascade involving key components in the P(4) receptor and MAPK signaling pathways that results in inhibition of E(2)-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESF(endo) early response to P(4). The abnormal response of this cell type to P(4) may contribute to compromised embryonic implantation and infertility in women with endometriosis.

  13. Pathogenesis and the role of ARID1A mutation in endometriosis-related ovarian neoplasms

    PubMed Central

    Maeda, Daichi; Shih, Ie-Ming

    2012-01-01

    Endometriosis-related ovarian neoplasms (ERONs) are a unique group of tumors as they are associated with endometriosis, especially endometriosis presenting as an ovarian endometriotic cyst (endometrioma). ERONs include clear cell carcinoma, endometrioid carcinoma, and seromucinous borderline tumor. A growing body of evidence from both clinicopathological and molecular studies suggests that most, if not all, ERONs develop from endometriotic cyst epithelium through different stages of tumor progression. The endometriotic cyst contains abundant iron-induced reactive oxygen species which are thought to be mutagenic, and chronic exposure of cystic epithelium to this microenvironment facilitates the accumulation of somatic mutations that ultimately result in tumor development. Molecular analyses of ERONs, including genome-wide screens, have identified several molecular genetic alterations that lead to aberrant activation or inactivation of pathways involving ARID1A, PI3K, Wnt, and PP2A. Among all molecular genetic changes identified to date, inactivating mutations of the ARID1A tumor suppressor gene are the most common in ERON. Understanding the molecular changes and pathogenesis involved in the development of ERON is fundamental for future translational studies aimed at designing new diagnostic tests for early detection and identifying critical molecular features for targeted therapeutics. PMID:23232571

  14. What Are the Treatments for Endometriosis?

    MedlinePlus

    ... pelvic pain and endometriosis: Translational evidence of the relationship and implications. Human Reproduction Update, 17 (3), 327-346. [top] American College of Obstetricians and Gynecologists. (2010). Management of endometriosis (Practice Bulletin No. 114). Obstetrics & Gynecology, ...

  15. Priorities for Endometriosis Research

    PubMed Central

    Rogers, Peter A. W.; D’Hooghe, Thomas M.; Fazleabas, Asgerally; Gargett, Caroline E.; Giudice, Linda C.; Montgomery, Grant W.; Rombauts, Luk; Salamonsen, Lois A.; Zondervan, Krina T.

    2009-01-01

    Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:19196878

  16. ENVIRONMENTAL PCB EXPOSURE AND RISK OF ENDOMETRIOSIS

    EPA Science Inventory

    BACKGROUND: Hormonally active environmental agents recently have been associated with the development of endometriosis. METHODS: We undertook a study to assess the relation between endometriosis, an estrogen dependent gynecologic disease, and 62 individual polychlorinated biphe...

  17. Pain typology and incident endometriosis

    PubMed Central

    Schliep, K.C.; Mumford, S.L.; Peterson, C.M.; Chen, Z.; Johnstone, E.B.; Sharp, H.T.; Stanford, J.B.; Hammoud, A.O.; Sun, L.; Buck Louis, G.M.

    2015-01-01

    STUDY QUESTION What are the pain characteristics among women, with no prior endometriosis diagnosis, undergoing laparoscopy or laparotomy regardless of clinical indication? SUMMARY ANSWER Women with surgically visualized endometriosis reported the highest chronic/cyclic pain and significantly greater dyspareunia, dysmenorrhea, and dyschezia compared with women with other gynecologic pathology (including uterine fibroids, pelvic adhesions, benign ovarian cysts, neoplasms and congenital Müllerian anomalies) or a normal pelvis. WHAT IS KNOWN ALREADY Prior research has shown that various treatments for pain associated with endometriosis can be effective, making identification of specific pain characteristics in relation to endometriosis necessary for informing disease diagnosis and management. STUDY DESIGN, SIZE, DURATION The study population for these analyses includes the ENDO Study (2007–2009) operative cohort: 473 women, ages 18–44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at one of 14 surgical centers located in Salt Lake City, UT or San Francisco, CA. Women with a history of surgically confirmed endometriosis were excluded. PARTICIPANTS/MATERIALS, SETTING AND METHODS Endometriosis was defined as surgically visualized disease; staging was based on revised American Society for Reproductive Medicine (rASRM) criteria. All women completed a computer-assisted personal interview at baseline specifying 17 types of pain (rating severity via 11-point visual analog scale) and identifying any of 35 perineal and 60 full-body front and 60 full-body back sites for which they experienced pain in the last 6 months. MAIN RESULTS AND THE ROLE OF CHANCE There was a high prevalence (≥30%) of chronic and cyclic pelvic pain reported by the entire study cohort regardless of post-operative diagnosis. However, women with a post-operative endometriosis diagnosis, compared with women diagnosed with other gynecologic disorders or a normal pelvis

  18. Endometriosis: alternative methods of medical treatment

    PubMed Central

    Muñoz-Hernando, Leticia; Muñoz-Gonzalez, Jose L; Marqueta-Marques, Laura; Alvarez-Conejo, Carmen; Tejerizo-García, Álvaro; Lopez-Gonzalez, Gregorio; Villegas-Muñoz, Emilia; Martin-Jimenez, Angel; Jiménez-López, Jesús S

    2015-01-01

    Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included “endometriosis” matched with “medical treatment”, “new treatment”, “GnRH antagonists”, “Aromatase inhibitors”, “selective progesterone receptor modulators”, “anti-TNF α”, and “anti-angiogenic factors”. Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs. PMID:26089705

  19. Functional Analyses of Endometriosis-Related Polymorphisms in the Estrogen Synthesis and Metabolism-Related Genes

    PubMed Central

    Wang, Hsin-Shih; Wu, Hsien-Ming; Cheng, Bi-Hwa; Yen, Chih-Feng; Chang, Pi-Yueh; Chao, Angel; Lee, Yun-Shien; Huang, Hsien-Da; Wang, Tzu-Hao

    2012-01-01

    Endometriosis is determined by genetic factors, and the prevalence of genetic polymorphisms varies greatly depending on the ethnic group studied. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesis and metabolism and the risks of endometriosis. Three hundred patients with endometriosis and 337 non-endometriotic controls were recruited. Thirty four non-synonymous SNPs, which change amino acid residues, were analyzed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The functions of SNP-resulted amino acid changes were analyzed using multiple web-accessible databases and phosphorylation predicting algorithms. Among the 34 NCBI-listed SNPs, 22 did not exhibit polymorphism in this study of more than 600 Taiwanese Chinese women. However, homozygous and heterozygous mutants of 4 SNPs - rs6165 (genotype GG+GA, 307Ala/Ala+307Ala/Thr) of FSHR, rs 6166 (genotype GG+GA, 680Ser/Asn+680Ser/Ser) of FSHR, rs2066479 (genotype AA+AG, 289Ser/Ser+289Ser/Gly) of HSD17B3 and rs700519 (genotype TT+TC, 264Cys/Cys+264Cys/Arg) of CYP19, alone or in combination, were significantly associated with decreased risks of endometriosis. Bioinformatics results identified 307Thr of FSHR to be a site for O-linked glycosylation, 680Ser of FSHR a phosphorylated site by protein kinase B, and 289Ser of HSD17B3 a phosphorylated site by protein kinase B or ribosomal protein S6 kinase 1. Results of this study suggest that non-synonymous polymorphisms of FSHR, HSD17B3 and CYP19 genes may modulate the risk of endometriosis in Taiwanese Chinese women. Identification of the endometrosis-preferential non-synonymous SNPs and the conformational changes in those proteins may pave the way for the development of more disease-specific drugs. PMID:23139742

  20. Association between macrophage migration inhibitory factor in the endometrium and estrogen in endometriosis

    PubMed Central

    ZHANG, XIAO; MU, LIN

    2015-01-01

    Recent studies have shown that macrophage migration inhibitory factor (MIF) has a possible role in endometriosis-related pain and infertility, yet it has not been explored whether the mRNA level of MIF is altered in endometrial tissues from patients with endometriosis. The aim of the present study was to compare the expression of MIF in endometrial tissues from women with and without endometriosis, and to analyze the association between endometrial MIF expression and 17β-estradiol (E2). The protein and mRNA expression of MIF in the human endometrial tissue was assessed by western blotting and reverse transcription-polymerase chain reaction analysis, respectively. The MIF expression of women with endometriosis was found to be significantly higher than that of the controls. A positive correlation was noted between the serum E2 level and MIF expression. In endometrial cells from women with endometriosis, the level of E2-induced MIF upregulation was significantly higher than that in cells from women without endometriosis. In conclusion, this study demonstrated a significant increase in MIF expression in the endometrial tissues of women with endometriosis and an association between MIF expression and E2 level. MIF expression in endometrial cells from patients with endometriosis showed an increased sensitivity to stimulation by E2. PMID:26622394

  1. Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci

    PubMed Central

    Rahmioglu, Nilufer; Macgregor, Stuart; Drong, Alexander W.; Hedman, Åsa K.; Harris, Holly R.; Randall, Joshua C.; Prokopenko, Inga; Nyholt, Dale R.; Morris, Andrew P.; Montgomery, Grant W.; Missmer, Stacey A.; Lindgren, Cecilia M.; Zondervan, Krina T.

    2015-01-01

    Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10−3), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10−4). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10−4) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other. PMID:25296917

  2. Induction of endometriosis alters the peripheral and endometrial regulatory T cell population in the non-human primate

    PubMed Central

    Braundmeier, A.; Jackson, K.; Hastings, J.; Koehler, J.; Nowak, R.; Fazleabas, A.

    2012-01-01

    BACKGROUND Endometriosis is a gynecological condition that is characterized by extreme abdominal pain and also decreased fertility. Regulatory T cells (Tregs) have immunosuppressive activity critical for embryonic implantation and likewise the acceptance of tissue engraftment. Utilizing the induced non-human primate (Papio anubis) model of endometriosis, we hypothesize that endometriosis decreases the peripheral and endomet rial Treg profile, whereas ectopic lesions have increased Treg localization. METHODS Peripheral blood and endometrium were obtained throughout the menstrual cycle prior to and after induction of disease. Animals were randomly assigned to control (n = 7) or diseased (n = 16) treatment groups. Endometriosis was induced by i.p. injection of autologous menstrual tissue for 2 consecutive months during menses. Peripheral blood and endometrial tissue were collected at d9-11PO at 1, 3, 6, 9, 12 and 15 months post-induction of disease for fluorescence-activated cell sorting, quantitative RT–PCR and immunohistochemistry. Ectopic lesions were excised at 1 and 6 months post-inoculation and also harvested at necropsy (15 months) and processed for RNA of IHC. Identification of Tregs through analysis of FOXP3 expression was conducted utlilizing several methodologies. Differences were determined by non-parametric statistical analysis between all treatment groups and time points. RESULTS In control animals, the proportion of peripheral natural Tregs (nTregs) was reduced (P < 0.05) during the mid- and late secretory stages of the menstrual cycle compared with menses. The induction of disease decreased peripheral Treg expression at early time points (P < 0.05) and this remained low throughout the time course, compared with the pre-inoculatory level of an individual. FOXP3 gene expression and Treg populations were also decreased in the eutopic endometrium (P < 0.05) compared with control animals, whereas these parameters were increased in ectopic lesions (P < 0

  3. Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain

    PubMed Central

    Maia, Hugo; Haddad, Clarice; Casoy, Julio

    2014-01-01

    Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB) activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster) acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3) or in association with Pycnogenol (groups 2 and 4), resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4) compared with those using oral contraceptives alone (groups 1 and 3). In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain. PMID:24379702

  4. Altered expression of progesterone receptor isoforms A and B in human eutopic endometrium in endometriosis patients.

    PubMed

    Wölfler, Monika Martina; Küppers, Mareike; Rath, Werner; Buck, Volker Uwe; Meinhold-Heerlein, Ivo; Classen-Linke, Irmgard

    2016-07-01

    Recent data implicate an altered expression of progesterone receptor isoform A (PR-A) and B (PR-B) in the endometrium of endometriosis patients. This prospective exploratory study aimed to precisely determine the PR-A and PR-B expression using immunohistochemical techniques in eutopic endometrium of women with endometriosis compared with disease-free women throughout the menstrual cycle. All symptomatic patients underwent laparoscopy for the diagnosis of endometriosis and histological confirmation of the disease (EO) whereas controls were proven disease-free (CO). In CO samples (n=10) an increased expression of PR-A and PR-B during the proliferative to early secretory phase and a decreased expression of both receptor isoforms during the mid to late secretory phase was ascertained in accordance with previous studies. In patients with endometriosis (n=16) no cycle dependent pattern of PR-A and PR-B expression was identified in contrast to patients without endometriosis. Moreover, in EO samples a huge variety of inter- and intra-individual differences in PR-A and PR-B expression were detected. These data provide further evidence that dysregulation of the PR-A and PR-B expression might contribute to the pathophysiology of endometriosis.

  5. Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis.

    PubMed

    Ruiz, A; Rockfield, S; Taran, N; Haller, E; Engelman, R W; Flores, I; Panina-Bordignon, P; Nanjundan, M

    2016-01-14

    In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein 1 light-chain 3β; an autophagic marker) was increased in uterine horns of endometriosis-induced mice compared with uterine horns of controls. By immunohistochemical staining of a human endometriosis-focused tissue microarray, we observed LC3B expression predominantly in epithelial relative to stromal cells in both eutopic and ectopic endometria. Via transmission electron microscopy, cells from eutopic endometria of endometriosis-induced mice contained more lipid droplets (rather than autophagosomes) compared with uterine horns from controls. Collectively, our findings indicate that the autophagic pathway is dysregulated in both ectopic and eutopic endometrium in a murine model of endometriosis and that HCQ has potential as a therapeutic agent for women afflicted with endometriosis.

  6. Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis

    PubMed Central

    Ruiz, A; Rockfield, S; Taran, N; Haller, E; Engelman, R W; Flores, I; Panina-Bordignon, P; Nanjundan, M

    2016-01-01

    In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein 1 light-chain 3β; an autophagic marker) was increased in uterine horns of endometriosis-induced mice compared with uterine horns of controls. By immunohistochemical staining of a human endometriosis-focused tissue microarray, we observed LC3B expression predominantly in epithelial relative to stromal cells in both eutopic and ectopic endometria. Via transmission electron microscopy, cells from eutopic endometria of endometriosis-induced mice contained more lipid droplets (rather than autophagosomes) compared with uterine horns from controls. Collectively, our findings indicate that the autophagic pathway is dysregulated in both ectopic and eutopic endometrium in a murine model of endometriosis and that HCQ has potential as a therapeutic agent for women afflicted with endometriosis. PMID:26775710

  7. Effects of Vitamin D on Endometriosis-Related Pain: A Double-Blind Clinical Trial

    PubMed Central

    Almassinokiani, Fariba; Khodaverdi, Sepideh; Solaymani-dodaran, Masoud; Akbari, Peyman; Pazouki, Abdolreza

    2016-01-01

    Background Endometriosis is a disabling disease of reproductive-age women. Dysmenorrhea, dyspareunia, and pelvic pain are the main symptoms of endometriosis. Its etiology is not clear. Endometriosis may have various causes, including vitamin D deficiency, but its effect is controversial. Material/Methods In this double-blind clinical trial, we enrolled patients with endometriosis diagnosed and treated by laparoscopy, with scores of at least 3 for of dysmenorrhea and/or pelvic pain at 8 weeks after surgical treatment. They were randomly prescribed vitamin D (50 000 IU weekly for 12 weeks) or placebo. Severity of pain in the 2 groups (placebo and treatment) was compared by VAS test at 24 weeks after surgical treatment. Results There were 19 patients in the vitamin D group and 20 in the placebo group. Baseline characteristics in the 2 groups were similar. Following the treatment with vitamin D or placebo, we did not find significant differences in severity of pelvic pain (p=0.24) and dysmenorrhea (p=0.45) between the 2 groups. Mean pelvic pain at 24 weeks after laparoscopy in the vitamin D group was 0.84±1.74 and in placebo group it was 0.68±1.70 (p=0.513). Mean dysmenorrhea was 2.10±2.33 in the vitamin D group and 2.73±2.84 in the placebo group (p=0.45). Conclusions After ablative surgery for endometriosis, vitamin D treatment did not have a significant effect in reducing dysmenorrhea and/or pelvic pain. PMID:27986972

  8. Relating Chronic Pelvic Pain and Endometriosis to Signs of Sensitization and Myofascial Pain and Dysfunction.

    PubMed

    Aredo, Jacqueline V; Heyrana, Katrina J; Karp, Barbara I; Shah, Jay P; Stratton, Pamela

    2017-01-01

    Chronic pelvic pain is a frustrating symptom for patients with endometriosis and is frequently refractory to hormonal and surgical management. While these therapies target ectopic endometrial lesions, they do not directly address pain due to central sensitization of the nervous system and myofascial dysfunction, which can continue to generate pain from myofascial trigger points even after traditional treatments are optimized. This article provides a background for understanding how endometriosis facilitates remodeling of neural networks, contributing to sensitization and generation of myofascial trigger points. A framework for evaluating such sensitization and myofascial trigger points in a clinical setting is presented. Treatments that specifically address myofascial pain secondary to spontaneously painful myofascial trigger points and their putative mechanisms of action are also reviewed, including physical therapy, dry needling, anesthetic injections, and botulinum toxin injections.

  9. Endometriosis-Related Infertility: The Role of the Assisted Reproductive Technologies

    PubMed Central

    Surrey, Eric S.

    2015-01-01

    The assisted reproductive technologies, particularly in vitro fertilization (IVF), represent the most efficient and successful means of overcoming infertility associated with endometriosis. Although older studies suggest that IVF outcomes are compromised in endometriosis patients, more contemporary reports show no differences compared to controls. The exception may be evidence of poorer outcomes and diminished ovarian response in women with advanced disease, particularly those with significant ovarian involvement or prior ovarian surgery. Prolonged pre-IVF cycle suppressive medical therapy, particularly gonadotropin releasing hormone agonists, appears to improve success rates in a subset of endometriosis patients. However, as of yet, there is no diagnostic marker to specifically identify those who would most benefit from this approach. Pre-IVF cycle surgical resection of nonovarian disease has not been consistently shown to improve outcomes with the possible exception of resection of deeply invasive disease, although the data is limited. Precycle resection of ovarian endometriomas does not have benefit and should only be performed for gynecologic indications. Indeed, there is a large body of evidence to suggest that this procedure may have a deleterious impact on ovarian reserve and response. A dearth of appropriately designed trials makes development of definitive treatment paradigms challenging. PMID:26240824

  10. Stretch magnitude- and frequency-dependent cyclooxygenase 2 and prostaglandin E2 up-regulation in human endometrial stromal cells: possible implications in endometriosis.

    PubMed

    Li, Xiaochuan; Gong, Xianghui; Zhu, Lan; Leng, Jinhua; Fan, Qingbo; Sun, Dawei; Lang, Jinghe; Fan, Yubo

    2012-11-01

    Endometriosis, with a prevalence rate ranging from 6% to 10%, is the major contributor to pelvic pain and subfertility, and considerably reduces the quality of life in affected women. However, the pathogenesis of this disease remains largely unknown. The present study aimed to uncover the role of hyperperistalsis in the pathogenesis of endometriosis, by exploring the response of human endometrial stromal cells (ESCs) to the cyclic stretch in vitro. ESCs isolated from 18 different endometrium biopsies undergoing hysterectomy for myoma were subjected to uniaxial cyclic stretches with different magnitude and frequency using the Uniaxial Tension System. Expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in stretched and unstretched ESCs were assessed by realtime quantitative polymerase chain reaction and Western blot. Production of prostaglandin E2 (PGE(2)) in the culture medium was measured by enzyme-linked immunosorbent assay. The cyclic stretch mimicking hyperperistalsis in endometriosis (5% elongation at 4 cycles/min) stimulated quick up-regulations of COX-2 and mPGES-1 simultaneously on both transcriptional and translational levels, and delayed PGE(2) overproduction was also noted in ESCs. As the stretch magnitude or frequency increased, so did overexpression of COX-2 and PGE(2) (P < 0.05). By contrast, the cyclic stretch mimicking physiological peristalsis (3% elongation at 2 cycles/min) did not induce significant COX-2, mPGES-1 or PGE(2) production within 12 h. Both COX-2 and mPEGS-1 are PGE(2) synthases, and the aberrant COX-2 and PGE(2) production play important roles in the pathogenesis of endometriosis. Therefore, the present findings revealed that increased stretch stimuli from the hyperperistalsis of endometriosis were capable of causing the aberrant COX-2 and PGE(2) expression in the endometrium by mechanotransduction, in a magnitude and frequency-dependent manner. It implied possible roles of hyperperistalsis in

  11. Molecular profiling of experimental endometriosis identified gene expression patterns in common with human disease

    PubMed Central

    Flores, Idhaliz; Rivera, Elizabeth; Ruiz, Lynnette A.; Santiago, Olga I.; Vernon, Michael W.; Appleyard, Caroline B.

    2007-01-01

    OBJECTIVE To validate a rat model of endometriosis using cDNA microarrays by identifying common gene expression patterns beween experimental and natural disease. DESIGN Autotransplantation rat model. SETTING Medical school department. ANIMALS Female Sprague-Dawley rats. INTERVENTIONS Endometriosis was surgically-induced by suturing uterine horn implants next to the small intestine’s mesentery. Control rats received sutures with no implants. After 60 days, endometriotic implants and uterine horn were obtained. MAIN OUTCOME MEASURES Gene expression levels determined by cDNA microarrays and QRT-PCR. METHODS Cy5-labeled cDNA was synthesized from total RNA obtained from endometriotic implants. Cy3-labeled cDNA was synthesized using uterine RNA from a control rat. Gene expression levels were analyzed after hybridizing experimental and control labeled cDNA to PIQOR™ Toxicology Rat Microarrays (Miltenyi Biotec) containing 1,252 known genes. Cy5/Cy3 ratios were determined and genes with >2-fold higher or <0.5-fold lower expression levels were selected. Microarray results were validated by QRT-PCR. RESULTS We observed differential expression of genes previously shown to be upregulated in patients, including growth factors, inflammatory cytokines/receptors, tumor invasion/metastasis factors, adhesion molecules, and anti-apoptotic factors. CONCLUSIONS This study presents evidence in support of using this rat model to study the natural history of endometriosis and test novel therapeutics for this incurable disease. PMID:17478174

  12. Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial

    PubMed Central

    2011-01-01

    reduce the intensity of endometriosis-related pain symptoms. Combining letrozole with oral norethisterone acetate was associated with a lower incidence of adverse effects and a lower discontinuation rate than combining letrozole with triptorelin. PMID:21693037

  13. Endometriosis among Women Exposed to Polybrominated Biphenyls

    PubMed Central

    Hoffman, Caroline S.; Small, Chanley M.; Blanck, Heidi Michels; Tolbert, Paige; Rubin, Carol; Marcus, Michele

    2007-01-01

    Purpose We examined the association between endometriosis and exposure to polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) among women inadvertently exposed to PBBs in 1973. Methods Serum PBB and PCB were measured in the late 1970s. Women self-reported endometriosis at interview in 1997. We constructed Cox models to estimate the relative incidence of endometriosis in relation to PBB and PCB levels. Results Seventy-nine of 943 women (9%) reported endometriosis. Compared to women with low PBB exposure (≤ 1 parts per billion [ppb]), women with moderate PBB (1–4 ppb) (hazard ratio [HR] = 0.72; 95% confidence interval [CI], 0.39–1.31) and high PBB (≥ 4 ppb) (HR = 0.90; 95% CI, 0.51–1.59) exposure did not have increased incidence of endometriosis. Increased incidence of endometriosis was suggested among women exposed to moderate PCB (5–8 ppb) (HR = 1.67; 95% CI, 0.91–3.10) and high PCB (≥ 8 ppb) (HR = 1.68; 95% CI, 0.95–2.98) levels compared to low PCB exposure (≤ 5 ppb). Conclusions Our study does not support an association between PBB exposure and endometriosis. Findings for serum PCB level are consistent with an emerging body of literature suggesting an association between PCB exposure and endometriosis. PMID:17448678

  14. Expression of human aldo-keto reductase 1C2 in cell lines of peritoneal endometriosis: potential implications in metabolism of progesterone and dydrogesterone and inhibition by progestins.

    PubMed

    Beranič, Nataša; Brožič, Petra; Brus, Boris; Sosič, Izidor; Gobec, Stanislav; Lanišnik Rižner, Tea

    2012-05-01

    The human aldo-keto reductase AKR1C2 converts 5α-dihydrotestosterone to the less active 3α-androstanediol and has a minor 20-ketosteroid reductase activity that metabolises progesterone to 20α-hydroxyprogesterone. AKR1C2 is expressed in different peripheral tissues, but its role in uterine diseases like endometriosis has not been studied in detail. Some progestins used for treatment of endometriosis inhibit AKR1C1 and AKR1C3, with unknown effects on AKR1C2. In this study we investigated expression of AKR1C2 in the model cell lines of peritoneal endometriosis, and examined the ability of recombinant AKR1C2 to metabolise progesterone and progestin dydrogesterone, as well as its potential inhibition by progestins. AKR1C2 is expressed in epithelial and stromal endometriotic cell lines at the mRNA level. The recombinant enzyme catalyses reduction of progesterone to 20α-hydroxyprogesterone with a 10-fold lower catalytic efficiency than the major 20-ketosteroid reductase, AKR1C1. AKR1C2 also metabolises progestin dydrogesterone to its 20α-dihydrodydrogesterone, with 8.6-fold higher catalytic efficiency than 5α-dihydrotestosterone. Among the progestins that are currently used for treatment of endometriosis, dydrogesterone, medroxyprogesterone acetate and 20α-dihydrodydrogesterone act as AKR1C2 inhibitors with low μM K(i) values in vitro. Their potential in vivo effects should be further studied.

  15. Peritoneal Fluid Reduces Angiogenesis-Related MicroRNA Expression in Cell Cultures of Endometrial and Endometriotic Tissues from Women with Endometriosis

    PubMed Central

    Braza-Boïls, Aitana; Gilabert-Estellés, Juan; Ramón, Luis A.; Gilabert, Juan; Marí-Alexandre, Josep; Chirivella, Melitina; España, Francisco; Estellés, Amparo

    2013-01-01

    Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent gynecological diseases. It has been suggested that modifications of both endometrial and peritoneal factors could be implicated in this disease. Endometriosis is a multifactorial disease in which angiogenesis and proteolysis are dysregulated. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the protein expression and may be the main regulators of angiogenesis. Our hypothesis is that peritoneal fluid from women with endometriosis could modify the expression of several miRNAs that regulate angiogenesis and proteolysis in the endometriosis development. The objective of this study has been to evaluate the influence of endometriotic peritoneal fluid on the expression of six miRNAs related to angiogenesis, as well as several angiogenic and proteolytic factors in endometrial and endometriotic cell cultures from women with endometriosis compared with women without endometriosis. Methods Endometrial and endometriotic cells were cultured and treated with endometriotic and control peritoneal fluid pools. We have studied the expression of six miRNAs (miR-16, -17-5p, -20a, -125a, -221, and -222) by RT-PCR and protein and mRNA levels of vascular endothelial growth factor-A, thrombospondin-1, urokinase plasminogen activator and plasminogen activator inhibitor-1 by ELISA and qRT-PCR respectively. Results Control and endometriotic peritoneal fluid pools induced a significant reduction of all miRNAs levels in endometrial and endometriotic cell cultures. Moreover, both peritoneal fluids induced a significant increase in VEGF-A, uPA and PAI-1 protein levels in all cell cultures without significant increase in mRNA levels. Endometrial cell cultures from patients treated with endometriotic peritoneal fluid showed lower expression of miRNAs and higher expression of VEGF-A protein levels than cultures from controls. In conclusion, this “in vitro” study indicates that

  16. Dioxins and endometriosis: a plausible hypothesis.

    PubMed Central

    Birnbaum, Linda S; Cummings, Audrey M

    2002-01-01

    A potential connection exists between exposure to organochlorine chemicals and the increasing prevalence of endometriosis. Evidence shows that dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of endometrial tissue implanted into rodents in a surgically induced model of endometriosis. The mechanism of the connection between organochlorine chemicals and endometriosis is not clear. Effects on growth factors, cytokines, and hormones (components of the immune and endocrine systems) are potential means of mediating the possible promotion of endometriosis by dioxins. Studies on epidemiology and on structure-activity relationships of organochlorine chemicals and endometriosis have been additional approaches to this problem. In this regard, toxic equivalence (TEQ) appears to be an important determinant of the effects of organochlorine chemicals on endometriosis. In this article, we review the literature related to endometriosis and dioxins and attempt to integrate the various sources of information that bolster the hypothesis connecting dioxins and endometriosis. PMID:11781160

  17. Endometriosis, Angiogenesis and Tissue Factor

    PubMed Central

    Krikun, Graciela

    2012-01-01

    Tissue factor (TF), is a cellular receptor that binds the factor VII/VIIa to initiate the blood coagulation cascade. In addition to its role as the initiator of the hemostatic cascade, TF is known to be involved in angiogenesis via intracellular signaling that utilizes the protease activated receptor-2 (PAR-2). We now review the physiologic expression of TF in the endometrium and its altered expression in multiple cell types derived from eutopic and ectopic endometrium from women with endometriosis compared with normal endometrium. Our findings suggest that TF might be an ideal target for therapeutic intervention in endometriosis. We have employed a novel immunoconjugate molecule known as Icon and were able to eradicate endometrial lesions in a mouse model of endometriosis without affecting fertility. These findings have major implications for potential treatment in humans. PMID:24278684

  18. A baboon model for endometriosis: implications for fertility

    PubMed Central

    Hastings, Julie M; Fazleabas, Asgerally T

    2006-01-01

    Endometriosis is one of the most common causes of chronic pelvic pain and infertility in women in the reproductive age group. Although the existence of this disease has been known for over 100 years our current knowledge of its pathogenesis and the pathophysiology of its related infertility remains unclear. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed a model of this disease in the non-human primate, the baboon (Papio anubis). Intraperitoneal inoculation of autologous menstrual endometrium results in the development of endometriotic lesions with gross morphological characteristics similar to those seen in the human. Multiple factors have been implicated in endometriosis-associated infertility. We have described aberrant levels of factors involved in multiple pathways important in the establishment of pregnancy, in the endometrium of baboons induced with endometriosis. Specifically, we have observed dysregulation of proteins involved in invasion, angiogenesis, methylation, cell growth, immunomodulation, and steroid hormone action. These data suggest that, in an induced model of endometriosis in the baboon, an increased angiogenic capacity, decreased apoptotic potential, progesterone resistance, estrogen hyper-responsiveness, and an inability to respond appropriately to embryonic signals contribute to the reduced fecundity associated with this disease. PMID:17118171

  19. Endometriosis and the adolescent.

    PubMed

    Dovey, Serena; Sanfilippo, Joseph

    2010-06-01

    The majority of women with endometriosis report symptoms starting in adolescence, yet endometriosis is often a delayed diagnosis in this patient population. Given that endometriosis is felt to be a progressive disease with increasing morbidities over time, such as structural defects and infertility, being more aggressive with pursuing the diagnosis is warranted. Once the diagnosis of endometriosis is made, various medical and surgical treatment modalities are available, and this article will review the most current treatment recommendations.

  20. Endometriosis-associated Maternal Pregnancy Complications – Case Report and Literature Review

    PubMed Central

    Petresin, J.; Wolf, J.; Emir, S.; Müller, A.; Boosz, A. S.

    2016-01-01

    The incidence of endometriosis is increasing. Particularly during pregnancy and labour, clinicians should be alert to possible endometriosis-associated complications or complications of previous endometriosis treatment, despite a low relative risk. In addition to an increased rate of early miscarriage, complications such as spontaneous bowel perforation, rupture of ovarian cysts, uterine rupture and intraabdominal bleeding from decidualised endometriosis lesions or previous surgery are described in the literature. Unfavourable neonatal outcomes have also been discussed. We report on an irreducible ovarian torsion in the 16th week of pregnancy following extensive endometriosis surgery, and an intraabdominal haemorrhage due to endometriosis of the bowel in the 29th week of pregnancy. PMID:27570252

  1. Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions.

    PubMed

    Cakmak, Hakan; Taylor, Hugh S

    2010-01-01

    HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, where they are necessary for endometrial growth, differentiation, and implantation. In human endometrium, the expression of HOXA10 and HOXA11 is driven by sex steroids, with peak expression occurring at time of implantation in response to rising progesterone levels. However, the maximal HOXA10 and HOXA11 expression fails to occur in women with endometriosis. In endometriosis, altered progesterone receptor expression or diminished activity may lead to attenuated or dysregulated progesterone response and decreased expression of progesterone-responsive genes including HOX genes in the eutopic endometrium. In turn, other mediators of endometrial receptivity that are regulated by HOX genes, such as pinopodes, alphavbeta3 integrin, and IGFBP-1, are downregulated in endometriosis. HOXA10 hypermethylation has recently been demonstrated to silence HOXA10 gene expression and account for decreased HOXA10 in the endometrium of women with endometriosis. Silencing of progesterone target genes by methylation is an epigenetic mechanism that mediates progesterone resistance. The relatively permanent nature of methylation may explain the widespread failure of treatments for endometriosis-related infertility.

  2. Deficiency of immunophilin FKBP52 promotes endometriosis.

    PubMed

    Hirota, Yasushi; Tranguch, Susanne; Daikoku, Takiko; Hasegawa, Akiko; Osuga, Yutaka; Taketani, Yuji; Dey, Sudhansu K

    2008-12-01

    Endometriosis is a common gynecological disease that affects approximately 10% of women of childbearing age. It is characterized by endometrial growth outside the uterus and often results in inflamed lesions, pain, and reduced fertility. Although heightened estrogenic activity and/or reduced progesterone responsiveness are considered to be involved in the etiology of endometriosis, neither the extent of their participation nor the underlying mechanisms are clearly understood. Heterogeneous uterine cell types differentially respond to estrogen and progesterone (P(4)). P(4), primarily acting via its nuclear receptor (PR), activates gene transcription and impacts many reproductive processes. Deletion of Fkbp52, an immunophilin cochaperone for PR, results in uterine-specific P(4) resistance in mice, creating an opportunity to study the unique aspects of P(4) signaling in endometriosis. Here we explored the roles of FKBP52 in this disease using Fkbp52(-/-) mice. We found that the loss of FKBP52 encourages the growth of endometriotic lesions with increased inflammation, cell proliferation, and angiogenesis. We also found remarkable down-regulation of FKBP52 in cases of human endometriosis. Our results provide the first evidence corroborated by genetic studies in mice for a potential role of an immunophilin cochaperone in the etiology of human endometriosis. This investigation is highly relevant for clinical application, particularly because P(4) resistance is favorably indicated in endometriosis and other gynecological diseases.

  3. Endometrioid adenocarcinoma arising from endometriosis of the rectosigmoid.

    PubMed

    Kobayashi, Shigeru; Sasaki, Morio; Goto, Tatsuya; Asakage, Naoki; Sekine, Masayuki; Suzuki, Takahisa; Tsukada, Kenji; Yamasaki, Shigetaka; Ukawa, Shiro

    2010-01-01

    A case of endometrioid adenocarcinoma supposedly arising from endometriosis of the rectum is reported. Malignant transformation is uncommon but a well-known complication of endometriosis. In the present case, it was proved by histopathological findings and immunophenotype such as cytokeratin7+/cytokeratin20-/estrogen receptor+. The cause of rectal endometriosis in this case might have been related with previously received hormone replacement therapy for ovarian endometriosis. Following surgical removal of the lesion, this patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, although this kind of therapy is still controversial as to its effectiveness.

  4. Cyclical acute renal failure due to bilateral ureteral endometriosis.

    PubMed

    Akçay, A; Altun, B; Usalan, C; Ulusoy, S; Erdem, Y; Yasavul, U; Turgan, C; Caglar, S

    1999-09-01

    Endometriosis is a common disease but ureteral involvement is relatively rare. Ureteric endometriosis is mostly unilateral. Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. We present the cyclical acute renal failure associated with menstruation in a patient who developed severe bilateral ureteral obstruction due to endometriosis. Physicians should be aware of this uncommon but serious manifestation of endometriosis, especially if the clinical presentation is cyclical acute renal dysfunction in a premenopausal woman.

  5. Phthalates and risk of endometriosis

    PubMed Central

    Upson, Kristen; Sathyanarayana, Sheela; De Roos, Anneclaire J.; Thompson, Mary Lou; Scholes, Delia; Dills, Russell; Holt, Victoria L.

    2013-01-01

    Background Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. Objective To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. Methods We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. Results The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1–0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ΣDEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. Conclusions Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally

  6. MANAGEMENT OF ENDOMETRIOSIS IN TWO CAPTIVE MANDRILLS (MANDRILLUS SPHINX).

    PubMed

    Okeson, Danelle M; Higbie, Christine T; Mylniczenko, Natalie D; Haynes, April; Bennett, Suzanne; Klocke, Emily; Carpenter, James W

    2016-06-01

    Endometriosis has been reported in humans, great apes, and Old World monkeys. Although cases are noted anecdotally in Mandrillus spp., and a previously reported case was noted on postmortem examination, to the authors' knowledge, no previous reports of case management have been published in the peer-reviewed literature. This paper describes the medical and surgical management of endometriosis in two mandrills (Mandrillus sphinx).

  7. Early-life factors and endometriosis risk

    PubMed Central

    Upson, Kristen; Sathyanarayana, Sheela; Scholes, Delia; Holt, Victoria L.

    2015-01-01

    Objective To study early-life factors in relation to endometriosis risk in adulthood. Design Population-based case-control study. Setting Women’s Risk of Endometriosis (WREN) study was conducted among female enrollees ages 18-49 years of a large, integrated healthcare system in western Washington State. Patients Cases (n=310) were women diagnosed for the first time with endometriosis between years 1996-2001 and controls (n=727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population. Interventions None. Main outcome measures Adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother’s age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant’s mother or other family member. Results We observed that women who were regularly fed soy formula as infants had over twice the risk of endometriosis compared to unexposed women (aOR 2.4, 95% CI: 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI: 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI: 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null. Conclusion Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood. PMID:26211883

  8. Radiation-induced endometriosis in Macaca mulatta

    SciTech Connect

    Fanton, J.W.; Golden, J.G. )

    1991-05-01

    Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, and minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively.

  9. In Vitro and In Vivo Effects of Tumor Suppressor Gene PTEN on Endometriosis: An Experimental Study

    PubMed Central

    Lv, Juan; Zhu, Qiaoying; Jia, Xuemei; Yu, Ningzhu; Li, Qian

    2016-01-01

    Background Endometriosis can cause dysmenorrhea and infertility. Its pathogenesis has not yet been clarified and its treatment continues to pose enormous challenges. The protein tyrosine phosphatase (PTEN) gene is a tumor suppressor gene. The aim of this study was to investigate the role and significance of PTEN protein in the occurrence, development, and treatment of endometriosis through changes in apoptosis rate, cell cycle, and angiogenesis. Material/Methods PTEN was overexpressed and silenced in lentiviral vectors and inserted into primary endometrial cells. The changes in cell cycle and apoptosis in the different PTEN expression groups were evaluated using flow cytometry. Vessel growth mimicry was observed using 3-dimensional culture. A human-mouse chimeric endometriosis model was constructed using SCID mice. Hematoxylin and eosin staining and immunohistochemistry were used to detect pathological changes in ectopic endometrial tissues and the expression of VEGF protein in a human-mouse chimeric endometriosis mouse model. Results PTEN overexpression significantly increased apoptosis and inhibited the cell cycle compared with the silenced and control groups. Furthermore, cells expressing low PTEN levels were better able to undergo vasculogenic mimicry, and exhibited significantly increased angiogenesis compared to cells overexpressing PTEN. We found that ectopic foci were more easily formed in the endometrial tissue of SCID mice with low PTEN expression, and the VEGF expression in this group was relatively high. Conclusions PTEN inhibits the occurrence and development of endometriosis by regulating angiogenesis and the apoptosis and cell cycle of endometrial cells; therefore, we propose that the PTEN gene can be used to treat endometriosis. PMID:27744455

  10. [Endometriosis and surviving adolescence].

    PubMed

    Belaisch, J; Allart, J-P

    2006-03-01

    Endometriosis is a recurrent and painful disease which sometimes disturbs severely the quality of life of women who suffer from it. It is then logical to include a psychological back-up to its medical and surgical treatment. Nevertheless this support is not often offered to patients. One can hypothesize another and completely different way of seeing the problem: the mood swings and depression of endometriotic patients could possibly be, at least in some of them, the cause of the graft of endometrial cells and not the effect of pain and infertility. The mechanism of the development of endometriotic lesions could be related to a lowering of immune defences due to an alteration of the psycho-neuro-endocrino-immunologic network, resulting from difficult life experiences which mostly happen during adolescence. This concept may have beneficial effects for the patient whose case would be more understood in depth. But very few medical teams consider it worthwhile to include in their practices.

  11. Evaluation of Risk Factors Associated with Endometriosis in Infertile Women

    PubMed Central

    Ashrafi, Mahnaz; Sadatmahalleh, Shahideh Jahanian; Akhoond, Mohammad Reza; Talebi, Mehrak

    2016-01-01

    Background Endometriosis affects women’s physical and mental wellbeing. Symptoms include dyspareunia, dysmenorrhea, pelvic pain, and infertility. The purpose of this study is to assess the correlation between some relevant factors and symptoms and risk of an endometriosis diagnosis in infertile women. Materials and Methods A retrospective study of 1282 surgical patients in an infertility Institute, Iran between 2011 and 2013 were evaluated by laparoscopy. Of these, there were 341 infertile women with endometriosis (cases) and 332 infertile women with a normal pelvis (comparison group). Chi-square and t tests were used to compare these two groups. Logistic regression was done to build a prediction model for an endometriosis diagnosis. Results Gravidity [odds ratio (OR): 0.8, confidence interval (CI): 0.6-0.9, P=0.01], parity (OR: 0.7, CI: 0.6-0.9, P=0.01), family history of endometriosis (OR: 4.9, CI: 2.1-11.3, P<0.001), history of galactorrhea (OR: 2.3, CI: 1.5-3.5, P=0.01), history of pelvic surgery (OR: 1.9, CI: 1.3-2.7, P<0.001), and shorter menstrual cycle length (OR: 0.9, CI: 0.9-0.9, P=0.04) were associated with endometriosis. Duration of natural menstruation and age of menarche were not correlated with subsequent risk of endometriosis (P>0.05). Fatigue, diarrhea, constipation, dysmenorrhea, dyspareunia, pelvic pain and premenstrual spotting were more significant among late-stage endometriosis patients than in those with early-stage endometriosis and more prevalent among patients with endometriosis than that of the comparison group. In the logistic regression model, gravidity, family history of endometriosis, history of galactorrhea, history of pelvic surgery, dysmenorrhoea, pelvic pain, dysparaunia, premenstrual spotting, fatigue, and diarrhea were significantly associated with endometriosis. However, the number of pregnancies was negatively related to endometriosis. Conclusion Endometriosis is a considerable public health issue because it affects many

  12. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis.

    PubMed

    Chwalisz, Kristof; Perez, Maria Claudia; Demanno, Deborah; Winkel, Craig; Schubert, Gerd; Elger, Walter

    2005-05-01

    Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands. SPRMs exert clinically relevant tissue-selective progesterone agonist, antagonist, or mixed agonist/antagonist effects on various progesterone target tissues in vivo. Asoprisnil (J867) is the first SPRM to reach an advanced stage of clinical development for the treatment of symptomatic uterine fibroids and endometriosis. Asoprisnil belongs to the class of 11beta-benzaldoxime-substituted estratrienes that exhibit partial progesterone agonist/antagonist effects with high progesterone receptor specificity in animals and humans. Asoprisnil has no antiglucocorticoid activity in humans at therapeutic doses. It exhibits endometrial antiproliferative effects on the endometrium and breast in primates. Unlike progesterone antagonists, asoprisnil does not induce labor in relevant models of pregnancy and parturition. It induces amenorrhea primarily by targeting the endometrium. In human subjects with uterine fibroids, asoprisnil suppressed both the duration and intensity of uterine bleeding in a dose-dependent manner and reduced tumor volume in the absence of estrogen deprivation. In subjects with endometriosis, asoprisnil was effective in reducing nonmenstrual pain and dysmenorrhea. Asoprisnil may, therefore, provide a novel, tissue-selective approach to control endometriosis-related pain. SPRMs have the potential to become a novel treatment of uterine fibroids and endometriosis.

  13. Endometriosis-associated nerve fibers and pain

    PubMed Central

    Medina, Melissa G.; Lebovic, Dan I.

    2015-01-01

    The assessment and diagnosis of endometriosis remain elusive targets. Patient and medical-related factors add to delays in the detection and treatment. Recently, investigators have revealed specific nerve fibers present in endometriotic tissue, with existing parallels between density and pain severity. The aim of this review is to compile a comprehensive review of existing literature on endometriosis-related nerve fiber detection, and the effects of medical therapy on these neural fibers. We performed a systematic literature-based review using Medline and PubMed of nerve fibers detected in eutopic endometrium, endometriotic lesions, and the peritoneum. Various arrangements of significant medical terms and phrases consisting of endometriosis, pelvic pain, nerve fiber detection/density in endometriosis, and diagnoses methodology, including treatment and detection were applied in the search. Subsequent references used were cross-matched with existing sources to compile all additional similar reports. Similar nerve fibers were detected within lesions, endometrium, and myometrium, though at varying degrees of density. Hormonal therapy is widely used to treat endometriosis and was shown to be related to a reduction in fiber density. A direct result of specific nerve fiber detection within eutopic endometrial layers points to the use of a minimally invasive endometrial biopsy technique in reducing delay in diagnosis and subsequent possible preservation of fertility. PMID:19657753

  14. Endometriosis (For Teens)

    MedlinePlus

    ... has been diagnosed with endometriosis. There are several theories about how the endometrial tissue actually gets outside the uterus in the first place. One theory suggests that the menstrual blood flow somehow "backs ...

  15. Delivery after Operation for Deeply Infiltrating Endometriosis

    PubMed Central

    Allerstorfer, Christina; Enzelsberger, Simon H.; Shebl, Omar Josef; Mayer, Richard Bernhard

    2016-01-01

    Background. It has been suggested that, during pregnancy, endometriosis can cause a variety of disease-related complications. Objectives. The purpose of the study was to find out if women with histologically confirmed endometriosis do have a higher risk of adverse pregnancy outcome and if they suffer from a higher rate of complications during labor. Study Design. 51 women who underwent surgery because of deeply infiltrating endometriosis in the General Hospital Linz and the Women's General Hospital Linz and who gave birth in the Women's General Hospital Linz after the surgery were included in our survey. Results. 31 women (60.8%) had a spontaneous delivery and in 20 women (39.2%) a caesarean section was performed. There were no cases of third- and fourth-degree perineal lacerations. Collectively there were 4 cases (7.8%) of preterm delivery and one case (2.0%) of premature rupture of membranes. In two women (6.5%) a retained placenta was diagnosed. Conclusions. Our study is the first description on delivery modes after surgery for deeply infiltrating endometriosis. We did not find an elevated risk for perineal or vaginal laceration in women with a history of surgery for deeply infiltrating endometriosis, even when a resection of the rectum or of the posterior vaginal wall had been performed. PMID:27517050

  16. [Endometriosis. Potential mechanism of sterility. Management of patients with endometriosis. Review and reflections].

    PubMed

    Gómez Arzapalo, E; Gorozpe Calvillo, J I

    1999-02-01

    Endometriosis is an ailment which has no exact etiology due to its uncertain genesis, its inception can develop unnoticed, its silent evolution makes it difficult to identify it until a cardinal symptom appears and its semeiology provides us facts to integrate a diagnosis, it is an entity that does not have relation while and/or with the reproductive stage, neither with the parity, but we are aware it occurs in its different stages, varying from 9% to 33% in the reproductive cycle, it can be recurring after being medically or surgically treated, appearing endometriomas in it or in the infundibulum stump in the latter case. It is characterized by a collagenosis, endometrio abnormal implant out of the uterus cavity, thereby generating and inflammatory process in the zone of implant, increasing the cytokines production (polypeptide secreted by the lymphocytes and macrophages playing an important role in the immunological response), involving a dysfunction in the hypothalamus-pituitary-ovarian, altering the endocrinos physiology; regarding the genetic aspect, alterations in the chromosomes 4.9 in the Endometriosis frames have been found. The human semen preparation with half Ham F 10 enriched with ascorbic acid is described. In cases of permeable tubes or FIVTE.

  17. Pathogenetic Mechanisms of Deep Infiltrating Endometriosis.

    PubMed

    Tosti, Claudia; Pinzauti, Serena; Santulli, Pietro; Chapron, Charles; Petraglia, Felice

    2015-09-01

    Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest

  18. Levels of oestrogen receptor, progesterone receptor and αB-crystallin in eutopic endometrium in relation to pregnancy in women with endometriosis.

    PubMed

    Moberg, Christian; Bourlev, Vladimir; Ilyasova, Natalia; Olovsson, Matts

    2015-03-01

    Endometriosis affects fertility in many women and may partly be due to decreased endometrial receptivity. Several mechanisms have been suggested, notably, progesterone resistance for which a number of candidate biomarkers have been suggested. Here we demonstrate aberrant levels of steroid hormone receptors and the small heat shock protein αB-crystallin in eutopic endometrial epithelium from 38 women with peritoneal endometriosis diagnosed during investigation for secondary infertility. Spontaneous pregnancies within 1 year after medical and surgical treatment for endometriosis were recorded and semi-quantitative immunohistochemistry data compared between women with endometriosis who did or did not become pregnant and healthy controls. Stronger immunostaining for ER-α was detected in luminal and glandular endometrial epithelium from women with endometriosis who did not become pregnant during the post-treatment observation period versus endometriosis patients who became pregnant and controls. Staining levels of PR and PR-B were lower in patients without subsequent pregnancies than in the two other groups. Endometrial levels of αB-crystallin in endometriosis patients similar to those in controls were strongly correlated with the chance of becoming pregnant, whereas higher or lower levels were not.

  19. Immune interactions in endometriosis.

    PubMed

    Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G

    2011-09-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease.

  20. Endocannabinoid involvement in endometriosis

    PubMed Central

    Dmitrieva, Natalia; Nagabukuro, Hiroshi; Resuehr, David; Zhang, Guohua; McAllister, Stacy L.; McGinty, Kristina A.; Mackie, Ken; Berkley, Karen J.

    2010-01-01

    Endometriosis is a disease common in women that is defined by abnormal extrauteral growths of uterine endometrial tissue and associated with severe pain. Partly because how the abnormal growths become associated with pain is poorly understood, the pain is difficult to alleviate without resorting to hormones or surgery, which often produce intolerable side effects or fail to help. Recent studies in a rat model and women showed that sensory and sympathetic nerve fibers sprout branches to innervate the abnormal growths. This situation, together with knowledge that the endocannabinoid system is involved in uterine function and dysfunction and that exogenous cannabinoids were once used to alleviate endometriosis-associated pain, suggests that the endocannabinoid system is involved in both endometriosis and its associated pain. Here, using a rat model, we found that CB1 cannabinoid receptors are expressed on both the somata and fibers of both the sensory and sympathetic neurons that innervate endometriosis’s abnormal growths. We further found that CB1 receptor agonists decrease, whereas CB1 receptor antagonists increase, endometriosis-associated hyperalgesia. Together these findings suggest that the endocannabinoid system contributes to mechanisms underlying both the peripheral innervation of the abnormal growths and the pain associated with endometriosis, thereby providing a novel approach for the development of badly-needed new treatments. PMID:20833475

  1. Endometriosis in teenagers.

    PubMed

    Sarıdoğan, Ertan

    2015-08-01

    Endometriosis affects a significant proportion of teenagers. Published studies suggest that laparoscopically confirmed endometriosis could be found in over 60% of adolescent girls undergoing laparoscopic investigation for pain, in 75% of girls with chronic pelvic pain resistant to treatment and in 70% of girls with dysmenorrhea and in approximately 50% of girls with chronic pelvic pain not necessarily resistant to treatment. Both early and advanced forms, including deep endometriosis have been reported to be present in teenagers. It has recently been claimed that deep endometriosis has its roots in teenage years. Risk factors include obstructive mullerian anomalies, family history, early menarche and early onset dysmenorrhea. Both surgical and medical treatment approaches are used for treatment in this age group, but care should be taken when treatment with GnRHa and progestins is being considered due to their potential impact on bone formation. Further studies are urgently needed to determine whether early diagnosis and treatment of teenage endometriosis lead to better long term outcomes or simply increase number of interventions without preventing progression of the disease.

  2. Effects of early endometriosis on IVF-ET outcomes.

    PubMed

    Mekaru, Keiko; Yagi, Chiaki; Asato, Kozue; Masamoto, Hitoshi; Sakumoto, Kaoru; Aoki, Yoichi

    2013-01-01

    There have been very few reports on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with stage I/II endometriosis. The objective of this study was to investigate IVF-ET outcomes in women with early-stage endometriosis. We enrolled 35 women less than 40 years with unexplained infertility who underwent IVF-ET into the study. We compared 18 women with stage I/II endometriosis according to the revised American Society for Reproductive Medicine classification for endometriosis, who underwent 39 IVF-ET cycles (En (+) group) with 17 women without endometriosis who underwent 41 IVF-ET cycles (En (-) group). Higher requirements of total gonadotropin, a lower percentage of high-quality embryos of all fertilized eggs (9.0% vs. 16.3%), a relatively lower pregnancy rate (33.3% vs. 41.5%), and a lower live birth rate (25.6% vs. 34.1%) were observed in the En (+) group. Although no significant effect on IVF-ET outcome was observed, ovarian response may be decreased in women with stage I/II endometriosis. Considering the decreased number of high-quality embryos in the En (+) group, stage I/II endometriosis may have detrimental effects on embryo quality.

  3. Proton irradiation and endometriosis

    SciTech Connect

    Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.; Eason, R.L.; Boster, R.A.

    1983-08-01

    It was found that female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was determined to be 7 years after the proton exposure. The doses and energies of the radiation received by the experimental animals were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event. It is concluded that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crew members. 15 references.

  4. Proton irradiation and endometriosis

    SciTech Connect

    Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.; Eason, R.L.; Boster, R.A.

    1983-08-01

    Female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was 7 years after exposure. The doses and energies of the radiation received were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event, leading to the conclusion that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crewmembers.

  5. Lovastatin Reduces Stemness via Epigenetic Reprograming of BMP2 and GATA2 in Human Endometrium and Endometriosis

    PubMed Central

    Taghizadeh, Mahdieh; Noruzinia, Mehrdad

    2017-01-01

    Objective The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such as BMP2, GATA2 and RUNX2 as well as eMSCs markers. Materials and Methods In this experimental investigation, MSCs were isolated from endometrial and endometriotic tissues and treated with lovastatin and decitabin. To investigate the osteogenic and adipogenic differentiation of eMSCs treated with the different concentration of lovastatin and decitabin, BMP2, RUNX2 and GATA2 expressions were measured by real-time polymerase chain reaction (PCR). To determine involvement of DNA methylation in BMP2 and GATA2 gene regulations of eMSCs, we used quantitative Methylation Specific PCR (qMSP) for evaluation of the BMP2 promoter status and differentially methylated region of GATA2 exon 4. Results In the present study, treatment with lovastatin increased expression of BMP2 and RUNX2 and induced BMP2 promoter demethylation. We also demonstrated that lovastatin treatment down-regulated GATA2 expression via inducing methylation. In addition, the results indicated that CD146 cell marker was decreased to 53% in response to lovastatin treatment compared to untreated group. Conclusion These findings indicated that lovastatin treatment could increase the differentiation of eMSCs toward osteogenic and adiogenic lineages, while it decreased expression of eMSCs markers and subsequently reduced the stemness. PMID:28367417

  6. What Is Endometriosis?

    MedlinePlus

    ... Melissa McGaughey Melissa McGaughey , a 36-year-old grant writer in Milwaukee, Wis., began her journey with endometriosis when she was only 13. “Throughout high school and college, my pain got worse,” says McGaughey, ...

  7. Organochlorine pesticides and endometriosis.

    PubMed

    Cooney, Maureen A; Buck Louis, Germaine M; Hediger, Mary L; Vexler, Albert; Kostyniak, Paul J

    2010-11-01

    Limited study of persistent organochlorine pesticides (OCPs) and endometriosis has been conducted. One hundred women aged 18-40 years who were undergoing laparoscopy provided 20 cm(3) of blood for toxicologic analysis and surgeons completed operative reports regarding the presence of endometriosis. Gas chromatography with electron capture was used to quantify (ng/g serum) six OCPs. Logistic regression was utilized to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for individual pesticides and groups based on chemical structure adjusting for current cigarette smoking and lipids. The highest tertile of aromatic fungicide was associated with a fivefold risk of endometriosis (aOR=5.3; 95% CI, 1.2-23.6) compared to the lowest tertile. Similar results were found for t-nonachlor and HCB. These are the first such findings in a laproscopic cohort that suggest an association between OCP exposure and endometriosis. More prospective studies are necessary to ensure temporal ordering and confirm these findings.

  8. Chronic Pelvic Pain in Endometriosis: An Overview

    PubMed Central

    Triolo, Onofrio; Laganà, Antonio Simone; Sturlese, Emanuele

    2013-01-01

    Chronic pelvic pain (CPP) could be considered nowadays a deep health problem that challenges physicians all over the world. This because its aetiology is still unclear, the course of the disease could vary a lot among different patients and through time in the same patient, and the response to treatments is not every time successful. Among women who underwent laparoscopy for CPP, endometriosis is found in about 1/3 of the cases, while only 25% of women with histological confirmed endometriosis are asymptomatic. A wide range of variables may exert their influence on the resulting pain syndrome in endometriosis; for example, score according to American society for reproductive medicine (rASRM), size of the sub-peritoneal and pelvic wall implants, Douglas obliteration, previous surgery. It is widely accepted nowadays that central nervous system (CNS) and peripheral nervous system (PNS) seems to influence each other and this interconnection play a key role in pain modulation. Moreover, the phenomena induced by endometriosis in the pelvis, including the breakdown of peritoneal homeostasis and the induction of the production of proinflammatory and proangiogenic cytokines, are responsible of altered innervations and modulation of pain pathways in these patients. There are many proposed medical and surgical approach to treat this painful syndrome, although there is necessity of more efforts to create new non-invasive strategies that set a more accurate diagnosis of the causes of endometriotic-related CPP, and therefore facilitate its eradication. PMID:23671540

  9. Strategies for Management of Colorectal Endometriosis.

    PubMed

    Abrão, Mauricio Simões; Borrelli, Giuliano Moysés; Clarizia, Roberto; Kho, Rosanne Marie; Ceccaroni, Marcello

    2017-01-01

    Endometriosis has clearly three distinct clinical presentations and deep endometriosis, especially compromising the rectosigmoid is probably the most concerning one for both patients and surgeons. Currently, with the available tools, it is mandatory to have a precise diagnostic of this type of disease prior to indication of treatment. Strategies to manage this form of endometriosis will take into account several involved aspects, such as age of the patient, reproductive desire or infertility, clinical symptoms, as well as the extension and localization of the disease. Treatment could vary from more conservative to more radical depending on those aspects. As we pointed out in this article, the key to manage colorectal endometriosis is to start with a good diagnosis. Knowing exactly what is the extension and localization of the disease and knowing the patient's wishes as well as the clinical complaints, surgeons are able to define the best option for each patient. Critical points should always be discussed; for example, patients chosen to have clinical treatment should be aware of important issues regarding the follow-up, while patients undergoing surgery must be advised about all surgical possibilities and related complications.

  10. Pathogenesis and Pathophysiology of Endometriosis

    PubMed Central

    Burney, Richard O.; Giudice, Linda C.

    2013-01-01

    Originally described over three hundred years ago, endometriosis is classically defined by the presence of endometrial glands and stroma in extrauterine locations. Endometriosis is an inflammatory, estrogen dependent condition associated with pelvic pain and infertility. This work reviews the disease process from theories regarding origin to the molecular basis for disease sequelae. A thorough understanding of the histopathogenesis and pathophysiology of endometriosis is essential toward the development of novel diagnostic and treatment approaches for this debilitating condition. PMID:22819144

  11. Oxidation Sensitive Nociception Involved in Endometriosis Associated Pain

    PubMed Central

    Ray, Kristeena; Fahrmann, Johannes; Mitchell, Brenda; Paul, Dennis; King, Holly; Crain, Courtney; Cook, Carla; Golovko, Mikhail; Brose, Stephen; Golovko, Svetlana; Santanam, Nalini

    2015-01-01

    Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu, rich in inflammatory markers and pain-inducing prostaglandins PGE2/PGF2α and lipid peroxides, and the endometriotic tissue is innervated with nociceptors. Our clinical study showed the abundance of oxidatively-modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively-modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (i) the detection of lipoprotein derived oxidation-sensitive pain molecules, (ii) the ability of such molecules to induce nociception, and (iii) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins similar to that seen in the PF. The oxidatively-modified lipoproteins induced hypothermia (intra-cerebroventricular) in CD-1 mice and nociception in the Hargreaves paw-withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin-E and N-acetylcysteine and the NSAID, indomethacin suppressed the pain inducing ability of oxidatively-modified lipoproteins. Treatment of human endometrial cells with oxidatively-modified lipoproteins or PF from women with endometriosis showed up-regulation of similar genes belonging to the opioid and inflammatory pathways. Our finding that oxidatively-modified lipoproteins can induce nociception has a broader impact not only in the treatment of endometriosis-associated pain but also in other diseases associated with chronic pain. PMID:25599233

  12. Oxidation-sensitive nociception involved in endometriosis-associated pain.

    PubMed

    Ray, Kristeena; Fahrmann, Johannes; Mitchell, Brenda; Paul, Dennis; King, Holly; Crain, Courtney; Cook, Carla; Golovko, Mikhail; Brose, Stephen; Golovko, Svetlana; Santanam, Nalini

    2015-03-01

    Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu and is rich in inflammatory markers, pain-inducing prostaglandins prostaglandin E2 and prostaglandin F2α, and lipid peroxides; and the endometriotic tissue is innervated with nociceptors. Our clinical study showed that the abundance of oxidatively modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (1) the detection of lipoprotein-derived oxidation-sensitive pain molecules, (2) the ability of such molecules to induce nociception, and (3) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins to be similar to that seen in the PF. Oxidatively modified lipoproteins induced hypothermia (intracerebroventricular) in CD-1 mice and nociception in the Hargreaves paw withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin E and N-acetylcysteine, and the nonsteroidal anti-inflammatory drug indomethacin suppressed the pain-inducing ability of oxidatively modified lipoproteins. Treatment of human endometrial cells with oxidatively modified lipoproteins or PF from women with endometriosis showed upregulation of similar genes belonging to opioid and inflammatory pathways. Our finding that oxidatively modified lipoproteins can induce nociception has a broader impact not only on the treatment of endometriosis-associated pain but also on other diseases associated with chronic pain.

  13. Inflammasome as a Key Pathogenic Mechanism in Endometriosis.

    PubMed

    Bullón, Pedro; Navarro, Jose Manuel

    2016-07-08

    Endometriosis remains a challenging condition for clinicians to treat. To improve our results we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved. It is essential to understand the inflammatory reaction and immunity incorporating the new molecular concepts. Inflammasome has been described as a multiprotein complex and is considered a key regulator of the innate and adaptive host response that surveys the cytosol and other compartments into the cell. It is involved in the immediate detection and responds to the presence of danger- and pathogen-associated molecular patterns named DAMPs and PAMPs respectively, and has been described in several cells, mainly on immune cells of the myeloid lineage and epithelial cells in tissues with mucosal surfaces. Four inflammasome are formed in a stimulus-dependent manner of distinct composition. They are the Noll Like Receptors (NLR) proteins Nlrp1b, Nlrp3, Nlrc4, and Nlrp6, as well as the absent in melanoma 2 (AIM2). They activate the production of IL-1β and IL-18 that induce a host response such as pyroptosis, a proinflammatory cell death and the secretion of leaderless cytokines and growth factors. Inflammsome is linked to atherosclerosis, periodic fever syndromes, vitiligo, Crohn's disease, gout, asbestosis, silicosis, Alzheimer's disease and periodontitis. Endometriosis has been related with IL-1β and Another NLR, Nlrp7, was correlated with myometrial invasion in human endometrial cancer tissue. These new clues regarding the pathogenic mechanisms involving the inflammasome may be crucial in the future development for endometriosis therapy.

  14. Urine, peritoneal fluid and omental fat proteomes of reproductive age women: Endometriosis-related changes and associations with endocrine disrupting chemicals

    PubMed Central

    Williams, Katherine E.; Miroshnychenko, Olga; Johansen, Eric B.; Niles, Richard K.; Sundaram, Rajeshwari; Kannan, Kurunthachalam; Albertolle, Matthew; Zhou, Yan; Prasad, Namrata; Drake, Penelope M.; Giudice, Linda C.; Hall, Steven C.; Witkowska, H. Ewa; Louis, Germaine M. Buck; Fisher, Susan J.

    2015-01-01

    Endometriosis, ectopic growth of the uterine lining (endometrium), which affects 6–11% of reproductive age women, is associated with pelvic pain and infertility. We investigated the peritoneal fluid (PF), urine and omental fat (OF) proteomes of women with endometriosis vs. individuals with no surgically visualized endometriosis. All participants were enrolled in the NICHD-funded ENDO Study. A two-step proteomic study was performed. The first, a broad survey, employed a semi-quantitative gel LC-mass spectrometry (MS) workflow: SDS PAGE fractionation, trypsin digestion and LC–MS/MS. The results showed sample integrity but failed to detect any differences between women with and without endometriosis. The second step was a quantitative analysis of OF samples. We employed another sample set (n = 30) from women ± disease and isobaric mass-tag (iTRAQ) chemistry to label peptides and 2D LC–MS/MS for protein identification and quantification. Three proteins—matrix metalloproteinase-9, neutrophil elastase, and FAM49B—were significantly lower in abundance in samples from women with endometriosis. Interestingly, neutrophil elastase and FAM49B levels were associated with higher levels of a subset of endocrine disrupting chemicals (EDCs) that were previously measured in the same samples. The results of these experiments showed the feasibility of associating endometriosis with changes in the OF protein repertoire and EDC levels. Biological significance Endometriosis, pathological growth of the uterine lining, is associated with significant morbidities, including pain and infertility. However, the causes of this common condition are poorly understood. This study determined whether endometriosis was associated with changes in the protein composition of peritoneal fluid, urine and/or omental fat. A protein of unknown function (FAM49B) and two proteinases (metalloproteinase-9, neutrophil elastase) were down regulated in OF samples from women with versus without

  15. Progesterone resistance in endometriosis: link to failure to metabolize estradiol.

    PubMed

    Bulun, Serdar E; Cheng, You-Hong; Yin, Ping; Imir, Gonca; Utsunomiya, Hiroki; Attar, Erkut; Innes, Joy; Julie Kim, J

    2006-03-27

    Endometriosis is the most common cause of pelvic pain and affects an estimated 5 million women in the US. The biologically active estrogen estradiol (E2) is the best-defined mitogen for the growth and inflammation processes in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Progesterone and progestins may relieve pain by limiting growth and inflammation in endometriosis but a portion of patients with endometriosis and pelvic pain do not respond to treatment with progestins. Moreover, progesterone-induced molecular changes in the eutopic (intrauterine) endometrial tissue of women with endometriosis are either blunted or undetectable. These in vivo observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptors (PRs) and the lack of the PR isoform named progesterone receptor B (PR-B). In normal endometrium, progesterone acts on stromal cells to induce secretion of paracrine factor(s). These unknown factor(s) act on neighboring epithelial cells to induce the expression of the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD-2), which metabolizes the biologically active estrogen E2 to estrone (E1). In endometriotic tissue, progesterone does not induce epithelial 17beta-HSD-2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate 17beta-HSD-2 may be due to the lack of PR-B and very low levels of progesterone receptor A (PR-A) observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this local mitogen. The cellular and molecular mechanisms underlying progesterone resistance and failure to metabolize E2 in endometriosis are reviewed.

  16. Endometriosis and breast cancer: A survey of the epidemiological studies.

    PubMed

    Pontikaki, A; Sifakis, S; Spandidos, D A

    2016-01-01

    Endometriosis is a chronic gynecological disease with a wide spectrum of clinical manifestations that affects approximately 10% of women of reproductive age. Recent reviews have demonstrated the connection between endometriosis and breast cancer, which represents the most frequently diagnosed female cancer and the most common cause of cancer-related mortality among women worldwide. The aim of this study was to conduct a survey of available published epidemiological studies indicating the association between endometriosis and breast cancer, and simultaneously to categorize the results based on the strength of the association, with the intention of the critical evaluation of the existing data. We performed a rigorous search of the PubMed/Medline database, using the key words 'endometriosis' and 'breast cancer' for all studies published in the English language until September 2015. We found 4 retrospective cohort studies, 4 case-control studies and 3 case-cohort studies that demonstrated a notable risk for developing breast cancer among women with endometriosis. By contrast, we also found 5 case-control studies, 1 prospective cohort study, 1 case-cohort study and 1 cross-sectional study that demonstrated a negative association between endometriosis and breast cancer. In conclusion, as regards the clarification of a 'robust' or 'weak' association between endometriosis and breast cancer, no definite conclusions could be drawn, due to the limited number of studies and the limitations of each of these studies. New well-designed, prospective cohort or randomized control trials with long-term follow-up are warranted in order to provide evidence-based clinical recommendations for proper counseling, screening and treatment strategies for patients with endometriosis, and hence to improve public health.

  17. Endometriosis of episiotomy scar: a case report.

    PubMed

    Mihmanli, V; Ózkan, T; Genc, S; Cetinkaya, N; Uctas, H

    2015-01-01

    Endometriosis is characterized by the presence of histologically normal endometrial glands and stroma outside the uterine cavity. Endometriosis predominantly locates on peritoneal surfaces, but it also affects the vagina, vulva, and perineum, usually secondary to surgical or obstetric trauma. Endometriosis in an episiotomy scar is a fairly rare phenomenon. The authors present a case of endometriosis in an episiotomy scar.

  18. The role of inflammation and matrix metalloproteinases in equine endometriosis

    PubMed Central

    Benali, Silvia; Giannuzzi, Diana; Mantovani, Roberto; Castagnaro, Massimo; Falomo, Maria Elena

    2012-01-01

    Equine endometriosis is a multifactorial disease considered to be a major cause of equine infertility. The purpose of this study was to evaluate the reliability of histomorphological grading for biopsy-like samples compared to entire uterine wall samples, to examine the association between the degree of endometriosis with animal age, and to investigate the role of inflammation in endometriosis and the expression of different matrix metalloproteinases in equine endometrium. Histomorphological lesions in 35 uterine samples were examined while comparing biopsy-like samples and entire-wall samples. Seventeen uterine samples were stained with antibodies against MMP-2, MMP-9, MMP-14, and TIMP-2. The morphologic evaluation results of the biopsy-like tissue and entire-wall samples were significantly correlated. Endometriosis in older mares (>12 years of age) was more severe than in young mares (2~4 years of age), confirming the positive correlation between animal age and disease severity, while inflammation was poorly related to the degree of endometriosis. MMP-2 and MMP-14 were detected in stromal cells, while MMP-9 and TIMP-2 were both found in stromal and glandular epithelial cells. There were no significant differences in MMPs expression between the two groups (young vs. old mares). Additional studies on the activity of MMPs could further define the role of these enzymes in equine endometriosis. PMID:22705739

  19. Survivin and VEGF as Novel Biomarkers in Diagnosis of Endometriosis

    PubMed Central

    Vidakovic, Snezana; Milic, Natasa; Jeremic, Katarina; Markovic, Milos; Milosevic-Djeric, Ana; Lazovic-Radonjic, Gordana

    2016-01-01

    Summary Background The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis. Methods This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher’s, Student’s t-test or the Mann – Whitney test. Results There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF). Conclusions Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis. PMID:28356866

  20. Angiogenesis and Endometriosis

    PubMed Central

    Rocha, Ana Luiza L.; Reis, Fernando M.; Taylor, Robert N.

    2013-01-01

    A comprehensive review was performed to survey the role of angiogenesis in the pathogenesis of endometriosis. This is a multifactorial disease in which the development and maintenance of endometriotic implants depend on their invasive capacity and angiogenic potential. The peritoneal fluid of patients with endometriosis is a complex suspension carrying inflammatory cytokines, growth factors, steroid hormones, proangiogenic factors, macrophages, and endometrial and red blood cells. These cells and their signaling products concur to promote the spreading of new blood vessels at the endometriotic lesions and surroundings, which contributes to the endometriotic implant survival. Experimental studies of several antiangiogenic agents demonstrated the regression of endometriotic lesions by reducing their blood supply. Further studies are necessary before these novel agents can be introduced into clinical practice, in particular the establishment of the safety of anti-angiogenic medications in women who are seeking to become pregnant. PMID:23766765

  1. DNA methylation in endometriosis (Review)

    PubMed Central

    KOUKOURA, OURANIA; SIFAKIS, STAVROS; SPANDIDOS, DEMETRIOS A.

    2016-01-01

    Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis. PMID:26934855

  2. Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis

    PubMed Central

    2012-01-01

    Background In order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n = 18) suffering from moderate (stage 3; n = 8) or severe (stage 4; n = 10) ovarian endometriosis during proliferative (n = 13) and secretory (n = 5) phases of menstrual cycle was performed. Methods Individual pure RNA samples were subjected to Agilent’s Whole Human Genome 44K microarray experiments. Microarray data were validated (P < 0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n = 4/each) during proliferative and secretory (n = 4/each) phases. Results Higher clustering effect of pairing (cluster distance, cd = 0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd = 0.5) and phases of menstrual cycle (cd = 0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes

  3. Induction of Endometriosis in Mice: A New Model Sensitive to Estrogen

    EPA Science Inventory

    Endometriosis consists of the growth of endometrial tissue outside the uterus. A rat model of endometriosis is available to evaluate the potential for environmental chemicals to promote the disease but may he relatively insensitive for the evaluation of the hazard of certain comp...

  4. Jack in the box: inguinal endometriosis

    PubMed Central

    Pandey, Deeksha; Coondoo, Ambika; Shetty, Jyothi; Mathew, Stanley

    2015-01-01

    A 39-year-old woman with a left-sided inguinal swelling was referred to us with a diagnosis of inguinal hernia. On asking leading questions, the patient gave a typical history of cyclical pain and increased swelling during menstruation. Fine-needle aspiration biopsy revealed endometrial glands. Preoperatively, the extent of the endometriotic lesion was delineated using MRI. The lesion was approached through the patient's caesarean scar for cosmetic reasons and excised in toto. Final diagnosis was round ligament endometriosis. The patient was asymptomatic at 3, 6 and 12 months’ follow-up. This case re-emphasises the fact that endometriosis is an enigmatic disease and can be found anywhere in the body. Thus, a woman of reproductive age presenting with any cyclical symptom should be asked about its relation to her menstrual cycle. PMID:25827916

  5. Endometriosis in the Adolescent Patient.

    PubMed

    Stuparich, Mallory A; Donnellan, Nicole M; Sanfilippo, Joseph S

    2017-01-01

    The recognition and management of endometriosis in the adolescent patient is challenging. A strong clinical suspicion for endometriosis should be maintained in the adolescent who suffers from acyclic pelvic pain as well as absenteeism from school and lack of participation in daily activities. Risk factors include the presence of an obstructive Mullerian anomaly, a family history of endometriosis, and conditions that prolong exposure to endogenous and exogenous estrogens. Empiric medical therapy with nonsteroidal anti-inflammatory drugs and combined oral contraceptive pills may be considered in most adolescents with endometriosis. Failure of empiric therapy may warrant diagnostic laparoscopy, which affords a concomitant opportunity for treatment via excision of endometriosis. Endometriotic implants in the adolescent tend to be more atypical, appearing red/flame-like, clear/polypoid, or vesicular. Endometriosis tends to recur more often in adolescents when compared with adults, and the role of postoperative medical therapy for the suppression of disease progression is not entirely clear. Current knowledge on the impact of adolescent endometriosis on future fertility is limited but overall reassuring.

  6. Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

    PubMed Central

    Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J

    2008-01-01

    Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724

  7. Somatic Stem Cells and Their Dysfunction in Endometriosis

    PubMed Central

    Djokovic, Dusan; Calhaz-Jorge, Carlos

    2015-01-01

    Emerging evidence indicates that somatic stem cells (SSCs) of different types prominently contribute to endometrium-associated disorders such as endometriosis. We reviewed the pertinent studies available on PubMed, published in English language until December 2014 and focused on the involvement of SSCs in the pathogenesis of this common gynecological disease. A concise summary of the data obtained from in vitro experiments, animal models, and human tissue analyses provides insights into the SSC dysregulation in endometriotic lesions. In addition, a set of research results is presented supporting that SSC-targeting, in combination with hormonal therapy, may result in improved control of the disease, while a more in-depth characterization of endometriosis SSCs may contribute to the development of early-disease diagnostic tests with increased sensitivity and specificity. Key message: Seemingly essential for the establishment and progression of endometriotic lesions, dysregulated SSCs, and associated molecular alterations hold a promise as potential endometriosis markers and therapeutic targets. PMID:25593975

  8. Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis.

    PubMed

    Yu, Jie; Boicea, Anisoara; Barrett, Kara L; James, Christopher O; Bagchi, Indrani C; Bagchi, Milan K; Nezhat, Ceana; Sidell, Neil; Taylor, Robert N

    2014-03-01

    Accumulating evidence indicates that reduced fecundity associated with endometriosis reflects a failure of embryonic receptivity. Microdomains composed of endometrial gap junctions, which facilitate cell-cell communication, may be implicated. Pharmacological or genetic inhibition of connexin (Cx) 43 block human endometrial cell differentiation in vitro and conditional uterine deletion of Cx43 alleles cause implantation failure in mice. The aim of this study was to determine whether women with endometriosis have reduced eutopic endometrial Cx43. Cx26 acted as a control. Endometrial biopsies were collected from age, race and cycle phase-matched women without (15 controls) or with histologically confirmed endometriosis (15 cases). Immunohistochemistry confirmed a predominant localization of Cx43 in the endometrial stroma, whereas Cx26 was confined to the epithelium. Cx43 immunostaining was reduced in eutopic biopsies of endometriosis subjects and western blotting of tissue lysates confirmed lower Cx43 levels in endometriosis cases, with Cx43/β-actin ratios=.4±1.5 in control and =1.2±0.3 in endometriosis biopsies (P<0.01). When endometrial stromal cells (ESC) were isolated from endometriosis cases, Cx43 levels and scrape loading-dye transfer were reduced by ∼45% compared with ESC from controls. In vitro decidualization of ESC derived from endometriosis versus control subjects resulted in lesser epithelioid transformation and a significantly reduced up-regulation of Cx43 protein (1.2±0.2- versus 1.7±0.4-fold, P<0.01). No changes in Cx26 were observed. While basal steady-state levels of Cx43 mRNA did not differ with respect to controls, ESC from endometriosis cases failed to manifest a response to hormone treatment in vitro. In summary, eutopic endometrial Cx43 concentrations in endometriosis cases were <50% those of controls in vivo and in vitro, functional gap junctions were reduced and hormone-induced Cx43 mRNA levels were blunted.

  9. The Human Relations School.

    ERIC Educational Resources Information Center

    Fox, Robert S.; Lippitt, Ronald

    As an expansion of ED 026 320, the model for a Human Relations School sketched in this document is an attempt to answer these questions: What would it be like if a school were to see itself as a laboratory for living and learning in which the test that is known about human interaction were utilized? How would it be organized? What would be its…

  10. The eutopic endometrium in endometriosis: are the changes of clinical significance?

    PubMed

    Brosens, Ivo; Brosens, Jan J; Benagiano, Giuseppe

    2012-05-01

    The eutopic endometrium in women suffering from endometriosis is different in many ways from that of healthy controls. Both proliferative and secretory eutopic endometria exhibit changes in endometriosis with heterogeneous responses. In addition, nerve fibres appear in the endometrium and myometrium of these women. The endometrium is a rich source of pro-angiogenic factors and vascular events are often disrupted in endometriosis with an overall increase in angiogenesis. A number of investigations have shown that endometriosis is likely the most common cause of endometrial receptivity defects. Endometriosis is also associated with relative 17β-hydroxysteroid dehydrogenase type II deficiency and these molecular aberrations indicate that local oestrogen production sustains ectopic implants. Recently it has been shown that endometriosis, as a chronic inflammatory disorder, disrupts co-ordinated progesterone response throughout the reproductive tract, including the endometrium, leading to a condition of 'progesterone resistance'. Investigators have searched for biomarkers of endometriosis, but these investigations are fraught with methodological difficulties. In conclusion, molecular phenotyping of the endometrium is changing the disease paradigm, from being foremost an oestrogen-dependent disease to a disorder characterized primarily by progesterone resistance. In recent years, research on the pathogenesis of endometriosis has been focused on alterations in the uterus and particularly the eutopic endometrium. The eutopic endometrium in women suffering from endometriosis is different in many ways from that of healthy controls. Both proliferative and secretory eutopic endometria exhibit changes in endometriosis with heterogeneous responses. The endometrium is a rich source of pro-angiogenic factors and vascular events are often disrupted in endometriosis with an overall increase in angiogenesis. A number of investigations have shown that endometriosis is likely the most

  11. Lessons in Human Relations.

    ERIC Educational Resources Information Center

    Glenn, Joanne Lozar

    2003-01-01

    Explores the importance of relationship literacy--the ability to create good relationships with others--in the next economy and offers perspectives on how business education instructors can help students develop and improve their human relations skills for business success. (Author/JOW)

  12. Spontaneous hymeneal endometriosis: a rare cause of dyspareunia.

    PubMed

    Canlorbe, Geoffroy; Laas, Enora; Cortez, Annie; Daraï, Emile

    2014-03-26

    Vulvar endometriosis can occur after surgery or trauma and cause dyspareunia. A 30-year-old woman presented with orificial dyspareunia lasting for 5 months. Her history was marked by a vaginal birth without perineal injury and the removal of a cyst from the left Bartholin's gland. On examination, we observed a selectively painful, superficial and retractile lesion, 5 mm in diameter at the junction of the hymen at some distance from the bartholinitis scar. Endometriosis was suspected due to the exacerbation of pain during menses. The surgery consisted of excision of the hymenal area of the painful lesion. Pathological examination confirmed the presence of endometrial tissue. The painful symptoms resolved and no additional treatment was administered. Any vulvar lesion, regardless of its appearance and location, can be related to endometriosis. Surgical resection is recommended to relieve the symptoms and provide histological proof.

  13. Spontaneous hymeneal endometriosis: a rare cause of dyspareunia

    PubMed Central

    Canlorbe, Geoffroy; Laas, Enora; Cortez, Annie; Daraï, Emile

    2014-01-01

    Vulvar endometriosis can occur after surgery or trauma and cause dyspareunia. A 30-year-old woman presented with orificial dyspareunia lasting for 5 months. Her history was marked by a vaginal birth without perineal injury and the removal of a cyst from the left Bartholin’s gland. On examination, we observed a selectively painful, superficial and retractile lesion, 5 mm in diameter at the junction of the hymen at some distance from the bartholinitis scar. Endometriosis was suspected due to the exacerbation of pain during menses. The surgery consisted of excision of the hymenal area of the painful lesion. Pathological examination confirmed the presence of endometrial tissue. The painful symptoms resolved and no additional treatment was administered. Any vulvar lesion, regardless of its appearance and location, can be related to endometriosis. Surgical resection is recommended to relieve the symptoms and provide histological proof. PMID:24671316

  14. Anti-mullerian hormone is expressed by endometriosis tissues and induces cell cycle arrest and apoptosis in endometriosis cells

    PubMed Central

    2014-01-01

    Background The anti-mullerian hormone (AMH) is a member of the transforming growth factor β (TGF-β) superfamily, which is responsible of the regression of the mullerian duct. AMH is expressed in the normal endometrium, where, acting in a paracrine fashion, negatively regulates cellular viability. Our objective was to evaluate the in vitro effects of the treatment with AMH of endometriosic cells. Methods AMH expression in human endometriosis glands was evaluated by immunohistochemistry. RT-PCR has been used to quantify the expression levels of AMH and AMH RII isoforms, as well as of cytochrome P450 in both endometriosis epithelial and stromal cells Effects of AMH and AMH-cleaved treatment in endometriosis cells were evaluated by flow-cytometry analysis. Finally, it has been evaluated the effect of plasmin-digested AMH on cytochrome P450 activity. Results AMH and AMH RII isoforms, as well as cytochrome P450, were expressed in both endometriosis epithelial and stromal cells. Treatment of endometriosis stromal and epithelial cell growth with AMH was able to induce a decrease in the percentage of cells in S phase and increase percentage of cells in G1 and G2 phase; coherently, decreased cell viability and increased percentage of cells death fraction was observed. The plasmin-digested AMH was able to suppress most of the cytochrome P450 activity, causing an increase of pre-G1 phase and of apoptosis induction treating with plasmin-digested AMH in both cell lines, most marked in the epithelial cells. Conclusions The data produced suggest a possible use of AMH as therapeutic agents in endometriosis. PMID:24886254

  15. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis.

    PubMed

    Wu, Yan; Strawn, Estil; Basir, Zainab; Halverson, Gloria; Guo, Sun-Wei

    2006-01-01

    The physiological effects of progesterone (P) are mediated by two isoforms of progesterone receptors (PRs): PR-A and PR-B. Progestins have long been used in the treatment of endometriosis but unfortunately the relief of pain is relatively short-term. In addition, about nine percent of women with endometriosis simply do not respond to progestin therapy due to unknown reasons. In fact, a general tendency for relative progesterone resistance within eutopic and ectopic endometrium of women with endometriosis and also the downregulation of PR-B, but not PR-A, in endometriosis have been noted. Since promoter hypermethylation is well-documented to be associated with transcriptional silencing, we sought to determine the methylation status of the PR-A and PR-B promoter regions in the epithelial component of endometriotic implants using a combination of laser capture microdissection (LCM), methylation specific PCR, and bisulfite sequencing. We found that the promoter region of PR-B, but not PR-A, is hypermethylated in endometriosis as compared with controls. In addition, the PR-B expression was significantly reduced in the ectopic endometrium. Our finding suggests that progesterone resistance in endometriosis in general and the down regulation of PR-B, but not PR-A, in particular, are a result of promoter hypermethylation of PR-B, but not PR-A. This, in conjunction with our reported aberrant methylation of HOXA10 in the eutopic endometrium of women with endometriosis, strongly suggests that endometriosis is an epigenetic disease. This perspective should potentially open up new avenues for the delineation of pathogenesis of endometriosis, and might also lead to novel ways to treat the disease through reversing aberrant methylation via pharmacological means.

  16. Treatment of endometriosis in different ethnic populations: a meta-analysis of two clinical trials.

    PubMed

    Gerlinger, Christoph; Faustmann, Thomas; Hassall, Jeffrey J; Seitz, Christian

    2012-04-19

    Approaches to the treatment of endometriosis vary worldwide, but studies comparing endometriosis medications in different ethnic groups are rare. A systematic literature search identified two studies directly comparing dienogest (DNG) versus gonadotropin-releasing hormone (GnRH) analogues in European and Japanese populations. Meta-analysis of visual analogue scale scores revealed no heterogeneity in response between the trials, indicating equivalent efficacy of DNG and GnRH analogues for endometriosis-related pain across populations. DNG was significantly superior to GnRH analogues for bone mineral density change in both trials, but significant heterogeneity between the studies may indicate ethnic differences in physiology.

  17. Confronting Endometriosis | NIH MedlinePlus the Magazine

    MedlinePlus

    ... not even heard of: endometriosis. My endometriosis had advanced so much that it was wrapped around my abdomen. I have had four laparoscopic excision surgeries. My endometriosis isn’t gone, but it is ...

  18. Up-regulation of ribosome biogenesis by MIR196A2 genetic variation promotes endometriosis development and progression

    PubMed Central

    Yang, Ching-Wen; Chang, Hui-Wen; Lu, Cheng-Chan; Chen, Chih-Mei; Chan, Carmen; Chung, Ching; Tseng, Chun-Cheng; Hwang, Tritium; Sheu, Jim Jinn-Chyuan; Tsai, Fuu-Jen

    2016-01-01

    Aberrant miRNA expression has been reported in endometriosis and miRNA gene polymorphisms have been linked to cancer. Because certain ovarian cancers arise from endometriosis, we genotyped seven cancer-related miRNA single nucleotide polymorphisms (MiRSNPs) to investigate their possible roles in endometriosis. Genetic variants in MIR196A2 (rs11614913) and MIR100 (rs1834306) were found to be associated with endometriosis development and related clinical phenotypes, such as infertility and pain. Downstream analysis of the MIR196A2 risk allele revealed upregulation of rRNA editing and protein synthesis genes, suggesting hyper-activation of ribosome biogenesis as a driving force for endometriosis progression. Clinical studies confirmed higher levels of small nucleolar RNAs and ribosomal proteins in atypical endometriosis lesions, and this was more pronounced in the associated ovarian clear cell carcinomas. Treating ovarian clear cells with CX5461, an RNA polymerase I inhibitor, suppressed cell growth and mobility followed by cell cycle arrest at G2/M stage and apoptosis. Our study thus uncovered a novel tumorigenesis pathway triggered by the cancer-related MIR196A2 risk allele during endometriosis development and progression. We suggest that anti-RNA polymerase I therapy may be efficacious for treating endometriosis and associated malignancies. PMID:27741504

  19. Vulvar endometriosis and Nuck canal.

    PubMed

    Mazzeo, Carmelo; Gammeri, Emanuele; Foti, Agata; Rossitto, Maurizio; Cucinotta, Eugenio

    2014-12-29

    L’endometriosi è una patologia non ancora del tutto conosciuta che colpisce il 6-10% della popolazione femminile generare e il 35-50% della popolazione femminile affetta da dolore pelvico e infertilità. La sede più frequente di malattia è rappresentata dall’ovaio e ciò sostiene l’ipotesi patogenetica della mestruazione retrograda. Viene descritto un caso di non comune localizzazione vulvare di endometriosi riscontrata in una paziente precedentemente operata per una cisti di Nuck. La donna aveva notato da qualche mese l’insorgenza di una tumefazione nella regione vulvare che le causava dolore e dispareunia che si accentuavano nel periodo mestruale. Il sospetto clinico di endometriosi non aveva avuto conferma negli esami strumentali preoperatori che non avevano evidenziato alterazioni patognomoniche, nè differenze dei reperti in fase pre mestruale e mestruale. Solo l’esame istologico della neoformazione asportata ha confermato la diagnosi. Inoltre gli Autori con la presente nota desiderano sottolineare come nella patogenesi dell’endometriosi vulvare debba essere tenuta in considerazione la presenza della pervietà del dotto peritoneovaginale o dotto di Nuck. Nel caso clinico descritto, infatti, la paziente era stata sottoposta due anni prima ad asportazione di una cisti di Nuck con obliterazione del dotto peritoneovaginale. Tuttavia già in quella fase clinica poteva essersi determinato un impianto endometriosico, che si era poi evidenziato con la formazione del nodulo in sede vulvare asportato chirurgicamente.

  20. MRI atlas of ectopic endometriosis.

    PubMed

    Dallaudière, B; Salut, C; Hummel, V; Pouquet, M; Piver, P; Rouanet, J-P; Maubon, A

    2013-03-01

    Ectopic endometriosis is a common condition which is often underdiagnosed, where MRI can help make a diagnosis simply, non-invasively and without irradiation. However, imagery signs of it are enormously polymorphic with a wide range of possible locations. In this paper, we have tried to illustrate comprehensively all its MRI appearances depending on the different locations where it occurs.

  1. The experience of chronic illness in women: a comparison between women with endometriosis and women with chronic migraine headaches.

    PubMed

    Barnack, Jessica L; Chrisler, Joan C

    2007-01-01

    The diagnosis of a chronic illness is a life changing event that affects the biological, psychological, and sociological aspects of a person's life. The purpose of the present study was to compare the experiences of pain, physical and psychological well-being, stress, patient satisfaction, social support, and attitudes toward menstruation of women who suffer from endometriosis and women who suffer from chronic migraine headaches. It was hypothesized that women with endometriosis would have more negative scores than women who have migraines on all measures because endometriosis is not understood by society to be a valid source of pain. Participants were 41 women with endometriosis and 32 women with migraines who were recruited from support groups and online listservs. Women with endometriosis reported significantly more pain, stress, and negative attitudes toward menstruation than did women with migraines. Implications for the differential treatment of women with chronic illnesses related to the menstrual cycle are discussed.

  2. Innovations in classical hormonal targets for endometriosis.

    PubMed

    Pluchino, Nicola; Freschi, Letizia; Wenger, Jean-Marie; Streuli, Isabelle

    2016-01-01

    Endometriosis is a chronic disease of unknown etiology that affects approximately 10% of women in reproductive age. Several evidences show that endometriosis lesions are associated to hormonal imbalance, including estrogen synthesis, metabolism and responsiveness and progesterone resistance. These hormonal alterations influence the ability of endometrial cells to proliferate, migrate and to infiltrate the mesothelium, causing inflammation, pain and infertility. Hormonal imbalance in endometriosis represents also a target for treatment. We provide an overview on therapeutic strategies based on innovations of classical hormonal mechanisms involved in the development of endometriosis lesions. The development phase of new molecules targeting these pathways is also discussed. Endometriosis is a chronic disease involving young women and additional biological targets of estrogen and progesterone pharmacological manipulation (brain, bone and cardiovascular tissue) need to be carefully considered in order to improve and overcome current limits of long-term medical management of endometriosis.

  3. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis

    PubMed Central

    Ray, Amlan K.; DasMahapatra, Pramathes; Swarnakar, Snehasikta

    2016-01-01

    Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression. PMID:27695098

  4. A Pilot Study of the Prevalence of Leg Pain Among Women with Endometriosis

    PubMed Central

    Missmer, Stacey A.; Bove, Geoffrey M.

    2011-01-01

    Radiating leg pain is a common symptom presenting in manual therapy practices. Although this symptom has been reported as a complication of endometriosis, its prevalence and characteristics have not been studied. We surveyed members of a national endometriosis support group with endometriosis using a self-administered, mailed questionnaire. The main outcome measures were the prevalence and characteristics of leg pain. Of 94 respondents, leg pain was reported by 48 women (51%), and was bilateral in 59% of these symptomatic women. The likelihood of experiencing leg pain was related to weight gain since age 18, age, and height. The most common treatments tried included exercise, over-the-counter medications, and massage therapy, all with variable results. These data support leg pain as a prevalent complication of endometriosis, and that the disease may affect multiple peripheral nerves. Manual therapists should remain aware to this possible etiology for radiating pain. PMID:21665106

  5. A pilot study of the prevalence of leg pain among women with endometriosis.

    PubMed

    Missmer, Stacey A; Bove, Geoffrey M

    2011-07-01

    Radiating leg pain is a common symptom presenting in manual therapy practices. Although this symptom has been reported as a complication of endometriosis, its prevalence and characteristics have not been studied. We surveyed members of a national endometriosis support group with endometriosis using a self-administered, mailed questionnaire. The main outcome measures were the prevalence and characteristics of leg pain. Of 94 respondents, leg pain was reported by 48 women (51%), and was bilateral in 59% of these symptomatic women. The likelihood of experiencing leg pain was related to weight gain since age 18, age, and height. The most common treatments tried included exercise, over-the-counter medications, and massage therapy, all with variable results. These data support leg pain as a prevalent complication of endometriosis, and that the disease may affect multiple peripheral nerves. Manual therapists should remain aware to this possible etiology for radiating pain.

  6. Endometriosis: new concepts in the pathogenesis.

    PubMed

    Signorile, Pietro G; Baldi, Alfonso

    2010-06-01

    Endometriosis is a gynaecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Though there are several theories, research scientists remain unsure as to the definitive cause(s) of endometriosis. Considering the relevant health problems caused by endometriosis, all new information on the pathogenesis of this disease, may have important clinical implications. Goal of this article is to summarize the latest advances in the pathogenesis of endometriosis, with particular emphasis on the embryological theory, that has been recently re-proposed. The possible clinical implications of these findings will be discussed.

  7. Endometriosis: A Disease That Remains Enigmatic

    PubMed Central

    Velasco, Irene

    2013-01-01

    Endometriosis, a gynecologic pathology, is defined by the presence of a tissue similar to uterine endometrium, which is located in places other than physiologically appropriate. These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous, endogenous, or local hormonal stimuli. Endometriosis affects 8%–10% of women of reproductive age; in 30% of the women, the condition is associated with primary or secondary infertility. In several instances, endometriosis persists as a minimal or mild disease, or it can resolve on its own. Other cases of endometriosis show severe symptomatology that ends when menopause occurs. Endometriosis can, however, reactivate in several postmenopausal women when iatrogenic or endogenous hormones are present. Endometriosis is occasionally accompanied by malignant ovarian tumors, especially endometrioid and clear cell carcinomas. Its pathogenesis is widely debated, and its variable morphology appears to represent a continuum of individual presentations and progressions. Endometriosis has no pathognomonic signs or symptoms; it is therefore difficult to diagnose. Because of its enigmatic etiopathogenesis, there is currently no satisfactory therapy for all patients with endometriosis. Treatments include medications, surgery, or combined therapies; currently, the only procedures that seem to cure endometriosis are hysterectomy and bilateral salpingo-oophorectomy. In this paper, we review the most controversial and enigmatic aspects of this disease. PMID:23956867

  8. Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis

    PubMed Central

    Zhao, Yuechao; Gong, Ping; Chen, Yiru; Nwachukwu, Jerome C.; Srinivasan, Sathish; Ko, CheMyong; Bagchi, Milan K.; Taylor, Robert N.; Korach, Kenneth S.; Nettles, Kendall W.; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.

    2016-01-01

    Estrogenic and inflammatory components play key roles in a broad range of diseases including endometriosis, a common estrogen-dependent gynecological disorder in which endometrial tissue creates inflammatory lesions at extrauterine sites, causing pelvic pain and reduced fertility. Current medical therapies focus primarily on reducing systemic levels of estrogens, but these are of limited effectiveness and have considerable side effects. We developed estrogen receptor (ER) ligands, chloroindazole (CLI) and oxabicycloheptene sulfonate (OBHS), which showed strong ER-dependent anti-inflammatory activity in a preclinical model of endometriosis that recapitulates the estrogen dependence and inflammatory responses of the disease in immunocompetent mice and in primary human endometriotic stromal cells in culture. Estrogen-dependent phenomena, including cell proliferation, cyst formation, vascularization, and lesion growth, were all arrested by CLI or OBHS, which prevented lesion expansion and also elicited regression of established lesions, suppressed inflammation, angiogenesis, and neurogenesis in the lesions, and interrupted crosstalk between lesion cells and infiltrating macrophages. Studies in ERα or ERβ knockout mice indicated that ERα is the major mediator of OBHS effectiveness and ERβ is dominant in CLI actions, implying involvement of both ERs in endometriosis. Neither ligand altered estrous cycling or fertility at doses that were effective for suppression of endometriosis. Hence, CLI and OBHS are able to restrain endometriosis by dual suppression of the estrogen-inflammatory axis. Our findings suggest that these compounds have the desired characteristics of preventive and therapeutic agents for clinical endometriosis and possibly other estrogen-driven and inflammation-promoted disorders. PMID:25609169

  9. Estradiol promotes cells invasion by activating β-catenin signaling pathway in endometriosis

    PubMed Central

    Xiong, Wenqian; Zhang, Ling; Yu, Lan; Xie, Wei; Man, Yicun; Xiong, Yao; Liu, Hengwei; Liu, Yi

    2015-01-01

    Endometriosis is an estrogen-dependent disease that involves the adhesion, invasion, and angiogenesis of endometrial tissues outside of the uterine cavity. We hypothesized that a link exists between estrogen and beta-catenin (β-catenin) signaling in the pathogenesis of endometriosis. Human endometrial stromal cells (HESCs) were separated from eutopic endometrial tissues that were obtained from patients with endometriosis. β-catenin expression and cells invasiveness ability were up-regulated by 17β-estradiol (E2) in an estrogen receptor (ESR)-dependent manner, whereas β-catenin siRNA abrogated this phenomenon. Moreover, co-immunoprecipitation and dual immunofluorescence studies confirmed ESR1, β-catenin, and lymphoid enhancer factor 1/T cell factor 3 co-localization in the nucleus in HESCs after E2 treatment. To determine the role of β-catenin signaling in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium from endometriosis patients into ovariectomized severe combined immunodeficiency mice. The implantation of the endometrium was suppressed by β-catenin siRNA. Collectively, studies regarding β-catenin signaling are critical for improving our understanding of the pathogenesis of estrogen-induced endometriosis, which can translate into the development of treatments and therapeutic strategies for endometriosis. PMID:26432349

  10. Organochlorine Pesticides and Risk of Endometriosis: Findings from a Population-Based Case–Control Study

    PubMed Central

    De Roos, Anneclaire J.; Thompson, Mary Lou; Sathyanarayana, Sheela; Scholes, Delia; Barr, Dana Boyd; Holt, Victoria L.

    2013-01-01

    Background: Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. Objective: We investigated endometriosis risk in relation to environmental exposure to OCPs. Methods: We conducted the present analyses using data from the Women’s Risk of Endometriosis (WREN) study, a population-based case–control study of endometriosis conducted among 18- to 49-year-old female enrollees of a large health care system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n = 248) first diagnosed between 1996 and 2001 and from population-based controls (n = 538). We estimated odds ratios (OR) and 95% CIs using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Results: Our data suggested increased endometriosis risk associated with serum concentrations of β-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0, 2.2). The association between serum β-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR = 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR = 2.5; 95% CI: 1.1, 5.3). Conclusions: In our case–control study of women enrolled in a large health care system in the U.S. Pacific Northwest, serum concentrations of β-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may affect the health of reproductive-age women. Citation: Upson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, Holt VL. 2013

  11. Endometriosis of Extra-Abdominal Soft Tissues: A Tertiary Center Experience.

    PubMed

    Wang, Jayson; Strauss, Dirk C; Messiou, Christina; Thway, Khin

    2016-09-01

    While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens.

  12. Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain

    PubMed Central

    As-Sanie, Sawsan; Kim, Jieun; Schmidt-Wilcke, Tobias; Sundgren, Pia C.; Clauw, Daniel J.; Napadow, Vitaly; Harris, Richard E.

    2015-01-01

    In contrast to women with relatively asymptomatic endometriosis, women with endometriosis-associated chronic pelvic pain (CPP) exhibit non-pelvic hyperalgesia and decreased gray matter volume in key neural pain processing regions. While these findings suggest central pain amplification in endometriosis-associated CPP, the underlying changes in brain chemistry and function associated with central pain amplification remain unknown. We performed proton spectroscopy and seed-based resting functional connectivity MRI to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions. Relative to age-matched pain-free controls, women with endometriosis-associated CPP displayed elevated levels of combined glutamine-glutamate (Glx) within the anterior insula, and greater anterior insula connectivity to the medial prefrontal cortex (mPFC). Increased connectivity between these regions was positively correlated with anterior insula Glx concentrations (r=0.87), as well as clinical anxiety (r=0.61,p=0.02), depression (r=0.60,p=0.03), and pain intensity (r=0.55,p=0.05). There were no significant differences in insula metabolite levels or resting-state connectivity in endometriosis without CPP subjects versus controls. We conclude that enhanced anterior insula glutamatergic neurotransmission and connectivity with the mPFC, key regions of the salience and default mode networks, may play a role in the pathophysiology of CPP independent of the presence of endometriosis. PMID:26456676

  13. Graves Disease Is Associated With Endometriosis

    PubMed Central

    Yuk, Jin-Sung; Park, Eun-Ju; Seo, Yong-Soo; Kim, Hee Jin; Kwon, Seon-Young; Park, Won I.

    2016-01-01

    Abstract The aim of this cross-sectional study was to compare the prevalence of thyroid diseases between women with and without endometriosis. We established the endometriosis group according to diagnosis codes, surgery codes, and gonadotropin-releasing hormone agonist codes using the Korean Health Insurance Review and Assessment Service—National Inpatients Sample (HIRA-NIS) from 2009 to 2011. Four controls were randomly matched to each endometriosis case. Thyroid disease cases were selected using the thyroid disease diagnosis code (E0X). Among the 1,843,451 women sampled, 5615 had endometriosis; 22,460 controls were matched to the endometriosis cases. After adjustment for age and sampling year, Graves disease was associated with endometriosis (odds ratio [OR]: 2.52; 95% CI: 1.30–4.88; P < 0.01), while hypothyroidism was not (OR: 1.17; 95% CI: 0.90–1.52; P = 0.25). Autoimmune hypothyroidism was also not associated with endometriosis (OR: 1.61; 95% CI: 0.88–2.94; P = 0.12). This study revealed an association between Graves disease and endometriosis. PMID:26962803

  14. Pathophysiology and Immune Dysfunction in Endometriosis.

    PubMed

    Ahn, Soo Hyun; Monsanto, Stephany P; Miller, Caragh; Singh, Sukhbir S; Thomas, Richard; Tayade, Chandrakant

    2015-01-01

    Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis.

  15. The progesterone receptor coactivator Hic-5 is involved in the pathophysiology of endometriosis.

    PubMed

    Aghajanova, Lusine; Velarde, Michael C; Giudice, Linda C

    2009-08-01

    Endometriosis is an estrogen-dependent disorder primarily associated with pelvic pain and infertility in up to 10% of women of reproductive age. Recent studies suggest that resistance to progesterone action may contribute to the development and pathophysiology of this disorder. In this study we examined the in vivo and in vitro expression and function of one progesterone receptor (PR) coactivator, Hic-5, in human endometrium and endometrial stromal fibroblasts (hESFs) from 29 women with and 30 (control) women without endometriosis. Hic-5 was highly expressed in stromal, but not epithelial, cells in women without endometriosis, in a cycle-dependent manner. In contrast, Hic-5 expression was not regulated during the menstrual cycle in hESFs from women with endometriosis and was significantly reduced in hESFs from women with vs. without disease. Hic-5 mRNA expression throughout the cycle in endometrium from control women, but not those with endometriosis, correlated with expression of PR. Hic-5 mRNA in hESFs was significantly up-regulated in control but not endometriosis hESFs after treatment in vitro with 8-bromoadenosine-cAMP for 96 h but only modestly after 14 d of progesterone treatment. Hic-5 silencing did not influence cAMP-regulated gene expression but affected genes regulated solely by progesterone (e.g. DKK1 and calcitonin). Together the data suggest that the proposed progesterone resistance in endometrium from women with endometriosis derives, in part, from impaired expression of the PR coactivator, Hic-5, in endometrial tissue and cultured endometrial stromal fibroblasts.

  16. Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis

    PubMed Central

    Sugihara, K.; Kobayashi, Y.; Suzuki, A.; Tamura, N.; Motamedchaboki, K.; Huang, C.-T.; Akama, T.O.; Pecotte, J.; Frost, P.; Bauer, C.; Jimenez, J.B.; Nakayama, J.; Aoki, D.; Fukuda, M.N.

    2014-01-01

    Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans. PMID:25047118

  17. Priorities for endometriosis research: a proposed focus on deep dyspareunia.

    PubMed

    Vercellini, Paolo; Meana, Marta; Hummelshoj, Lone; Somigliana, Edgardo; Viganò, Paola; Fedele, Luigi

    2011-02-01

    Women with endometriosis have a substantial increase in risk of deep dyspareunia with respect to the general female population of corresponding age. This symptom has personal and intimate implications, including unfavorable emotional impact in partners. Deep dyspareunia caused by endometriosis can be viewed as an originally visceral type of pain secondary to chronic inflammation (nociception) but with several superimposed components, including hyperalgesia, abnormal cortical perception, and psychological factors. Therefore, a simplistic biometric approach does not allow a comprehensive and elaborated assessment of the global impact of the symptom on women's sexual function, psychological well-being, body-image, self-esteem, and relational adjustment. We suggest 10 specific issues to be addressed in future research on a clinically as well as scientifically neglected aspect of female health. Time has come to address this physically and psychologically distressing affliction without embarrassment and with a decidedly multidisciplinary perspective.

  18. Serum miR-451a Levels Are Significantly Elevated in Women With Endometriosis and Recapitulated in Baboons (Papio anubis) With Experimentally-Induced Disease.

    PubMed

    Nothnick, Warren B; Falcone, Tommaso; Joshi, Niraj; Fazleabas, Asgerally T; Graham, Amanda

    2016-12-05

    We have previously demonstrated that human microRNA-451a (miR-451a) endometriotic lesion expression is significantly higher compared to that of the corresponding eutopic endometrium. The objective of the current study was to examine the relationship between lesion and serum content of miR-451a and to determine the utility of serum miR-451a in distinguishing between women with and without visible signs of endometriosis. Eighty-one participants were enrolled in this study, 41 with confirmed endometriosis and 40 without visible signs of endometriosis at laparoscopy (n = 20) or symptoms of endometriosis (pain, infertility n = 20). Experimental endometriosis was also induced in 8 baboons. Blood, endometriotic lesions, and eutopic endometrial samples were collected from women undergoing laparoscopy for surgical removal of endometriosis. Blood was also collected from control participants with no signs and symptoms associated with the disease as well as from baboons prior to, and then 1, 3, 6, 9, and 15 months postinduction of endometriosis. MicroRNA-451a was assessed by quantitative real-time polymerase chain reaction in all samples. In humans, serum miR-451a levels positively correlated with endometriotic lesion miR-451a content, and sera levels were significantly higher in these participants compared to controls. The area under the curve (AUC) for miR-451a was 0.8599. In baboons, serum miR-451a reached statistically significant peak levels at 6 months postinduction of endometriosis. We conclude from this study that sera miR-451a levels positively correlated with endometriotic lesion content and are significantly greater compared to sera levels in women without visible signs or symptoms of endometriosis. MicroRNA-451a may serve as a serum diagnostic marker for endometriosis.

  19. Deep endometriosis of the colon.

    PubMed

    Ropacka-Lesiak, Mariola; Świder-Musielak, Joanna; Wójcicka, Małgorzata; Łyczywek, Anna; Skrzypek, Maciej; Waliszewski, Wojciech

    2013-01-01

    The article presents a case of deep intestinal endometriosis in a 27-year-old woman who complained of dysmenorrhea and infertility. The diagnostic process included ultrasonography as well as colonoscopy, barium enema and CT imaging. Because of the presence of two distant changes which involved nearly the full thickness of the rectal wall and the major part of its circumference, the decision to perform an anterior rectal resection with a simultaneous retroperitoneal colorectostomy was made. The Knight technique was implemented. The surgery involved the anterior rectal resection, the transverse rectal stump closure by use of a stapling device (TA50), and the creation of colorectal circular anastomosis with the CEEA 31 stapler.

  20. Physical activity and endometriosis risk in women with infertility or pain

    PubMed Central

    Ricci, Elena; Viganò, Paola; Cipriani, Sonia; Chiaffarino, Francesca; Bianchi, Stefano; Rebonato, Giorgia; Parazzini, Fabio

    2016-01-01

    Abstract Background: The potential association between endometriosis and physical activity (PA) has been suggested in several epidemiological studies. We aimed to establish whether PA influences endometriosis risk. Methods: MEDLINE and EMBASE were searched using “physical activity” OR “exercise” combined with “endometriosis,” in Medical Subject Headings and free text. We selected original articles in English, published up to April 2016, evaluating the association between endometriosis and recent or past PA (case–control or cohort studies). References of retrieved papers were reviewed. We computed summary odds ratios (ORs) of endometriosis for recent and past PA. Results: Six case–control and 3 cohort studies included 3355 cases for recent PA and 4600 cases for past PA. The summary OR for endometriosis according to PA level, calculated by the random-effect model, was 0.85 [95% confidence interval (CI) 0.67–1.07] for any recent versus no PA. As compared to no recent PA, ORs for low and moderate/high PA were 1.00 (95% CI: 0.68–1.28) and 0.75 (95% CI: 0.53–1.07), respectively. Conclusions: Though it suggests that PA may reduce the risk of endometriosis, this meta-analysis does not conclusively support the hypothesis. Whether our findings are really explained by the benefit of exercise at molecular and endocrine level, or related to confounding mechanisms, such as study design, choice of controls, and PA potentially improving pain, needs to be further investigated. PMID:27749551

  1. Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro.

    PubMed

    Tariverdian, Nadja; Rücke, Mirjam; Szekeres-Bartho, Julia; Blois, Sandra M; Karpf, Eva F; Sedlmayr, Peter; Klapp, Burghard F; Kentenich, Heribert; Siedentopf, Friederike; Arck, Petra C

    2010-03-01

    Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n = 69). Within this cohort, early stage of endometriosis were diagnosed in n = 30 and advanced stage of endometriosis in n = 8. Levels of progesterone in serum were determined. Frequency of progesterone receptor (PR) expression on CD56(+) and CD8(+) peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the progesterone derivative dydrogesterone, or both, were evaluated. Furthermore, the production of progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56(+)PR(+) and CD8(+)PR(+) peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH

  2. Human Relations Class. A Syllabus.

    ERIC Educational Resources Information Center

    Guillen, Mary A.

    A junior high level human relations class develops human interaction and oral communication skills. A week-by-week syllabus contains the following components: introduction of the students to each other and to the principles of body language, transactional analysis, and group interaction; behavior contracts; group dynamics topics and exercises;…

  3. [Hypothetical link between endometriosis and xenobiotics-associated genetically modified food].

    PubMed

    Aris, A; Paris, K

    2010-12-01

    Endometriosis is an oestrogen-dependent inflammatory disease affecting 10 % of reproductive-aged women. Often accompanied by chronic pelvic pain and infertility, endometriosis rigorously interferes with women's quality of life. Although the pathophysiology of endometriosis remains unclear, a growing body of evidence points to the implication of environmental toxicants. Over the last decade, an increase in the incidence of endometriosis has been reported and coincides with the introduction of genetically modified foods in our diet. Even though assessments of genetically modified food risk have not indicated any hazard on human health, xenobiotics-associated genetically modified food, such as pesticides residues and xenoproteins, could be harmful in the long-term. The "low-dose hypothesis", accumulation and biotransformation of pesticides-associated genetically modified food and the multiplied toxicity of pesticides-formulation adjuvants support this hypothesis. This review summarizes toxic effects (in vitro and on animal models) of some xenobiotics-associated genetically modified food, such as glyphosate and Cry1Ab protein, and extrapolates on their potential role in the pathophysiology of endometriosis. Their roles as immune toxicants, pro-oxidants, endocrine disruptors and epigenetic modulators are discussed.

  4. Ecto-nucleotidases Activities in the Contents of Ovarian Endometriomas: Potential Biomarkers of Endometriosis

    PubMed Central

    Texidó, Laura; Romero, Claudia; García-Valero, José; Fernández Montoli, M. Eulalia; Baixeras, Núria; Condom, Enric; Ponce, Jordi; García-Tejedor, Amparo; Martín-Satué, Mireia

    2014-01-01

    Endometriosis, defined as the growth of endometrial tissue outside the uterus, is a common gynecologic condition affecting millions of women worldwide. It is an inflammatory, estrogen-dependent complex disorder, with broad symptomatic variability, pelvic pain, and infertility being the main characteristics. Ovarian endometriomas are frequently developed in women with endometriosis. Late diagnosis is one of the main problems of endometriosis; thus, it is important to identify biomarkers for early diagnosis. The aim of the present work is to evaluate the ecto-nucleotidases activities in the contents of endometriomas. These enzymes, through the regulation of extracellular ATP and adenosine levels, are key enzymes in inflammatory processes, and their expression has been previously characterized in human endometrium. To achieve our objective, the echo-guided aspirated fluids of endometriomas were analyzed by evaluating the ecto-nucleotidases activities and compared with simple cysts. Our results show that enzyme activities are quantifiable in the ovarian cysts aspirates and that endometriomas show significantly higher ecto-nucleotidases activities than simple cysts (5.5-fold increase for ATPase and 20-fold for ADPase), thus being possible candidates for new endometriosis biomarkers. Moreover, we demonstrate the presence of ecto-nucleotidases bearing exosomes in these fluids. These results add up to the knowledge of the physiopathologic mechanisms underlying endometriosis and, open up a promising new field of study. PMID:25276049

  5. International Conference on Human Relations.

    DTIC Science & Technology

    2007-11-02

    Festinger , Sherif, Ex, Rohrer, Pinto, Singh, and Mailhiot. One outcome of the Conference was the formation of a working committee to establish an International Documentation and Information Center for the field of Human Relations.

  6. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    PubMed Central

    Roy, Deodutta; Morgan, Marisa; Yoo, Changwon; Deoraj, Alok; Roy, Sandhya; Yadav, Vijay Kumar; Garoub, Mohannad; Assaggaf, Hamza; Doke, Mayur

    2015-01-01

    We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK) signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors. PMID:26512648

  7. CRISPLD2 is a target of progesterone receptor and its expression is decreased in women with endometriosis.

    PubMed

    Yoo, Jung-Yoon; Shin, Heesung; Kim, Tae Hoon; Choi, Won-Seok; Ferguson, Susan D; Fazleabas, Asgerally T; Young, Steven L; Lessey, Bruce A; Ha, Un-Hwan; Jeong, Jae-Wook

    2014-01-01

    Endometriosis, defined as the presence of endometrial cells outside of the uterine cavity, is a major cause of infertility and pelvic pain, afflicting more than 10% of reproductive age women. Endometriosis is a chronic inflammatory disease and lipopolysaccharide promotes the proliferation and invasion of endometriotic stromal cells. Cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) has high affinity for lipopolysaccharide and plays a critical role in defense against endotoxin shock. However, the function of CRISPLD2 has not been studied in endometriosis and uterine biology. Herein, we examined the expression of CRISPLD2 in endometrium from patients with and without endometriosis using immunohistochemistry. The expression of CRISPLD2 was higher in the secretory phase in human menstrual cycle compared to proliferative phase. The expression of CRISPLD2 was significantly decreased in the endometrium of women with endometriosis in the early secretory phase compared to women without endometriosis. The increase of CRISPLD2 expression at the early secretory and dysregulation of its expression in endometriosis suggest progesterone (P4) regulation of CRISPLD2. To investigate whether CRISPLD2 is regulated by P4, we examined the expression of the CRISPLD2 in the uteri of wild-type and progesterone receptor knock out (PRKO) mice. The expression of CRISPLD2 was significantly increased after P4 treatment in the wild-type mice. However, CRISPLD2 expression was significantly decreased in the (PRKO) mice treated with P4. During early pregnancy, the expression of CRISPLD2 was increased in decidua of implantation and post-implantation stages. CRISPLD2 levels were also increased in cultured human endometrial stromal cells during in vitro decidualization. These results suggest that the CRISPLD2 is a target of the progesterone receptor and may play an important role in pathogenesis of endometriosis.

  8. Limited value of pro-inflammatory oxylipins and cytokines as circulating biomarkers in endometriosis – a targeted ‘omics study

    PubMed Central

    Lee, Yie Hou; Cui, Liang; Fang, Jinling; Chern, Bernard Su Min; Tan, Heng Hao; Chan, Jerry K. Y.

    2016-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (−50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (−39%, −54% and −76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis. PMID:27193963

  9. Endometriosis: translation of molecular insights to management.

    PubMed

    Langan, K L; Farrell, M E; Keyser, E A; Salyer, B A; Burney, R O

    2014-09-01

    Endometriosis is a debilitating gynecologic disorder causing pelvic pain and infertility and characterized by the implantation of endometrial tissue to extrauterine locations. Though aspects of the condition remain enigmatic, the molecular pathophysiology of endometriosis appears to be clarifying. Estrogen dependence of the disease is a sentinel endocrine feature and reduction of estrogen bioavailability is the therapeutic principle upon which traditional treatment and prevention approaches have been based. Endometriosis is a chronic inflammatory condition associated with lesional neoangiogenesis and attenuated progesterone action at the level of the endometrium. The elucidation of the molecular pathways mediating these observations has revealed new targets for directed medical and surgical treatment. This paper will review current approaches to the management of endometriosis in the context of the molecular pathophysiology.

  10. Spontaneous endometriosis in an umbilical skin lesion.

    PubMed

    Chatzikokkinou, Paraskevi; Thorfinn, Johan; Angelidis, Ioannis K; Papa, Giovanni; Trevisan, Giusto

    2009-09-01

    Cutaneous endometriosis of the umbilicus is an unusual condition with unclear pathogenetic mechanisms that might be mistaken for a malignant condition. A 46-year-old woman presented with a cutaneous black mass in the umbilicus. The lesion was removed surgically and histological analyses revealed that it consisted of endometrial tissue. There was no recurrence at 18-month follow-up. Endometriosis of the umbilicus is a rare condition and the pathogenesis is not completely elucidated. According to one theory, intraperitoneal endometrial tissue is translocated during endoscopic surgery or other surgical procedures that involve the umbilicus. However, in this case there was no history of abdominal wall surgery. We conclude that endometriosis is important to consider in cases of unclear skin lesions of the umbilicus, even in cases with no previous abdominal surgery. Moreover, umbilical endometriosis of the skin can have different appearances that resemble malignant tumors, and radical surgery with histology is therefore indicated.

  11. How Do Health Care Providers Diagnose Endometriosis?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose endometriosis? Skip sharing on social media ... under a microscope, to confirm the diagnosis. 1 Health care providers may also use imaging methods to produce ...

  12. What Are the Symptoms of Endometriosis?

    MedlinePlus

    ... in the intestine or lower abdomen Painful bowel movements or painful urination during menstrual periods Heavy menstrual periods Premenstrual spotting or bleeding between periods In addition, women who are diagnosed with endometriosis may have painful ...

  13. Pathophysiology of cyclic hemorrhagic ascites and endometriosis.

    PubMed

    Ussia, Anastasia; Betsas, George; Corona, Roberta; De Cicco, Carlo; Koninckx, Philippe R

    2008-01-01

    Massive hemorrhagic ascites (4470 mL, range 1-10 L) in women with endometriosis is a rare condition occurring predominantly in black women. Of the 43 case reports published, 42 are compatible with the hypothesis that the hemorrhagic ascites is predominantly a consequence of excessive ovarian transudation similar to a Meigs syndrome. Indeed, bilateral ovariectomy cures the condition without recurrences, whereas after unilateral ovariectomy or cystectomy recurrence rate is more than 50%; during ovarian suppression by luteinizing hormone-releasing hormone agonist ascites disappears, but reappears after treatment. Superficial pelvic endometriosis also contributes to the ascites because after superficial endometriosis destruction the recurrence rate is only 4 in 14. Based on these data, it is suggested, to scrutinize the ovaries for tumors given the analogy with Meigs syndrome. In women desiring fertility, conservative treatment with destruction of endometriosis only can be attempted given the cure rate of some 20%. It is unknown what the effect of ovulation induction would be.

  14. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis.

    PubMed

    Arosh, Joe A; Lee, JeHoon; Balasubbramanian, Dakshnapriya; Stanley, Jone A; Long, Charles R; Meagher, Mary W; Osteen, Kevin G; Bruner-Tran, Kaylon L; Burghardt, Robert C; Starzinski-Powitz, Anna; Banu, Sakhila K

    2015-08-04

    Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis.

  15. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

    PubMed Central

    Arosh, Joe A.; Lee, JeHoon; Balasubbramanian, Dakshnapriya; Stanley, Jone A.; Long, Charles R.; Meagher, Mary W.; Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Burghardt, Robert C.; Starzinski-Powitz, Anna; Banu, Sakhila K.

    2015-01-01

    Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis. PMID:26199416

  16. Defining Future Directions for Endometriosis Research

    PubMed Central

    D’Hooghe, Thomas M.; Fazleabas, Asgerally; Giudice, Linda C.; Montgomery, Grant W.; Petraglia, Felice; Taylor, Robert N.

    2013-01-01

    Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.1 A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:23427182

  17. A call for more transparency of registered clinical trials on endometriosis

    PubMed Central

    Guo, Sun-Wei; Hummelshoj, Lone; Olive, David L.; Bulun, Serdar E.; D'Hooghe, Thomas M.; Evers, Johannes L.H.

    2009-01-01

    In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis. PMID:19264712

  18. Fertility preservation in women with endometriosis: for all, for some, for none?

    PubMed

    Somigliana, Edgardo; Viganò, Paola; Filippi, Francesca; Papaleo, Enrico; Benaglia, Laura; Candiani, Massimo; Vercellini, Paolo

    2015-06-01

    The increasing confidence with the techniques of oocyte and ovarian cortex freezing has prompted their potential use for patient categories other than those at risk of early menopause due to cancer treatments. Women affected by every iatrogenic or pathologic condition known to compromise ovarian function severely have been considered as potential candidates for fertility preservation. Among them, women with endometriosis may represent a particularly suitable group since they are at increased risk of premature ovarian exhaustion and about half of them will experience infertility. Based on the currently available notions on the intricate relationships between endometriosis, infertility and damage to the ovarian reserve, we speculate that fertility preservation may be of interest for women with endometriosis, in particular for those with bilateral unoperated endometriomas and for those who previously had excision of unilateral endometriomas and require surgery for a contralateral recurrence. Young age at diagnosis may be an independent but pivotal additional factor to be taken into consideration in the balance of the pros and cons of fertility preservation. On the other hand, we argue against the introduction of fertility preservation for endometriosis in routine clinical practice. To date, only few cases have been reported and there are insufficient data for robust cost-utility analyses. It is noteworthy that endometriosis is a relatively common disease and systematically including affected women in a fertility preservation program would have profound clinical, logistic and financial effects. More clinical data and in-depth economic analysis are imperative prior to recommending its routine use.

  19. The effect of hormones on endometriosis development.

    PubMed

    Parente Barbosa, C; Bentes De Souza, A M; Bianco, B; Christofolini, D M

    2011-08-01

    Endometriosis is a common gynecological condition in which tissue that is histologically similar to the endometrium with glands and/or stroma grows outside the uterine cavity and can lead to pelvic pain, dysmenorrhea and infertility. Many aspects of female reproductive function are strongly influenced by genetic factors and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as endometriosis. The importance of steroid hormones on endometriosis is unquestionable. The disease is most prevalent in women of reproductive age and regresses after menopause and its occurrence before menarche has not been reported. Sex steroids, estrogen and progesterone, are mainly produced in the ovaries and they regulate the growth of endometrial tissue, basically by stimulating and inhibiting cell proliferation, respectively. In addition, estrogen plays an important role in the regulation of cyclic gonadotropin release and in folliculogenesis. Numerous studies have been conducted to demonstrate the interaction of hormone and their receptors with endometriosis with conflict results. Besides, environmental chemicals, known as endocrine disruptors, have the capacity to mimic, block or modulate the endocrine system through the interaction with steroidal receptors. Recently evidences have proposed a putative role for ubiquitous environmental contaminants in the occurrence of endometriosis. Here, we reviewed significant articles regarding the interaction among endometriosis, hormones and genetic polymorphic variants.

  20. Effects of Previous Laparoscopic Surgical Diagnosis of Endometriosis on Pregnancy Outcomes

    PubMed Central

    Li, Hui; Zhu, Hong-Lan; Chang, Xiao-Hong; Li, Yi; Wang, Yue; Guan, Jing; Cui, Heng

    2017-01-01

    Background: The association between the previous history of endometriosis and obstetric outcomes is still ambiguous. This study aimed to evaluate the effects of previous history of operatively diagnosed endometriosis on pregnancy outcomes. Methods: A total of 98 primiparous women who had been diagnosed with endometriosis by previous laparoscopic surgery were included in this retrospective cohort study. Pregnancy outcomes were compared between these women (study group) who had a live birth and 300 women without endometriosis (control group) who had a live birth. In the study group, the pregnancy outcomes of 74 women who conceived naturally (no assisted reproductive technology [ART] subgroup) were simultaneously compared with 24 women who conceived by ART (ART subgroup). Results: Miscarriage was observed in 23 of 98 women with endometriosis (23.5%). There were 75 women who had a live birth after laparoscopic diagnosis of endometriosis in the study group eventually. On multivariate analysis, the postpartum hemorrhage rate increased significantly in the study group when compared with the control group (adjusted odds ratio: 2.265, 95% confidence interval: 1.062, 4.872; P = 0.034). There was an upward tendency of developing other pregnancy-related complications, such as preterm birth, placental abruption, placenta previa, cesarean section, fetal distress/anemia, and others in the study group than in the control group. However, the differences showed no statistical significance. Within the study group, the occurrence rate of postpartum hemorrhage and preterm birth was both higher in the ART subgroup than in the no ART subgroup. The differences both had statistical significance (44.4% vs. 17.5%, P = 0.024 and 27.8% vs. 1.8%, P = 0.010, respectively). At the same time, median (interquartile range) for gestational age at delivery in the ART subgroup was significantly shorter than that in the no ART subgroup (38 weeks [36–39 weeks] vs. 39 weeks [38–40 weeks]; P = 0

  1. A Case of Umbilical Endometriosis: Villar’s Nodule

    PubMed Central

    Dave, Atman A; Margolin, Daniel J

    2016-01-01

    Umbilical endometriosis is a fairly rare clinical entity with unclear pathogenesis. We report the case of a 27-year-old woman who presented with a painful umbilical mass and discharge. Imaging performed was inconclusive, and surgical excision of the site with margins revealed endometriosis on microscopic examination. The incidence of umbilical endometriosis, its pathogenesis, clinical manifestations, workup, and management are discussed. PMID:28097077

  2. Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro.

    PubMed

    Bruner-Tran, Kaylon L; Osteen, Kevin G; Taylor, Hugh S; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J

    2011-01-01

    Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

  3. Subcutaneous endometriosis: a rare cause of deep dyspareunia.

    PubMed

    Nigam, Aruna

    2014-01-06

    Endometriosis is a growth of endometrial tissue outside the uterine cavity which is responsive to hormonal stimulation. Extrapelvic endometriosis is less common of which skin is the most common site. The patient presents with mass, pain and cyclic symptoms. Subcutaneous endometriosis is very rare and has been reported only thrice in the literature. We report a case where the patient with lower abdominal pain and dyspareunia. Dyspareunia due to subcutaneous endometriosis has not been reported before when there is no evidence of intrapelvic endometriosis on laparoscopy.

  4. [Projective identification in human relations].

    PubMed

    Göka, Erol; Yüksel, Fatih Volkan; Göral, F Sevinç

    2006-01-01

    Melanie Klein, one of the pioneers of Object Relations Theory, first defined "projective identification", which is regarded as one of the most efficacious psychoanalytic concepts after the discovery of the "unconscious". Examination of the literature on "projective identification" shows that there are various perspectives and theories suggesting different uses of this concept. Some clinicians argue that projective identification is a primitive defense mechanism observed in severe psychopathologies like psychotic disorder and borderline personality disorder, where the intra-psychic structure has been damaged severely. Others suggest it to be an indispensable part of the transference and counter-transference between the therapist and the patient during psychotherapy and it can be used as a treatment material in the therapy by a skillful therapist. The latter group expands the use of the concept through normal daily relationships by stating that projective identification is one type of communication and part of the main human relation mechanism operating in all close relationships. Therefore, they suggest that projective identification has benign forms experienced in human relations as well as malign forms seen in psychopathologies. Thus, discussions about the definition of the concept appear complex. In order to clarify and overcome the complexity of the concept, Melanie Klein's and other most important subsequent approaches are discussed in this review article. Thereby, the article aims to explain its important function in understanding the psychopathologies, psychotherapeutic relationships and different areas of normal human relations.

  5. Radical Surgery for Endometriosis: Analysis of Quality of Life and Surgical Procedure

    PubMed Central

    De la Hera-Lazaro, Cristina M.; Muñoz-González, Jose L.; Perez, Reyes Oliver; Vellido-Cotelo, Rocío; Díez-Álvarez, Alvaro; Muñoz-Hernando, Leticia; Alvarez-Conejo, Carmen; Jiménez-López, Jesús S.

    2016-01-01

    OBJECTIVE The main aim of this study is to determine the improvement in quality of life in patients who have undergone radical surgery because of severe endometriosis. PATIENTS AND METHODS This nonrandomized interventional study (quasi experimental) was carried out between January 2009 and September 2014. A total of 46 patients with diagnosis of severe endometriosis were included. Radical surgery, including hysterectomy, was performed. Acting as their own control group, the patients were asked to fill in a validated questionnaire of quality of life [Endometriosis Health Profile-5 (EHP-5)] and a visual analog scale of pain at the moment of the preoperative visit (one month prior to surgery) and six months after the surgery. RESULTS Radical surgery for endometriosis was performed in 46 patients at our center over the period of six years. Among the patients, 73.9% of them had undergone previous surgery for endometriosis. In 82.6% of cases, a complete laparoscopic resection was carried out. Gastrointestinal tract resection was performed in 21.7%, and urinary tract resection was necessary in 8.7%. The mean age of the patients was 38.6 years. The rate of complications was 30.4%. Six months after the surgery, all items of the EHP-5 questionnaire had a lower score, which means an improvement in all aspects of quality of life related to endometriosis. The difference obtained between the scores before and after the surgery was statistically significant. The mean visual analog scale score before the surgery was 8.5, whereas it decreased to 1.4 after the surgery (P < 0.001). CONCLUSION Performing a radical surgery is a difficult decision to make; however, it can provide optimal results in terms of improvement of quality of life and, therefore, should be considered when conservative therapy fails. PMID:26966396

  6. Strong Association Between Endometriosis and Symptomatic Leiomyomas

    PubMed Central

    Nezhat, Camran; Li, Anjie; Abed, Sozdar; Balassiano, Erika; Soliemannjad, Rose; Nezhat, Ceana H.; Nezhat, Farr

    2016-01-01

    Background and Objectives: The relationship between leiomyoma and endometriosis is poorly understood. Both contribute to considerable pain and may cause subfertility or infertility in women. We conducted this retrospective study to assess the rate of coexistence of endometriosis in women with symptomatic leiomyoma. The primary outcome measured was the coexistence of histology-proven endometriosis in women with symptomatic leiomyoma. Methods: This is a retrospective review of a data-based collection of medical records of 244 patients treated at a tertiary medical center, who were evaluated for symptomatic leiomyoma from March 2011 through December 2015. Of those, 208 patients underwent laparoscopic or laparoscopic-assisted myomectomy or hysterectomy. All patients provided consent for possible concomitant diagnosis and treatment of endometriosis. The remaining 36 patients underwent medical therapy and were excluded from the study. All patients who had myomectomy or supracervical hysterectomy underwent minilaparotomy for extracorporeal morcellation and specimen removal beginning in April 2012. Results: Of the 208 patients with the presenting chief concern of symptomatic leiomyoma and who underwent surgical therapy, 181 had concomitant diagnoses of leiomyoma and endometriosis, whereas 27 had leiomyoma. Of the 27 patients, 9 also had adenomyosis. Patients with only fibroid tumors were, on average, 4.0 years older than those with endometriosis and fibroids (mean age, 44 vs 40 ± SD). Patients with both pathologies were also more likely to present with pelvic pain and nulliparity than those with fibroid tumors alone. Conclusions: In our patient population, 87.1% of patients with a chief concern of symptomatic fibroids also had a diagnosis of histology-proven endometriosis, which affirms the need for concomitant diagnosis and intraoperative treatment of both conditions. Overlooking the coexistence of endometriosis in women with symptomatic leiomyoma may lead to suboptimal

  7. Deep endometriosis: definition, pathogenesis, and clinical management.

    PubMed

    Vercellini, Paolo; Frontino, Giada; Pietropaolo, Giuliana; Gattei, Umberto; Daguati, Raffaella; Crosignani, Pier Giorgio

    2004-05-01

    "Deep endometriosis" includes rectovaginal lesions as well as infiltrative forms that involve vital structures such as bowel, ureters, and bladder. The available evidence suggests the same pathogenesis for deep infiltrating vesical and rectovaginal endometriosis (i.e., intraperitoneal seeding of regurgitated endometrial cells, which collect and implant in the most dependent portions of the peritoneal cavity and the anterior and posterior cul-de-sac, and trigger an inflammatory process leading to adhesion of contiguous organs with creation of false peritoneal bottoms). According to anatomic, surgical, and pathologic findings, deep endometriotic lesions seem to originate intraperitoneally rather than extraperitoneally. Also the lateral asymmetry in the occurrence of ureteral endometriosis is compatible with the menstrual reflux theory and with the anatomic differences of the left and right hemipelvis. Peritoneal, ovarian, and deep endometriosis may be diverse manifestations of a disease with a single origin (i.e., regurgitated endometrium). Based on different pathogenetic hypotheses, several schemes have been proposed to classify deep endometriosis, but further data are needed to demonstrate their validity and reliability. Drugs induce temporary quiescence of active deep lesions and may be useful in selected circumstances. Progestins should be considered as first-line medical treatment for temporary pain relief. However, in most cases of severely infiltrating disease, surgery is the final solution. Great importance must be given to complete and balanced counseling, as awareness of the real possibilities of different treatments will enhance the patient's collaboration.

  8. Association between endometriosis and hyperprolactinemia in infertile women

    PubMed Central

    Esmaeilzadeh, Seddigheh; Mirabi, Parvaneh; Basirat, Zahra; Zeinalzadeh, Mahtab; Khafri, Soraya

    2015-01-01

    Background: The association of endometriosis with hyperprolactinemia is controversial. Objective: The present study aimed to determine the frequency of endometriosis and association of prolactin with endometriosis in infertile women. Materials and Methods: 256 infertile women who underwent diagnostic laparoscopy for the evaluation of infertility, referred to Fatemezahra Infertility and Reproductive Health Research Center were included in a cross-sectional study. The presence of endometriosis was evaluated. To investigate the association of endometriosis with hyperprolactinemia, the patients whose infertility was not caused by endometriosis were included as control group. Serum prolactin (PRL) level was measured in both groups. The comparison of basal serum PRL levels between the two groups was performed, using independent t-test. One way ANOVA was used to determine PRL association with endometriosis stages. Results: The frequency of endometriosis was found to be 29%. PRL levels were significantly higher in endometriosis group compared to control group (23.02±1.25 vs. 17.22±1.22 respectively, p=0.004). Statistically significant associations were found between staging of endometriosis and prolactin levels (p=0.01). Conclusion: Hyperprolactinemia may be associated with endometriosis and its progression. PMID:26000006

  9. Models of endometriosis and their utility in studying progression to ovarian clear cell carcinoma.

    PubMed

    King, Claire M; Barbara, Cynthia; Prentice, Andrew; Brenton, James D; Charnock-Jones, D Stephen

    2016-01-01

    Endometriosis is a common benign gynaecological condition affecting at least 10% of women of childbearing age and is characterized by pain--frequently debilitating. Although the exact prevalence is unknown, the economic burden is substantial (∼$50 billion a year in the USA alone) and it is associated with considerable morbidity. The development of endometriosis is inextricably linked to the process of menstruation and thus the models that best recapitulate the human disease are in menstruating non-human primates. However, the use of these animals is ethically challenging and very expensive. A variety of models in laboratory animals have been developed and the most recent are based on generating menstrual-like endometrial tissue that can be transferred to a recipient animal. These models are genetically manipulable and facilitate precise mechanistic studies. In addition, these models can be used to study malignant transformation in epithelial ovarian carcinoma. Epidemiological and molecular evidence indicates that endometriosis is the most plausible precursor of both clear cell and endometrioid ovarian cancer (OCCA and OEA, respectively). While this progression is rare, understanding the underlying mechanisms of transformation may offer new strategies for prevention and therapy. Our ability to pursue this is highly dependent on improved animal models but the current transgenic models, which genetically modify the ovarian surface epithelium and oviduct, are poor models of ectopic endometrial tissue. In this review we describe the various models of endometriosis and discuss how they may be applicable to developing our mechanistic understanding of OCCA and OEA.

  10. Endometriosis

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  11. Endometriosis

    MedlinePlus

    ... abdominal - discharge Hysterectomy - laparoscopic - discharge Hysterectomy - vaginal - discharge Review Date 9/26/2015 Updated by: Daniel N. ... gynecology in private practice, West Palm Beach, FL. Review Provided by VeriMed Healthcare Network. Internal review and ...

  12. Small bowel endometriosis masquerading as regional enteritis.

    PubMed

    Minocha, A; Davis, M S; Wright, R A

    1994-05-01

    A 35-year-old female presented with recurrent right lower quadrant pain, nausea, and vomiting. She was afebrile with diffuse abdominal tenderness. Plain x-ray of abdomen revealed small bowel obstruction. A barium x-ray of the small bowel showed stricture of the terminal ileum. A CT scan of the abdomen showed a 6-cm mass in right lower quadrant. She was empirically managed as having Crohn's disease. She underwent laparotomy after failure of medical management with high-dose steroids. There was ulceration and narrowing of terminal ileum. Frozen sections revealed endometriosis. Ileocecectomy was performed. Histopathology of resected specimen confirmed the diagnosis of endometriosis, and there was no evidence of chronic inflammatory bowel disease or neoplasia. Ileal endometriosis should be considered in the differential diagnosis of Crohn's disease in menstruating females presenting with perimenstrual symptoms.

  13. Indomethacin and fertility in experimental endometriosis.

    PubMed

    Dargenio, R; Corbucci, M G; Lamanna, M A; Garcea, N

    1992-01-01

    Clinical and experimental evidence showed an increased concentration of prostaglandins in peritoneal fluid in cases of endometriosis. The aim of this study was to verify whether an antiprostaglandin drug can restore fertility in cases of endometriosis. For this reason endometriosis was induced in 4 groups of 10 rats. Group A was treated with indomethacin both in the pre-ovulatory and in the post-ovulatory phase. Group B was treated in the pre-ovulatory phase. Group C was treated in the post-ovulatory phase. Group D was not treated. Ten other rats (group E) underwent a sham operation and were used as a control. Twelve days after mating, gestational sacs and corpora lutea were counted and the nidation index was calculated. Only indomethacin administered during the pre-ovulatory phase completely restored fertility in these rats.

  14. Management of endometriosis in the infertile patient.

    PubMed

    Kistner, R W

    1975-12-01

    Infertility has a 30-40% incidence in women with endometriosis. However, conservative surgical procedures can result in pregnancy for 40-90% of these patients. The pregnancy rate is influenced by 5 factors: 1) extent of the disease, 2) age, 3) history of previous surgery for endometriosis, 4) duration of infertility before surgery, and 5) length of postsurgical follow-up. The factor responsible for infertility among women with endometriosis is believed to be an inadequacy of the tubo-ovarian motility secondary to fibrosis and scarring, which results in imperfect ovum acceptance by the fimbriae. Therapy encompasses 4 approaches: 1) prophylaxis, 2) observation and analgesia, 3) suppression of ovulation, and 4) surgical treatment. Pregnancy is suggested as the optimal prophylactic treatment for endometriosis since the symptoms and signs regress during gestation and for varying periods thereafter. This regression is probably due to a combination of anovulation and amenorrhea caused by adenohypophyseal suppression. It may also be due to a transformation of functioning endometriotic tissue into decidua by increasing levels of chorionic estrogen and progesterone. If pregnancy is not desired, anovulation can be secured by the administration of sex hormones. Pseudopregnancy for 6 months, induced by norgestrel plus ethinyl estradiol or norethynodrel plus mestranol, can lead to pregnancy in 50% of patients whose only abnormality is surface ovarian endometriosis within 1 year of cessation of therapy. Short periods of pseudopregnancy are also advocated after conservative surgery if all areas of endometriosis cannot be excised. 40-50% of these patients can expect to become pregnant within 24 months. The incidence of postoperative tubo-ovarian adhesions may be diminished by use of dexamethasone and promethazine.

  15. Long-Term Clinical Outcomes in Diabetic Rhesus Macaques (Macaca mulatta) Treated with Medroxyprogesterone Acetate for Endometriosis

    PubMed Central

    Connolly, Meghan A; Trentalange, Mark; Zeiss, Caroline J

    2016-01-01

    Depot medroxyprogesterone acetate (DMPA) is a common medical treatment for endometriosis in NHP. Because DMPA reportedly impairs glucoregulatory function in humans and rhesus macaques, as well as predisposes humans to diabetes mellitus (DM), we performed a retrospective study to further investigate its potential long-term clinical effects in animals with and without DM. Using a cohort of 29 rhesus macaques, we explored the hypotheses that DMPA treatment accelerates the onset of DM and that its use in rhesus macaques with endometriosis worsens clinical outcome measures (lifespan, body weight and body condition score). For both body weight and body condition score, a declining and statistically significant trend in mean values was evident as macaques developed either DM, or endometriosis or both. The addition of DMPA did not significantly alter this pattern. The presence of DM, endometriosis, or DMPA treatment statistically but not clinically significantly increased risk of death. Similarly, the presence of the 2 highly correlated variables endometriosis and DMPA treatment statistically but not clinically significantly increased the risk of incident DM. These results indicate that DMPA treatment was associated with worsening trends in lifespan and incident DM, however these trends did not achieve clinical significance in this cohort. PMID:27538865

  16. Vesicoovarian Fistula on an Endometriosis Abscessed Cyst

    PubMed Central

    Tran, C.; Even, M.; Carbonnel, M.; Preaux, F.; Isnard, F.; Rault, A.; Rouanne, M.; Ayoubi, J. M.

    2014-01-01

    We report the case of a patient who developed a vesicoovarian fistula on an endometriosis abscessed cyst. The patient presented with an advanced endometriosis stage IV complicated with a right ovarian abscessed cyst of 10 cm. A first coelioscopy with cystectomy was realized. After surgery, a voiding cystography highlighted a fistula between the ovarian abscess and the bladder. A second surgery by median laparotomy was realized with the resection of the right ovarian abscess and the resection of vesical fistula. PMID:25152819

  17. Endometriosis Is Associated with Rare Copy Number Variants

    PubMed Central

    Chettier, Rakesh; Ward, Kenneth; Albertsen, Hans M.

    2014-01-01

    Endometriosis is a complex gynecological condition that affects 6–10% of women in their reproductive years and is defined by the presence of endometrial glands and stroma outside the uterus. Twin, family, and genome-wide association (GWA) studies have confirmed a genetic role, yet only a small part of the genetic risk can be explained by SNP variation. Copy number variants (CNVs) account for a greater portion of human genetic variation than SNPs and include more recent mutations of large effect. CNVs, likely to be prominent in conditions with decreased reproductive fitness, have not previously been examined as a genetic contributor to endometriosis. Here we employ a high-density genotyping microarray in a genome-wide survey of CNVs in a case-control population that includes 2,126 surgically confirmed endometriosis cases and 17,974 population controls of European ancestry. We apply stringent quality filters to reduce the false positive rate common to many CNV-detection algorithms from 77.7% to 7.3% without noticeable reduction in the true positive rate. We detected no differences in the CNV landscape between cases and controls on the global level which showed an average of 1.92 CNVs per individual with an average size of 142.3 kb. On the local level we identify 22 CNV-regions at the nominal significance threshold (P<0.05), which is greater than the 8.15 CNV-regions expected based on permutation analysis (P<0.001). Three CNV's passed a genome-wide P-value threshold of 9.3×10−4; a deletion at SGCZ on 8p22 (P = 7.3×10−4, OR = 8.5, Cl = 2.3–31.7), a deletion in MALRD1 on 10p12.31 (P = 5.6×10−4, OR = 14.1, Cl = 2.7–90.9), and a deletion at 11q14.1 (P = 5.7×10−4, OR = 33.8, Cl = 3.3–1651). Two SNPs within the 22 CNVRs show significant genotypic association with endometriosis after adjusting for multiple testing; rs758316 in DPP6 on 7q36.2 (P = 0.0045) and rs4837864 in ASTN2 on 9q33.1 (P = 0.0002). Together

  18. Involvement of vascular endothelial growth factor −460 C/T, +405 G/C and +936 C/T polymorphisms in the development of endometriosis

    PubMed Central

    SZCZEPAŃSKA, MALGORZATA; MOSTOWSKA, ADRIANNA; WIRSTLEIN, PRZEMYSLAW; SKRZYPCZAK, JANA; JAGODZIŁSKI, PAWEŁ P.

    2015-01-01

    There are inconsistent data on the contribution of vascular endothelial growth factor (VEGF) −460 C/T (rs833061), +405 G/C (rs2010963) and +936 C/T (rs3025039) single-nucleotide polymorphisms (SNPs) to endometriosis in different ethnicities. Therefore, using high-resolution melting curve analysis, the present study examined the distribution of these SNPs in females with endometriosis-related infertility and a control group. None of the three VEGF SNPs were associated with endometriosis-related infertility in the dominant and recessive models. The lowest P-values of the trend were observed for the VEGF +936 C/T (rs3025039) SNP in endometriosis-related infertility (Ptrend =0.149). Similarly, haplotype analyses of VEGF SNPs did not demonstrate any SNP combination as a risk for endometriosis-related infertility, and the lowest overall P-values, P=0.141 and Pcorr =0.395, were observed for a haplotype (TGT) of the above SNPs. Taken together, these results did not demonstrate the contribution of VEGF C/T, +405 G/C and +936 C/T SNPs to endometriosis-related infertility. PMID:26075076

  19. Bladder Endometriosis Mimicking TCC - A Case Report.

    PubMed

    Gupta, Asish; Bhatnagar, Atul; Seth, B N; Dang, Arbinder; Gupta, Vineeta

    2016-02-01

    Endometriosis is the ectopic presence of endometrial tissue outside the uterus. Though on its own endometriosis is not a rare lesion, the involvement of the urinary tract is rare but with the bladder being the most commonly affected organ. Endometriosis is usually seen in females between the ages of 30-40 years and may occur due to fluctuating levels of oestrogen and progesterone. Clinically the patient maybe asymptomatic or show symptoms of dysmenorrhea, irregular or heavy periods, pain in the pelvic area, lower abdomen or in the back. It has been suggested that ultrasonography should be done either before or during menstruation as the lesion becomes more evident and a biopsy taken during this period is a strong aid in reaching a final diagnosis. We report here an unusual case of bladder endometriosis where the patient came with severe pelvic pain and an endoluminal mass seen on the ultrasonographic report. Based on these findings a differential of transitional cell carcinoma was given which was ruled out based on the cystoscopic findings.

  20. DIOXINS AND ENDOMETRIOSIS: A PLAUSIBLE HYPOTHESIS

    EPA Science Inventory

    A potential connection exists between the increasing prevalence of endometriosis and exposure to organochlorine chemicals. There is evidence that dioxin (2,3,7,8-TCDD) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of end...

  1. 17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis.

    PubMed

    Bulun, Serdar E; Cheng, You-Hong; Pavone, Mary Ellen; Yin, Ping; Imir, Gonca; Utsunomiya, Hiroki; Thung, Stephen; Xue, Qing; Marsh, Erica E; Tokunaga, Hideki; Ishikawa, Hiroshi; Kurita, Takeshi; Su, Emily J

    2010-01-01

    Estradiol (E2) stimulates the growth and inflammation in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Several clinical and laboratory-based observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptor (PR). In normal endometrium, progesterone acts via PR on stromal cells to induce secretion of paracrine factor(s) that in turn stimulate neighboring epithelial cells to express the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (HSD17B2). HSD17B2 is an extremely efficient enzyme and rapidly metabolizes the biologically potent estrogen E2 to weakly estrogenic estrone. In endometriotic tissue, progesterone is incapable of inducing epithelial HSD17B2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate HSD17B2 may be due to the very low levels of PR observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this mitogen. The molecular details of this physiological paracrine interaction between the stroma and epithelium in normal endometrium and its lack thereof in endometriosis are discussed.

  2. Rectal mucosal endometriosis primarily misinterpreted as adenocarcinoma: a case report and review of literature

    PubMed Central

    Chen, Hui; Luo, Qiuping; Liu, Shaoyan; Xiong, Hanzhen; Jiang, Qingping

    2015-01-01

    Endometriosis involving intestinal mucosa is relatively uncommon. It poses a diagnostic challenge for clinicians and pathologists. We herein report a case of colonoscopic specimen revealing rectal mucosal endometriosis. A 39-year-old woman complained of red rectal bleeding and intermittent abdominal pain. Colonoscopic examination showed a rectal mass with ulceration and circum wall involvement. Biopsy was processed in the suspicious of carcinoma. Morphologically, irregular glands replaced residual colorectal ones, displayed mucin depletion, nuclear stratification and subtile subnuclear vacuoles. The stroma was full of spindle cells with abundant pink cytoplasm and unclear boundary. Due to subjectively interpreting as dysplastic glands in desmoplastic setting, primary rectal adenocarcinoma was firstly raised. Immunohistochemically, CK7, ER and CD10 identified the essence of ectopic endometrium. CK20 and CDX2 highlighted residual glands. In case of misdiagnosis, any pathologists should be aware of intestinal endometriosis for each female’s colorectal biopsy, especially for that morphology not typical for primary adenocarcinoma or endometriosis. Reading slides carefully combined with a panel of immunomarkers would solve the pitfall. PMID:26191316

  3. Surgically treated ovarian endometriosis association with BRCA1 and BRCA2 mutations.

    PubMed

    Aviel-Ronen, Sarit; Soriano, David; Shmuel, Elyasaf; Schonman, Ron; Rosenblatt, Kinneret; Zadok, Oranit; Vituri, Aya; Seidman, Daniel; Barshack, Iris; Cohen, Yoram

    2014-04-01

    Endometriosis is associated with an increased risk of ovarian cancer. Few studies have also shown increased risk of breast cancer. BRCA1/2 mutations are linked to an increased risk of breast and ovarian cancers but their relation to endometriosis is unknown. The objective of this study was to examine the mutation rate of BRCA1/2 among women with surgically treated ovarian endometriosis. We collected 126 specimens from Jewish Ashkenazi women with endometriotic (76) and control non-endometriotic (50) ovarian cysts, reviewed the pathological diagnoses and extracted DNA from all samples. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), samples were examined for the founder germline mutations of BRCA1/2, most common among Ashkenazi Jews. The rate of mutations in each group was calculated and compared. BRCA1/2 mutation rate was 1/76 (1.3%) in the endometriotic cyst study group and 1/50 (2%) in the control non-endometriotic cysts, showing no statistically significant difference between the groups (p=0.84). BRCA1/2 mutation rate was similar to the previously reported rate among Jewish Ashkenazi women. BRCA1/2 mutation rates in patients with endometriotic ovarian cysts and with non-endometriotic ovarian cysts are similar. A larger cohort is required to completely exclude the possibility of an association between BRCA1/2 mutations and surgically treated endometriosis.

  4. Aberrant gene expression profile in a mouse model of endometriosis mirrors that observed in women

    PubMed Central

    Pelch, Katherine E.; Schroder, Amy L.; Kimball, Paul A.; Sharpe-Timms, Kathy L.; Davis, J. W.; Nagel, Susan C.

    2010-01-01

    Objective To define the altered gene expression profile of endometriotic lesions in a mouse model of surgically-induced endometriosis Design Autologous experimental mouse model. Setting Medical school department. Animals Adult C57Bl6 mice. Intervention(s) Endometriosis was surgically-induced by auto-transplantation of uterine tissue to the intestinal mesentery. Endometriotic lesions and eutopic uteri were recovered at 3 or 29 days post-induction. Main Outcome Measure(s) Altered gene expression was measured in the endometriotic lesion relative to the eutopic uterus by genome wide cDNA microarray analysis and was confirmed by real time RT-PCR for six genes. Relevant categories of altered genes were identified using gene ontology analysis to determine groups of genes enriched for altered expression. Result(s) The expression of 479 and 114 genes was altered in the endometriotic lesion compared to the eutopic uterus at 3 or 29 days post-induction, respectively. Gene ontology enrichment analysis revealed that genes associated with the extracellular matrix, cell adhesions, immune function, cell growth, and angiogenesis were altered in the endometriotic lesion compared to the eutopic uterus. Conclusion(s) Based on gene expression analysis, the mouse model of surgically-induced endometriosis appears to be a good model for studying the pathophysiology and treatment of endometriosis. PMID:19473656

  5. Estrogen-induced CCN1 is critical for establishment of endometriosis-like lesions in mice.

    PubMed

    Zhao, Yuechao; Li, Quanxi; Katzenellenbogen, Benita S; Lau, Lester F; Taylor, Robert N; Bagchi, Indrani C; Bagchi, Milan K

    2014-12-01

    Endometriosis is a prevalent gynecological disorder in which endometrial tissue proliferates in extrauterine sites, such as the peritoneal cavity, eventually giving rise to painful, invasive lesions. Dysregulated estradiol (E) signaling has been implicated in this condition. However, the molecular mechanisms that operate downstream of E in the ectopic endometrial tissue are unknown. To investigate these mechanisms, we used a mouse model of endometriosis. Endometrial tissue from donor mice was surgically transplanted on the peritoneal surface of immunocompetent syngeneic recipient mice, leading to the establishment of cystic endometriosis-like lesions. Our studies revealed that treatment with E led to an approximately 3-fold increase in the lesion size within a week of transplantation. E also caused a concomitant stimulation in the expression of connective tissue growth factor/Cyr61/Nov (CCN1), a secreted cysteine-rich matricellular protein, in the lesions. Interestingly, CCN1 is highly expressed in human ectopic endometriotic lesions. To address its role in endometriosis, endometrial tissue from Ccn1-null donor mice was transplanted in wild-type recipient mice. The resulting ectopic lesions were reduced up to 75% in size compared with wild-type lesions due to diminished cell proliferation and cyst formation. Notably, loss of CCN1 also disrupted the development of vascular networks in the ectopic lesions and reduced the expression of several angiogenic factors, such as vascular endothelial growth factor-A and vascular endothelial growth factor-C. These results suggest that CCN1, acting downstream of E, critically controls cell proliferation and neovascularization, which support the growth and survival of endometriotic tissue at ectopic sites. Blockade of CCN1 signaling during the early stages of lesion establishment may provide a therapeutic avenue to control endometriosis.

  6. Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo.

    PubMed

    Khoufache, Khaled; Bazin, Sylvie; Girard, Karine; Guillemette, Julie; Roy, Marie-Christine; Verreault, Jean-Pierre; Al-Abed, Yousef; Foster, Warren; Akoum, Ali

    2012-01-01

    Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential

  7. Macrophage Migration Inhibitory Factor Antagonist Blocks the Development of Endometriosis In Vivo

    PubMed Central

    Khoufache, Khaled; Bazin, Sylvie; Girard, Karine; Guillemette, Julie; Roy, Marie-Christine; Verreault, Jean-Pierre; Al-Abed, Yousef; Foster, Warren; Akoum, Ali

    2012-01-01

    Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential

  8. Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

    PubMed Central

    Greaves, Erin; Temp, Julia; Esnal-Zufiurre, Arantza; Mechsner, Sylvia; Horne, Andrew W.; Saunders, Philippa T.K.

    2016-01-01

    Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1–differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. PMID:26073038

  9. Catamenial hemoptysis accompanied by subcutaneous endometriosis treated with combination therapy

    PubMed Central

    Jang, Hye-In; Kim, Sung-Eun; Lee, Yoo-Young; Choi, Chel-Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

    2017-01-01

    Extra pelvic endometriosis is considered to be rare. This paper reports a case of catamenial hemoptysis accompanied by subcutaneous endometriosis in 26-year-old woman. A computed tomography scan of the chest revealed a focal ground-glass opacity lesion in the posterior segment of the right upper lobe. Histopathology confirmed the diagnosis of endometriosis of right lung and concurrent subcutaneous endometriosis. She was treated with surgical resection of the endometriosis lesions on two different sites and perioperative gonadotropin-releasing hormone agonist therapy. The 6-month follow-up after combination treatment showed no recurrence. Though long-term follow-up result is needed, aggressive treatment using combination treatment (surgery and perioperative medication) should be considered for symptomatic extra pelvic endometriosis. PMID:28344969

  10. Introduction: new tools for enhancing collaborative endometriosis research.

    PubMed

    Casper, Robert F

    2014-11-01

    This issue of Fertility and Sterility contains four articles by the World Endometriosis Research Foundation whose present objective is global standardization of the collection of phenotypic data and biological samples, designated as the Endometriosis Phenome and Biobanking Harmonisation Project. The aim is to facilitate large-scale international, multicenter trials that are robust, and will result in biomarker and treatment targets to advance research in endometriosis.

  11. Down-regulation of the CYP19A1 gene in cumulus cells of infertile women with endometriosis.

    PubMed

    Barcelos, Ionara Diniz E S; Donabella, Flávia Capello; Ribas, Cristiana Padovan; Meola, Juliana; Ferriani, Rui Alberto; de Paz, Cláudia Cristina Paro; Navarro, Paula A

    2015-05-01

    Aromatase plays a fundamental role in the establishment of oocyte quality, which might be compromised in infertile women with endometriosis. The expression of the CYP19A1 gene (that encodes aromatase) was compared in cumulus cells and oestradiol concentrations in the follicular fluid of infertile women with and without endometriosis submitted to ovarian stimulation for intracytoplasmic sperm injection. Cumulus cells were isolated and the expression of the CYP19A1 was quantitated through real-time polymerase chain reaction. Oestradiol concentrations in follicular fluid were measured by chemiluminescence immunoassay. A lower expression of the CYP19A1 in the cumulus cells of infertile women with endometriosis was observed compared with controls (0.17 ± 0.13 and 0.56 ± 0.12, respectively), and no significant difference in the follicular fluid oestradiol concentrations was observed between groups. Our results show reduced expression of the CYP19A1 in cumulus cells of infertile women with endometriosis, which may play a role in the pathogenesis of endometriosis-related infertility.

  12. Differential gene expression by 1,25(OH)2D3 in an endometriosis stromal cell line.

    PubMed

    Ingles, Sue Ann; Wu, Liang; Liu, Benjamin T; Chen, Yibu; Wang, Chun-Yeh; Templeman, Claire; Brueggmann, Doerthe

    2017-01-28

    Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH)2D3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH)2D3, and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH)2D3. Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH)2D3 treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments.

  13. High rate of allergies among women with endometriosis.

    PubMed

    Matalliotakis, I; Cakmak, H; Matalliotakis, M; Kappou, D; Arici, A

    2012-04-01

    Women with endometriosis frequently suffer from autoimmune inflammatory diseases, allergies and asthma. This study was conducted to examine whether the prevalence of allergies is higher in patients with endometriosis than in the control group, and to show potential correlation with endometriosis stages. We evaluated the medical files of 501 women with laparoscopically-diagnosed endometriosis and 188 women without endometriosis enrolled in Yale University Hospital. Main outcome measures used were allergy on medications, complaints of sinus or perennial allergic rhinitis, asthma, family history of allergic disease, and correlation with stages of endometriosis. Our results indicated that the overall risk of women with endometriosis and positive history of allergies was 4.28 (95% CI, 2.9-6.3) (p < 0.001). Significant excesses were identified for medications, sinus allergic rhinitis, and asthma; also, women with endometriosis were significantly more likely to report a positive family history of allergies. Overall, our study indicated a link between endometriosis and increased risk of allergic autoimmune disorders that should further be explored.

  14. Inguinal endometriosis or irreducible hernia? A difficult preoperative diagnosis.

    PubMed

    Miranda, L; Settembre, A; Capasso, P; Piccolboni, D; De Rosa, N; Corcione, F

    2001-03-01

    Two cases of endometriosis infiltrating the round ligament and associated with an inguinal hernia are presented. The initial diagnosis was irreducible hernia, since this rare association often causes unusual preoperative symptoms and diagnostic problems. Diagnosis is frequently made by histologic examination. Surgery is the treatment of choice both for hernia and for endometriosis, and is locally curative. However, in a fertile woman with a painful mass in the inguinal region the possibility of endometriosis should be considered, and if suspected at inguinal exploration a laparoscopy should be made to rule out the presence of intraperitoneal endometriosis.

  15. Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Liu, Shuangge; Xin, Xiaoyan; Hua, Teng; Shi, Rui; Chi, Shuqi; Jin, Zhishan; Wang, Hongbo

    2016-01-01

    Background/Objective Vascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis. Methods A systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis. The databases were: PubMed, Web of Science, BIOSIS, Embase, and CNKI. The quality of included studies was assessed using the SYRCLE tool. The random-effect models were used to combine the results of selected studies. Heterogeneity was assessed using H2statistic and I2 statistic. Subgroup analyses were performed to determine the source of heterogeneity in endometriosis scores and follicle numbers. Results We identified 13 studies that used anti-VEGF/VEGFR agents in various animal models. The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) –0.96, 95% CI –1.31 to –0.62; P < 0.0001) and weight (SMD –1.70, 95% CI –2.75 to –0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis (risk ratio 0.26, 95% CI 0.07 to 0.93; P = 0.038) and endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001); the number of follicles were similar (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08). Conclusions Anti-VEGF/VEGFR agents appeared to inhibit the growth of endometriosis, with no effect on ovarian function. Anti-angiogenic therapy may be a novel strategy in treating endometriosis. PMID:27855197

  16. Cyst fluid hemoglobin species in endometriosis and its malignant transformation: The role of metallobiology

    PubMed Central

    IWABUCHI, TAKUYA; YOSHIMOTO, CHIHARU; SHIGETOMI, HIROSHI; KOBAYASHI, HIROSHI

    2016-01-01

    The aim of the present study was to assess the relative concentrations of hemoglobin (Hb) species in endometriosis as a possible indicator of malignancy. Electronic absorption spectroscopy was employed to quantify the Hb species present in the cyst fluid collected from 8 patients with endometriosis-associated ovarian cancer (EAOC), and compared with those present in the cyst fluid of 35 patients with benign endometriotic cysts. The 620/580 nm ratio in the electronic absorption spectrum, which was used as a surrogate indicator of the methemoglobin (metHb)/(oxyhemoglobin+metHb) ratio, was measured in each cyst fluid by ultraviolet/visible grating spectrophotometric microplate reader. The optimal cutoff value was defined according to the analysis of receiver operating characteristic (ROC) curve. The sensitivity and specificity of detection were calculated on the basis of the cutoff value to differentiate EAOC from endometriosis. The 620/580 nm ratio of cyst fluid in EAOC patients was much lower than that measured in women with benign cysts (0.389±0.266 vs. 0.666±0.188, P=0.021). ROC curve analysis performed using 0.35 as the optimal cutoff value indicated that the 620/580 nm ratio had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value of 62.5, 100.0, 100.0 and 92.1%, respectively, in the diagnosis of EAOC. In conclusion, metHb is one of the most abundant Hb species in benign cysts, and the absorption 620/580 nm ratio of cyst fluid exhibits high specificity and PPV as a surveillance test for the early detection of malignant transformation of endometriosis. Thus, metallobiology highlights diverse features involved in Hb homeostasis and the pathogenesis of malignant transformation of endometriosis. PMID:27123121

  17. A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR).

    PubMed

    Leyendecker, Gerhard; Wildt, Ludwig

    2011-03-01

    Pelvic endometriosis, deeply infiltrating endometriosis and uterine adenomyosis share a common pathophysiology and may be integrated into the physiological mechanism and new nosological concept of 'tissue injury and repair' (TIAR) and may, in this context, just represent the extreme of a basically physiological, estrogen-related mechanism that is pathologically exaggerated in an extremely estrogen-sensitive reproductive organ. The acronym TIAR describes a fundamental and apparently ubiquitous biological system that becomes operative in mesenchymal tissues following tissue injury and, upon activation, results in the local production of estradiol. Endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatisations, with activation of the TIAR mechanism. With ongoing traumatisations, such sites of inflammation might accumulate and the increasingly produced estrogens interfere in a paracrine fashion with ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt autotraumatisation of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis a causal event early in the reproductive period of life must be postulated, rapidly leading to archimetral hyperestrogenism and uterine hyperperistalsis. In late premenopausal adenomyosis such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life accumulates to the same extent of microtraumatisation. With activation of the TIAR mechanism followed by

  18. Increased risk of placenta previa is associated with endometriosis and tubal factor infertility in assisted reproductive technology pregnancy.

    PubMed

    Takemura, Yuri; Osuga, Yutaka; Fujimoto, Akihisa; Oi, Nagisa; Tsutsumi, Ryo; Koizumi, Minako; Yano, Tetsu; Taketani, Yuji

    2013-02-01

    Although assisted reproductive technology (ART) is suspected to increase the risk of placenta previa, a life-threatening complication of pregnancy, the reason is poorly understood. We recruited consecutive 318 pregnancies conceived by ART in our clinic and examined relation of ten variables, i.e. maternal age, gravidity, parity, male or female fetus, previous abortion, previous cesarean delivery, endometriosis, ovulatory disorder, tubal disease, and male infertility, to placenta previa, by logistic regression analysis. As a result, we found that endometriosis (odds ratio = 15.1; 95% CI = 7.6-500.0) and tubal disease (odds ratio = 4.4; 95% CI = 1.1-26.3) were significantly associated with placenta previa. It would be preferable to take the increased risk of placenta previa into account in treating ART pregnancy with endometriosis and tubal disease.

  19. Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain.

    PubMed

    Neziri, Alban Y; Bersinger, Nick A; Andersen, Ole K; Arendt-Nielsen, Lars; Mueller, Michael D; Curatolo, Michele

    2014-01-01

    Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

  20. Intrauterine endometriotic cyst at the site of previous cesarean scar; scar endometriosis.

    PubMed

    Isci, H; Gonenc, G; Yigiter, A B; Guducu, N; Dünder, I

    2015-01-01

    Uterine scar endometriosis is an extremely rare entitiy. As the surgical procedures of the uterus increases through time, scar endometriosis may be diagnosed more often in the future. A case of uterine scar endometriosis is presented with complaints of menstruation lasting one day with associated pelvic pain. When a cystic mass in the site of previous surgery is diagnosed, scar endometriosis must be considered.

  1. Endometriosis: a high-risk population for major chronic diseases?

    PubMed Central

    Kvaskoff, Marina; Mu, Fan; Terry, Kathryn L.; Harris, Holly R.; Poole, Elizabeth M.; Farland, Leslie; Missmer, Stacey A.

    2015-01-01

    BACKGROUND Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. METHODS We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. RESULTS We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If

  2. Metal status in human endometrium: Relation to cigarette smoking and histological lesions

    SciTech Connect

    Rzymski, Piotr; Rzymski, Paweł; Tomczyk, Katarzyna; Niedzielski, Przemysław; Jakubowski, Karol; Poniedziałek, Barbara; Opala, Tomasz

    2014-07-15

    Human endometrium is a thick, blood vessel-rich, glandular tissue which undergoes cyclic changes and is potentially sensitive to the various endogenous and exogenous compounds supplied via the hematogenous route. As recently indicated, several metals including Cd, Pb, Cr and Ni represent an emerging class of potential metalloestrogens and can be implicated in alterations of the female reproductive system including endometriosis and cancer. In the present study, we investigated the content of five metals: Cd, Cr, Ni, Pb and Zn in 25 samples of human endometrium collected from Polish females undergoing diagnostic or therapeutic curettage of the uterine cavity. The overall mean metal concentration (analyzed using microwave induced plasma atomic emission spectrometry MIP-OES) decreased in the following order: Cr>Pb>Zn>Ni>Cd. For the first time it was demonstrated that cigarette smoking significantly increases the endometrial content of Cd and Pb. Concentration of these metals was also positively correlated with years of smoking and the number of smoked cigarettes. Tissue samples with recognized histologic lesions (simple hyperplasia, polyposis and atrophy) were characterized by a 2-fold higher Cd level. No relation between the age of the women and metal content was found. Our study shows that human endometrium can be a potential target of metal accumulation within the human body. Quantitative analyses of endometrial metal content could serve as an additional indicator of potential impairments of the menstrual cycle and fertility. - Highlights: • Cd, Cr, Ni, Pb and Zn are detectable in human endometrium. • Mean metal content in human endometrium decreases in Cr>Pb>Zn>Ni>Cd order. • Cigarettes smoking increases endometrial content of Cd and Pb. • Lesioned endometrial tissue was characterized by higher metal contents.

  3. [Essential data set's archetypes for nursing care of endometriosis patients].

    PubMed

    Spigolon, Dandara Novakowski; Moro, Claudia Maria Cabral

    2012-12-01

    This study aimed to develop an Essential Data Set for Nursing Care of Patients with Endometriosis (CDEEPE), represented by archetypes. An exploratory applied research with specialists' participation that was carried out at Heath Informatics Laboratory of PUCPR, between February and November of 2010. It was divided in two stages: CDEEPE construction and evaluation including Nursing Process phases and Basic Human Needs, and archetypes development based on this data set. CDEEPE was evaluated by doctors and nurses with 95.9% of consensus and containing 51 data items. The archetype "Perception of Organs and Senses" was created to represents this data set. This study allowed identifying important information for nursing practices contributing to computerization and application of nursing process during care. The CDEEPE was the basis for archetype creation, that will make possible structured, organized, efficient, interoperable, and semantics records.

  4. TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis.

    PubMed

    Au, Heng-Kien; Chang, Jui-Hung; Wu, Yu-Chih; Kuo, Yung-Che; Chen, Yu-Hsi; Lee, Wei-Chin; Chang, Te-Sheng; Lan, Pei-Chi; Kuo, Hung-Chih; Lee, Kha-Liang; Lee, Mei-Tsu; Tzeng, Chii-Ruey; Huang, Yen-Hua

    2015-01-01

    Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell

  5. TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis

    PubMed Central

    Au, Heng-Kien; Chang, Jui-Hung; Wu, Yu-Chih; Kuo, Yung-Che; Chen, Yu-Hsi; Lee, Wei-Chin; Chang, Te-Sheng; Lan, Pei-Chi; Kuo, Hung-Chih; Lee, Kha-Liang; Lee, Mei-Tsu; Tzeng, Chii-Ruey; Huang, Yen-Hua

    2015-01-01

    Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell

  6. Laparoscopic surgery for intestinal and urinary endometriosis.

    PubMed

    Redwine, D B; Sharpe, D R

    1995-12-01

    Intestinal and urinary tract involvement by endometriosis may be symptomatic, particularly when invasive disease is present. Even in expert hands, complete excision of all invasive disease cannot be accomplished laparoscopically in every case. The practitioner must balance enthusiasm for the advantages of a laparoscopic approach with limitations of time and skill. Laparoscopy should be abandoned in a particular case if a better job can be performed by laparotomy. Hysterectomy with castration may not relieve symptoms due to invasive disease.

  7. Colonic Endometriosis: Dig Deeper for Diagnosis

    PubMed Central

    Badipatla, Kanthi Rekha; Vupputuri, Anisha; Niazi, Masooma; Blaise, Marie-Nirva; Nayudu, Suresh Kumar

    2017-01-01

    Endometriosis is a common gynecological condition wherein there is an ectopic implantation of the uterine endometrial tissue. While several diagnostic modalities are described for the condition, laparoscopy remains the gold standard. There is still an undiscovered area to diagnose colonic endometriosis at an earlier stage. We present a case report of a reproductive age woman with cyclical rectal bleeding diagnosed with colonic endometriosis with colonoscopy and biopsy using saline injection lift and sampling technique. We in our report try to impress the fact that this differential should always be considered in the appropriate clinical setting, especially in women of childbearing age and in such cases, deeper tissue sampling techniques should be sought for, given better diagnostic yield. This may be clinically important given that it may aid in earlier diagnosis and thereby early initiation of appropriate therapy before the disease takes a complicated route. It may also be helpful in avoiding unnecessary surgery, along with the morbidity, complications and costs associated with same. PMID:28270880

  8. The dilemma of endometriosis: is consensus possible with an enigma?

    PubMed

    Nezhat, Camran; Littman, Eva D; Lathi, Ruth B; Berker, Bulent; Westphal, Lynn M; Giudice, Linda C; Milki, Amin A

    2005-12-01

    Many will agree that the use of laparoscopy to diagnose and potientially treat endometriosis in patients who suffer from infertility has been superseded by IVF and sometimes oocyte donation, especially in older patients. The findings of our study add another dimension to management of endometriosis in the setting of infertility and emphasize the importance of keeping laparoscopy in the infertility management equation.

  9. A case of bifocal endometriosis involving a pfannenstiel incision.

    PubMed

    Evsen, Mehmet Sidik; Sak, Muhammet Erdal; Yalinkaya, Ahmet; Firat, Ugur; Caca, Fatma Nur

    2011-01-01

    A 25-year-old woman was referred to our clinic for atypical cyclic pain and masses at both ends of a Pfannenstiel incision scar. Ultrasound of the anterior abdominal wall showed two masses. Both masses were hypoechoic, heterogeneous lesions located at opposite ends of the scar. The lesions were surgically excised with. Microscopic examination revealed endometrial gland structures with endometrial stroma in fibroadipose tissue in sections of both specimens indicative of endometriosis. Incisional endometriosis (IE) is a form of extrapelvic endometriosis especially in scars of obstetric or gynecologic surgery IE may be multifocal at surgical scars. We report the a case of bifocal incisional endometriosis in Pfannesteil scar. Whole scar evaluation should be done for incisional endometriosis and surgical excision should be performed for treatment.

  10. Implications of immune dysfunction on endometriosis associated infertility.

    PubMed

    Miller, Jessica E; Ahn, Soo Hyun; Monsanto, Stephany P; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

    2017-01-24

    Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.

  11. Implications of immune dysfunction on endometriosis associated infertility

    PubMed Central

    Miller, Jessica E.; Ahn, Soo Hyun; Monsanto, Stephany P.; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

    2017-01-01

    Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure. PMID:27740937

  12. The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis.

    PubMed

    Delgado-Rosas, Francisco; Gómez, Raúl; Ferrero, Hortensia; Gaytan, Francisco; Garcia-Velasco, Juan; Simón, Carlos; Pellicer, Antonio

    2011-11-01

    Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50  μg/kg per day oral Cb2, or 50 or 200  μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.

  13. Seeking New Treatments for Endometriosis

    MedlinePlus

    ... Researchers in the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR) have used genomic information ... cell population in the non-human primate. Human Reproduction, 27 (6), 1712–1722. PMID: 22442246 Buck Louis, ...

  14. The Computerized Human Relations Program - Humrelat -

    ERIC Educational Resources Information Center

    Cassel, Russell N.; And Others

    1973-01-01

    This is the report of a study accomplished in two separate parts: (1) Part I dealt with evaluation of an existing course of instruction in human relations at The Moraine Park Technical Institute, and (2) Part II dealt with the development of a proposed course of instruction in human relations for the technical institute. (Author)

  15. Appendix O. The Human Relations School.

    ERIC Educational Resources Information Center

    Fox Robert S.; Lippitt, Ronald

    This document presents a model for a Human Relations School, an educational system in which attention is formally focused on the human relations aspects of the school, those aspects traditionally subordinated to cognitive objectives. Ten basic assumptions are listed which led to the identification of a set of goal areas. Five to 10…

  16. The Principal and Human Relations.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Human Relations.

    This booklet offers general guidelines and recommendations on how to develop and exercise the interpersonal skills required of a successful school principal. Attention is devoted to the basic principles of effective communication and personal interaction, with emphasis on the principal's relations with students, teachers, and members of the…

  17. The sensitivity of the DNA damage checkpoint prevents oocyte maturation in endometriosis

    PubMed Central

    Hamdan, Mukhri; Jones, Keith T.; Cheong, Ying; Lane, Simon I. R.

    2016-01-01

    Mouse oocytes respond to DNA damage by arresting in meiosis I through activity of the Spindle Assembly Checkpoint (SAC) and DNA Damage Response (DDR) pathways. It is currently not known if DNA damage is the primary trigger for arrest, or if the pathway is sensitive to levels of DNA damage experienced physiologically. Here, using follicular fluid from patients with the disease endometriosis, which affects 10% of women and is associated with reduced fertility, we find raised levels of Reactive Oxygen Species (ROS), which generate DNA damage and turn on the DDR-SAC pathway. Only follicular fluid from patients with endometriosis, and not controls, produced ROS and damaged DNA in the oocyte. This activated ATM kinase, leading to SAC mediated metaphase I arrest. Completion of meiosis I could be restored by ROS scavengers, showing this is the primary trigger for arrest and offering a novel clinical therapeutic treatment. This study establishes a clinical relevance to the DDR induced SAC in oocytes. It helps explain how oocytes respond to a highly prevalent human disease and the reduced fertility associated with endometriosis. PMID:27841311

  18. Extraperitoneal Endometriosis With Catamenial Pneumothoraces: A Review of the Literature

    PubMed Central

    Roberts, Lisa M.; Reich, Harry

    2003-01-01

    Objective: To present a case of recurrent catamenial pneumothorax and diaphragmatic endometriosis that was managed thoracoscopically. A review of the literature is also presented. Methods: A-28-year-old woman presented with bloody stools, chronic constipation, and chest pain. A review of systems was positive for monthly chest pain associated with her menses. A preoperative chest x-ray revealed a right pneumothorax. Colonoscopy revealed biopsy proven endometriosis of the sigmoid colon. A pelvic computed tomography scan revealed bilateral complex, cystic and solid adenexal lesions. Results: A right thoracoscopy was performed. A lesion on the right hemidiaphragm was excised and confirmed to be endometriosis. A wedge section of lung tissue containing a bleb was resected and also contained endometriosis. Three months later, the patient underwent laparoscopic excision of her pelvic endometriosis, including a low anterior rectal resection. Five months later, she presented again with right-sided chest pain. A thoracoscopic right total pleurectomy was performed for recurrent pneumothorax. Conclusion: Pulmonary endometriosis may present as chest pain, shortness of breath, or hemoptysis associated with menstrual cycles. This case emphasizes the importance of a careful review of systems in patients with known endometriosis. Management now includes an endoscopic alternative and all of its known benefits. PMID:14626406

  19. Unremitting Cell Proliferation in the Secretory Phase of Eutopic Endometriosis

    PubMed Central

    Franco-Murillo, Yanira; Miranda-Rodríguez, José Antonio; Rendón-Huerta, Erika; Montaño, Luis F.; Cornejo, Gerardo Velázquez; Gómez, Lucila Poblano; Valdez-Morales, Francisco Javier; Gonzalez-Sanchez, Ignacio

    2014-01-01

    Objective: Endometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium. Design: Eutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle. Results: Expression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis. Conclusion: Unceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways. PMID:25194152

  20. Laparoscopic Imaging Techniques in Endometriosis Therapy: A Systematic Review.

    PubMed

    Vlek, Stijn L; Lier, M C I; Ankersmit, M; Ket, Johannes C F; Dekker, J J M L; Mijatovic, V; Tuynman, J B

    2016-01-01

    Endometriosis is a common disease associated with pelvic pain and subfertility. Laparoscopic surgical treatment has proven effective in endometriosis, but is hampered by a high rate of recurrence. The aim of this systematic review was to evaluate the intraoperative identification of endometriosis by enhanced laparoscopic imaging techniques, focusing on sensitivity and specificity. A systematic review was conducted according to PRISMA guidelines in PubMed, Embase, Cochrane Library, and Web of Science. Published prospective studies reporting on enhanced laparoscopic imaging techniques during endometriosis surgery were included. General study characteristics and reported outcomes, including sensitivity and specificity, were extracted. Nine studies were eligible for inclusion. Three techniques were described: 5-ALA fluorescence (5-ALA), autofluorescence (AFI), and narrow-band imaging (NBI). The reported sensitivity of 5-ALA and AFI for identifying endometriosis ranged from 91% to 100%, compared with 48% to 69% for conventional white light laparoscopy (WL). A randomized controlled trial comparing NBI + WL with WL alone reported better sensitivity of NBI (100% vs 79%; p < .001). All 9 studies reported an enhanced detection rate of endometriotic lesions with enhanced imaging techniques. Enhanced imaging techniques are a promising additive for laparoscopic detection and treatment of endometriosis. The 5-ALA, AFI, and NBI intraoperative imaging techniques had a better detection rate for peritoneal endometriosis compared with conventional WL laparoscopy. None of the studies reported clinical data regarding outcomes. Future studies should address long-term results, such as quality of life, recurrence, and need for reoperation.

  1. Developmental Exposure of Mice to TCDD Elicits a Similar Uterine Phenotype in Adult Animals as Observed in Women with Endometriosis

    PubMed Central

    Nayyar, Tultul; Bruner-Tran, Kaylon L.; Piestrzeniewicz-Ulanska, Dagmara; Osteen, Kevin G.

    2007-01-01

    Whether environmental toxicants impact an individual woman’s risk for developing endometriosis remains uncertain. Although the growth of endometrial glands and stroma at extra-uterine sites is associated with retrograde menstruation, our studies suggest that reduced responsiveness to progesterone may increase the invasive capacity of endometrial tissue in women with endometriosis. Interestingly, our recent studies using isolated human endometrial cells in short-term culture suggest that experimental exposure to the environmental contaminant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) can alter the expression of progesterone receptor isotypes. Compared to adult exposure, toxicant exposure during development can exert a significantly greater biological impact, potentially affecting the incidence of endometriosis in adults. To address this possibility, we exposed mice to TCDD at critical developmental time points and subsequently examined uterine progesterone receptor expression and steroid responsive transforming growth factor-β2 expression in adult animals. We find that the uterine phenotype of toxicant-exposed mice is markedly similarly to the endometrial phenotype of women with endometriosis. PMID:17056225

  2. Human alcohol-related neuropathology

    PubMed Central

    Kril, Jillian J.

    2015-01-01

    Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

  3. New developments in the medical treatment of endometriosis.

    PubMed

    Bedaiwy, Mohamed A; Alfaraj, Sukinah; Yong, Paul; Casper, Robert

    2017-03-01

    Endometriosis affects 1 in 10 women of reproductive-age. The current treatments are surgical and hormonal but have limitations, including the risk of recurrence, side effects, contraceptive action for women who desire pregnancy, and cost. New treatments include gonadotropin-releasing hormone analogues, selective progesterone (or estrogen) receptor modulators, aromatase inhibitors, immunomodulators, and antiangiogenic agents. Further research is needed into central sensitization, local neurogenesis, and the genetics of endometriosis to identify additional treatment targets. A wider range of medical options allows for the possibility of precision health and a more personalized treatment approach for women with endometriosis.

  4. Endometriosis after surgical menopause mimicking pelvic malignancy: surgeons' predicament.

    PubMed

    Bhat, Rani A; Teo, Melissa; Bhat, Akhil Krishnanand

    2014-05-01

    Prevalence of persistent endometriosis in women after menopause without any hormonal replacement therapy is very rare. This is a case of a woman with previous history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass, and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is the first case report with a unique mode of presentation wherein the patient presented with hemoperitoneum requiring emergency embolization of the vessel to stabilize the patient. She underwent en bloc resection of the tumor with high anterior resection of the rectum. Histopathology confirmed endometriosis.

  5. Endometriosis After Surgical Menopause Mimicking Pelvic Malignancy: Surgeons’ Predicament

    PubMed Central

    Bhat, Rani A.; Teo, Melissa; Bhat, Akhil Krishnanand

    2014-01-01

    Prevalence of persistent endometriosis in women after menopause without any hormonal replacement therapy is very rare. This is a case of a woman with previous history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass, and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is the first case report with a unique mode of presentation wherein the patient presented with hemoperitoneum requiring emergency embolization of the vessel to stabilize the patient. She underwent en bloc resection of the tumor with high anterior resection of the rectum. Histopathology confirmed endometriosis. PMID:24936277

  6. Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis.

    PubMed

    Bulun, Serdar E; Cheng, You-Hong; Pavone, Mary Ellen; Xue, Qing; Attar, Erkut; Trukhacheva, Elena; Tokunaga, Hideki; Utsunomiya, Hiroki; Yin, Ping; Luo, Xia; Lin, Zhihong; Imir, Gonca; Thung, Stephen; Su, Emily J; Kim, J Julie

    2010-01-01

    Loss of progesterone signaling in the endometrium may be a causal factor in the development of endometriosis, and progesterone resistance is commonly observed in women with this disease. In endometriotic stromal cells, the levels of progesterone receptor (PR), particularly the PR-B isoform, are significantly decreased, leading to a loss of paracrine signaling. PR deficiency likely underlies the development of progesterone resistance in women with endometriosis who no longer respond to progestin therapy. Here we review the complex epigenetic and transcriptional mechanisms leading to PR deficiency. The initial event may involve deficient methylation of the estrogen receptor (ER)beta promoter resulting in pathologic overexpression of ERbeta in endometriotic stromal cells. We speculate that alterations in the relative levels of ERbeta and ERalpha in endometrial tissue dictate E2-regulated PR expression, such that a decreased ERalpha-tauomicron-ERbeta ratio may result in suppression of PR. In this review, we propose a molecular model that may be responsible for changes in ERbeta and ERalpha leading to PR loss and progesterone resistance in endometriosis.

  7. Clinical Prediction of Deeply Infiltrating Endometriosis before Surgery: Is It Feasible? A Review of the Literature

    PubMed Central

    Mendonça Carneiro, Márcia; de Sousa Filogônio, Ivone Dirk; Pyramo Costa, Luciana Maria; de Ávila, Ivete; França Ferreira, Márcia Cristina

    2013-01-01

    Background. Endometriosis is a chronic benign gynecologic disease that can cause pelvic pain and infertility affecting almost 10% of reproductive-age women. Deeply infiltrating endometriosis (DIE) is a specific entity responsible for painful symptoms which are related to the anatomic location of the lesions. Definitive diagnosis requires surgery, and histological confirmation is advisable. The aim of this paper is to review the current literature regarding the possibility of diagnosing DIE accurately before surgery. Despite its low sensitivity and specificity, vaginal examination and evaluation of specific symptoms should not be completely omitted as a basic diagnostic tool in detecting endometriosis and planning further therapeutic interventions. Recently, transvaginal ultrasound (TVUS) has been reported as an excellent tool to diagnose DIE lesions in different locations (rectovaginal septum, retrocervical and paracervical areas, rectum and sigmoid, and vesical wall) with good accuracy. Conclusion. There are neither sufficiently sensitive and specific signs and symptoms nor diagnostic tests for the clinical diagnosis of DIE, resulting in a great delay between onset of symptoms and diagnosis. Digital examination, in addition to TVS, may help to gain better understanding of the anatomical extent and dimension of DIE which is of crucial importance in defining the best surgical approach. PMID:24089684

  8. cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis.

    PubMed

    Ahn, J I; Yoo, J-Y; Kim, T H; Kim, Y I; Ferguson, S D; Fazleabas, A T; Young, S L; Lessey, B A; Ahn, J Y; Lim, J M; Jeong, J-W

    2016-01-01

    Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.

  9. Human Relations Education Project. Final Evaluation Report.

    ERIC Educational Resources Information Center

    Buffalo Board of Education, NY.

    This project did the planning and pilot phases of an effort to improve the teaching of human relations in grades K-12 of public and private schools in the Buffalo-Niagara Falls metropolitan area. In the pilot phase, the project furnished on-the-job training for approximately 70 schools. The training was given by teams of human relations…

  10. Autoimmunity to endometrium and ovary in endometriosis.

    PubMed Central

    Mathur, S; Peress, M R; Williamson, H O; Youmans, C D; Maney, S A; Garvin, A J; Rust, P F; Fudenberg, H H

    1982-01-01

    Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:6759000

  11. Update on Biomarkers for the Detection of Endometriosis

    PubMed Central

    Fassbender, Amelie; Burney, Richard O.; O, Dorien F.; D'Hooghe, Thomas; Giudice, Linda

    2015-01-01

    Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium. PMID:26240814

  12. Endometriosis research using capture microdissection techniques: Progress and future applications

    PubMed Central

    Zhao, Luyang; Gu, Chenglei; Huang, Ke; Han, Weidong; Fu, Meng; Meng, Yuanguang

    2016-01-01

    Endometriosis is a common gynecological disease with high prevalence, while its etiology and pathophysiology have remained to be fully elucidated. Previous evidence suggested that this disorder may be in part or completely of somatic origin. However, traditional endometrial samples may not be ideal for investigation, as target cells, including epithelial and stromal cells, in endometriotic lesions are too sparse to be analyzed. Recently, capture microdissection techniques have been used to overcome these limitations and eliminate tissue heterogeneity in endometriosis research. Therefore, the present review summarized the alterations in epithelial and stromal cells in endometriosis tissues isolated through capture microdissection, outlined recent progress and provided directions for future investigation of the pathogenesis of endometriosis. PMID:27882213

  13. Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

    PubMed Central

    Tariverdian, Nadja; Theoharides, Theoharis C.; Siedentopf, Friederike; Gutiérrez, Gabriela; Jeschke, Udo; Rabinovich, Gabriel A.; Blois, Sandra M.

    2007-01-01

    Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis. PMID:17621704

  14. The actual role of robotics in the management of endometriosis.

    PubMed

    Cela, Vito; Obino, Maria E; Sergiampietri, Claudia; Simi, Giovanna; Papini, Francesca; Pinelli, Sara; Freschi, Letizia; Artini, Paolo G

    2017-03-07

    The advent of robot-assisted laparoscopy (RAL) represents an important innovation and has opened new perspectives for treatment of endometriosis, in particular in deep infiltrating endometriosis (DIE). RAL could offer several technical advantages in treating this complex disease, such as 3D vision, tremor filtration and better surgical ergonomy, would be able to improve surgical performances without increasing in surgical time, blood loss, intra- and postoperative complications and it reduces the rates of conversion to laparotomy. Additionally thanks to its reduced learning curve compared to conventional laparoscopy, facilitates the training of less experienced surgeons. For these reason DIE might be one of the best indications for robot assisted laparoscopy in gynecologic surgery. However, very few retrospective studies, small cases series and only a randomized clinical trial were reported. Further randomized control trial comparing CL to RAL for different stage of endometriosis and the different type of procedure performed would be mandatory in order to define potential benefits of RAL for endometriosis surgery.

  15. [Intrinsic ureteral endometriosis: description of a striking instance].

    PubMed

    Antonelli, Alessandro; Finotto, Elena; Zambolin, Tiziano; Fisogni, Simona; Simeone, Claudio

    2015-01-01

    Intrinsic ureteral endometriosis is a very rare condition. A 41 y. o. woman with right hydroureteronephrosis and other aspecific symptoms came to our attention. The CT scan showed an ureteral obstacle causing the hydroureteronephrosis. She underwent ureterorenoscopy with biopsies of the lesion that did not result to be diriment. Suspecting a ureteral neoplasm, the patient then underwent ureteral resection and ureterocystoneostomy, and the extemporary histological examination resulted as endometriosis. The abdominal exploration showed a parametrial and a peritoneal growth - both compatible with the extemporary histological examination - that were also excised. The post-operative course was uneventful. The definitive hystological examination confirmed the perioperatory diagnosis. Intrinsic ureteral endometriosis is confirmed as a rare pathology with an indefinite clinical presentation; its typical presentation, namely cyclic hematuria, seems to be an anecdotal feature. Therefore the diagnostics of intrinsic ureteral endometriosis is still difficult even despite such a striking presentation.

  16. Is cytochrome P450 3A4 regulated by menstrual cycle hormones in control endometrium and endometriosis?

    PubMed

    Piccinato, Carla A; Neme, Rosa M; Torres, Natália; Silvério, Renata; Pazzini, Vanessa Bitencourt; Rosa E Silva, Júlio C; Ferriani, Rui A

    2017-03-01

    The estrogen-metabolizing activities of cytochrome P450 (CYP) enzymes have been implicated in endometriosis. However, their regulation in various sources of endometrial tissue under different hormonal conditions has not been clarified. Our objective was to study the hormone regulation of a specific CYP enzyme, namely CYP3A4, in control (n = 15) and endometriosis patients (n = 42). To this end, we evaluated mRNA expression (using real-time PCR) of CYP3A4 in tissue samples classified according to the phase of menstrual cycle at which they were obtained as confirmed by the related circulating hormone levels. Protein expression was also evaluated by Western Blot. In order to further investigate the hormonal regulation of CYP3A4, stromal cells from ovarian endometriotic lesions were cultured with the prevailing hormones of the distinct phases of the menstrual cycle. We observed that all control and endometriosis tissues express CYP3A4. Nevertheless, changes in CYP3A4 gene expression related to cycle phase were only seen in the control eutopic endometrium and not in samples from endometriosis patients, with an increase in the luteal phase. Stromal cells isolated from ovarian endometriotic lesions expressed CYP3A4 and their exposure to luteal phase-mimicking hormones (estradiol + progesterone) reduced CYP3A4 mRNA in parallel with a diminished expression of the corresponding receptors, estrogen receptor alpha and progesterone receptor. Our findings suggest that steroid hormones are able to regulate CYP3A4 mRNA expression, although the circulating levels of these hormones can only regulate control endometrium and not endometriosis tissues, probably because of dysregulated local steroid concentration in these latter samples.

  17. [Endometriosis and genetics: what responsibility for the genes?].

    PubMed

    Borghese, B; Vaiman, D; de Ziegler, D; Chapron, C

    2010-05-01

    Endometriosis is a very frequent and debilitating disease responsible for a considerable socio-economic toll. In spite of that, its pathogenesis remains enigmatic. Endometriosis is hold for a multifactorial pathology resulting from the mixed effects of environmental and genetic factors. To date, few susceptibility factors have been reported, with the exception of some polymorphisms in estrogen and progesterone receptors. Large-scale expressional studies have clearly demonstrated that endometriosis is a hormone-dependant disease, characterized by three main features: (i) inflammation, (ii) excessive production of estrogens, and (iii) progesterone resistance. Endometriosis is also considered as a benign metastatic disease, closely linked to cancer. However, the risk of malignant transformation appears to be very limited, likely by a systematic repression of the genes involved in cell cycle and a specific regulation of the HOX genes. Lastly, endometriosis might result from abnormalities of the eutopic endometrium, which show the same molecular alterations than the ectopic endometrium, to a lesser extent however. These alterations, possibly occurring during the embryonic life through epigenetic and genetic predisposition, could lead to an earlier and non-invasive diagnosis for endometriosis.

  18. [Multidisciplinary approach for deep endometriosis: interests and organization].

    PubMed

    Dell'oro, M; Collinet, P; Robin, G; Rubod, C

    2013-01-01

    Deep endometriosis is a frequent disease that affects reproductive age women. This disease is characterized by the presence of functional endometrium-like tissue outside the uterus. The common sites of extragenital endometriosis are the bowel and the urinary tract. This disease is also associated with infertility. Furthermore, this disease can cause physical and psychological damage. Therefore, it is really important to develop a multidisciplinary approach in the aim to offer the appropriate treatment. The multidisciplinary team approach for endometriosis is developing to improve the understanding of endometriosis and a multidisciplinary committee for endometriosis was developed in our center. During this meeting, gynecologic, digestive surgeons, urologist, radiologist, procreative medical assistance physicians analyse the case. The role of surgery, before, after or as an alternative to in vitro fertilization (IVF) must be defined. The role of the medical treatment before or after the surgery, before the IVF shall be discussed in order to propose the optimal treatment. In fact, radical surgery is no more recommended and minimally invasive conservative surgery is encouraged in order to preserve the fertility. The multidisciplinary approach permits an appropriate optimal and personalised management of this multifocal disease. The multidisciplinary team approach helps in the development of evidence-based guidelines for the diagnosis and management of endometriosis.

  19. Hepatic endometriosis: a rare case and review of the literature.

    PubMed

    Liu, Kai; Zhang, Wei; Liu, Songyang; Dong, Bingfei; Liu, Yahui

    2015-04-04

    Hepatic endometriosis is one of the rarest disorders characterized by the presence of ectopic endometrium in the liver. To our knowledge, only 21 cases of hepatic endometrioma have been described in the medical literature. We report a case of a 36-year-old primiparous female with hepatic endometriosis forming a large cystic mass. The patient presented once with severe right quadrant pain as her only symptom and no history of endometriosis. Complete blood count and biochemical tests were normal. Abdominal ultrasonography and computed tomography scans suggested the presence of a 6.5 × 6.0 cm cystic mass in segment III of the liver. The mass was completely removed by local liver resection. The intraoperative frozen sections suggested a diagnosis of hepatic endometriosis. The diagnosis was confirmed through histological immunostaining without intrinsic abnormality. A preoperative diagnosis of hepatic endometriosis is made on the basis of considering the possibility in advance. Hepatic endometriosis should be considered in the differential diagnosis of a cystic liver mass despite conducting exhaustive investigations in the absence of characteristic clinical and radiological features. Histological examination is essential, and surgery remains the treatment of choice.

  20. Female sexual dysfunction in patients with endometriosis: Indian scenario

    PubMed Central

    Mishra, Vineet V.; Nanda, Sakshi; Gandhi, Khushali; Aggarwal, Rohina; Choudhary, Sumesh; Gondhali, Raveendra

    2016-01-01

    BACKGROUND: Female sexual dysfunction (FSD) in Indian women is often overlooked due to cultural beliefs and considered as social taboos. Sexuality is an important and integral part of life. There are many causes of sexual dysfunction, but the prevalence of FSD in endometriotic patients is still underdiagnosed. MATERIALS AND METHODS: Study design - Cross-sectional observational study conducted at tertiary care center, from June 2015 to March 2016. Sample size - Fifty-one patients in reproductive age group (18–47 years) who were diagnosed with endometriosis on diagnostic laparoscopy were included. Methods - FSD was assessed with a detailed 19-item female sexual function index questionnaire. All six domains of sexual dysfunction, i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain were studied. Exclusion - Patients with other gynecological, medical or surgical history were excluded. RESULTS: Out of 51 patients with endometriosis, 47.06% of patients had sexual dysfunction. With the increase in staging of endometriosis, sexual dysfunction prevalence is also rising. FSD was 100% in patients with severe endometriosis as compared to 33.33% in minimal endometriosis. CONCLUSION: Every individual deserves good sexual life. The sexual dysfunction associated with endometriosis should also be taken into consideration while managing these patients. PMID:28216913

  1. Can Platelet Indices Be New Biomarkers for Severe Endometriosis?

    PubMed Central

    Avcioğlu, Sümeyra Nergiz; Altinkaya, Sündüz Özlem; Küçük, Mert; Demircan-Sezer, Selda; Yüksel, Hasan

    2014-01-01

    Objective. The aim of this study was to investigate whether platelet indices-mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) would be useful as noninvasive biomarkers for determining the severity of endometriosis. Methods. A retrospective review of the medical charts of 164 patients diagnosed with endometriosis and who were operated on between 2001 and 2013 was performed. The stage of endometriosis was determined according to revised American Society for Reproductive Medicine criteria. Results. In patients with advanced endometriosis (Stages 3-4), PLT, PCT levels were found to be significantly higher and MPV, PDW values to be significantly lower when compared to initial endometriosis (Stages 1-2). In addition, there was a significant positive correlation between PLT (r: 0.800, P: 0.001) and PCT (r: 0.727, P: 0.002) and the inflammatory marker white blood cell count (WBC). Conclusion. Our finding may not sufficient for employing platelet indices solely in this differential diagnosis, but our finding could provide a suggestion for clinical physicians so that attention is paid to the value of platelet indices and that these may be taken into account when making decisions about the initial or advanced stages of endometriosis. PMID:25006484

  2. Decorin induced by progesterone plays a crucial role in suppressing endometriosis.

    PubMed

    Ono, Yoshihiro Joshua; Terai, Yoshito; Tanabe, Akiko; Hayashi, Atsushi; Hayashi, Masami; Yamashita, Yoshiki; Kyo, Satoru; Ohmichi, Masahide

    2014-11-01

    Dienogest, a synthetic progestin, has been shown to be effective against endometriosis, although it is still unclear as to how it affects the ectopic endometrial cells. Decorin has been shown to be a powerful endogenous tumor repressor acting in a paracrine fashion to limit tumor growth. Our objectives were to examine the direct effects of progesterone and dienogest on the in vitro proliferation of the human ectopic endometrial epithelial and stromal cell lines, and evaluate as to how decorin contributes to this effect. We also examined DCN mRNA expression in 50 endometriosis patients. The growth of both cell lines was inhibited in a dose-dependent manner by both decorin and dienogest. Using a chromatin immunoprecipitation assay, it was noted that progesterone and dienogest directly induced the binding of the decorin promoter in the EMOsis cc/TERT cells (immortalized human ovarian epithelial cells) and CRL-4003 cells (immortalized human endometrial stromal cells). Progesterone and dienogest also led to significant induced cell cycle arrest via decorin by promoting production of p21 in both cell lines in a dose-dependent manner. Decorin also suppressed the expression of MET in both cell lines. We confirmed that DCN mRNA expression in patients treated with dienogest was higher than that in the control group. In conclusion, decorin induced by dienogest appears to play a crucial role in suppressing endometriosis by exerting anti-proliferative effects and inducing cell cycle arrest via the production of p21 human ectopic endometrial cells and eutopic endometrial stromal cells.

  3. Unit on Human Feelings and Relations.

    ERIC Educational Resources Information Center

    Wellesley Public Schools, MA.

    The human relations units, intended especially for the benefit of slow learners who may have emotional problems but also valuable for other children, help students become more aware of the dynamics of intra and interpersonal relations. Emphasis is upon involving all class members in participation at their own level. Discussion of all common…

  4. Defining future directions for endometriosis research: workshop report from the 2011 World Congress of Endometriosis In Montpellier, France.

    PubMed

    Rogers, Peter A W; D'Hooghe, Thomas M; Fazleabas, Asgerally; Giudice, Linda C; Montgomery, Grant W; Petraglia, Felice; Taylor, Robert N

    2013-05-01

    Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.(1) A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.

  5. Bronchial Artery Embolization in the Management of Pulmonary Parenchymal Endometriosis with Hemoptysis

    SciTech Connect

    Kervancioglu, Selim Andic, Cagatay; Bayram, Nazan; Telli, Cumali; Sarica, Akif; Sirikci, Akif

    2008-07-15

    Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.

  6. [Moral aspects of human cloning and relations between humans].

    PubMed

    Lukow, P

    2001-01-01

    It is usually assumed that there is a strong logical relationship between traditional worldviews and attitudes towards human cloning. I argue that the association is contingent, which can be seen in the analysis of arguments of such leading bioethicists as G. J. Annas, H. Jonas, and J. A. Robertson. Traditional worldviews lack conceptual resources that would enable them to provide normative conclusions about cloning. It is therefore mistake to look to these traditional worldviews in search for moral instruction. Instead, one should appeal to knowledge of psychological and social aspects of human life, and in particular to the process of emotional ties which form relations between humans.

  7. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    PubMed Central

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N.; Nyholt, Dale R.; Morris, Andrew P.; Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G.; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T.; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B.; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G.; Bruinsma, Fiona; Kjaer, Susanne K.; Hildebrandt, Michelle A.T.; Liang, Dong; Lu, Karen H.; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A.; Cramer, Daniel W.; Terry, Kathryn L.; Tworoger, Shelley S.; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Brooks-Wilson, Angela; Olson, Sara H.; McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.; Cook, Linda S.; Le, Nhu D.; Gilks, C. Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P.; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R.; Narod, Steven A.; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J.; Wu, Anna H.; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M.; Fridley, Brooke L.; Winham, Stacey J.; Bandera, Elisa V.; Poole, Elizabeth M.; Morgan, Terry K.; Risch, Harvey A.; Goode, Ellen L.; Schildkraut, Joellen M.; Webb, Penelope M.; Pearce, Celeste L.; Berchuck, Andrew; Pharoah, Paul D.P.; Montgomery, Grant W.; Zondervan, Krina T.; Chenevix-Trench, Georgia; MacGregor, Stuart

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18–0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07–0.89 and 0.40, 95% CI = 0.05–0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11–0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci. PMID:26231222

  8. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer.

    PubMed

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N; Nyholt, Dale R; Morris, Andrew P; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Gilks, C Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Risch, Harvey A; Goode, Ellen L; Schildkraut, Joellen M; Webb, Penelope M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Montgomery, Grant W; Zondervan, Krina T; Chenevix-Trench, Georgia; MacGregor, Stuart

    2015-10-15

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

  9. Non–Dioxin-Like Polychlorinated Biphenyls and Risk of Endometriosis

    PubMed Central

    Trabert, Britton; De Roos, Anneclaire J.; Schwartz, Stephen M.; Peters, Ulrike; Scholes, Delia; Barr, Dana B.; Holt, Victoria L.

    2010-01-01

    Background Endometriosis, a gynecologic disorder affecting 8–10% of reproductive-age women in the United States, is defined as the presence of endometrial tissue outside the uterus and is linked to pelvic pain and infertility. Environmental contaminants, including polychlorinated biphenyls (PCBs), are hypothesized to contribute to endometriosis risk through effects on steroid hormones. Objective We evaluated serum concentrations of certain noncoplanar PCBs, which have no or only weak dioxin-like properties, as risk factors for endometriosis. Methods In a case–control study of Group Health enrollees in western Washington State, 20 PCB congeners were measured in serum from surgically confirmed endometriosis cases that were newly diagnosed between 1996 and 2001 (n = 251) and from female controls matched for age and reference year (n = 538). Results Summed and estrogenic PCB concentrations were not associated with endometriosis risk [summed: odds ratio (OR) = 1.3; 95% confidence interval (CI), 0.8–2.2; estrogenic: OR = 1.1; 95% CI, 0.8–1.4]. Although several congener-specific ORs were statistically above or below the null (PCB 170: third quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.9; PCB 196: third quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7; PCB 201: second vs. lowest: OR = 0.5; 95% CI, 0.3–0.8; third quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7), there were no overall consistent patterns of endometriosis risk. Conclusions Taken in context with other North American studies, our findings suggest that noncoplanar PCB concentrations consistent within the range of exposure currently observed in western Washington State do not contribute meaningfully to endometriosis risk. PMID:20423815

  10. Human Intergroup Relations. Certification Requirement #69.

    ERIC Educational Resources Information Center

    Northcentral Technical Coll., Wausau, WI.

    This document provides materials for a course in human intergroup relations for preservice or inservice teachers preparing to work with a diverse, disadvantaged group of students. The information in the guide is drawn from the faculty and student support staff of Northcentral Technical College (NTC) in Wausau, Wisconsin, which serves a variety of…

  11. Relational Human Ecology: Reconciling the Boundaries of Humans and Nature

    NASA Astrophysics Data System (ADS)

    McNiel, J.; Lopes, V. L.

    2010-12-01

    Global change is transforming the planet at unprecedented rates. Global warming, massive species extinction, increasing land degradation, overpopulation, poverty and injustice, are all the result of human choices and non-sustainable ways of life. What do we have to do and how much do we have to change to allow a transition to a more ecologically-conscious and just society? While these questions are of central concern, they cannot be fully addressed under the current paradigm, which hinders both our collection of knowledge and derivation of solutions. This paper attempts to develop a new variant of ecological thinking based on a relational ontological/epistemological approach. This is offered as a foundation for the political initiative to strive for a more fulfilling, sustainable and just society. This new approach, theoretically conceptualized as ‘relational human ecology,’ offers a relational (holistic) framework for overcoming mechanistic thinking and exploring questions regarding the long-term attainment of sustainability. Once established, we illustrate how the relational framework offers a new holistic approach centered on participatory inquiry within the context of a community workshop. We conclude with discussing possible directions for future relational human ecological participatory research, conducted from the intersection of myriad participants (i.e. agencies, academics, and community residents), and the ways in which this will allow for the derivation of accurate and sustainable solutions for global change. Key words: relational thinking, human ecology, complex adaptive systems, participatory inquiry, sustainability Vicente L. Lopes (corresponding author) Department of Biology Texas State University San Marcos, TX, USA e-mail: vlopes@txstate.edu Jamie N. McNiel Department of Sociology Texas State University San Marcos, TX, USATable 2 - Comparing Orthodox versus Relational Approaches to Ecological Inquiry * Retroduction, logical reasoning that

  12. High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status.

    PubMed

    Heard, Melissa E; Melnyk, Stepan B; Simmen, Frank A; Yang, Yanqing; Pabona, John Mark P; Simmen, Rosalia C M

    2016-07-01

    Endometriosis is a benign gynecological condition that causes considerable morbidity due to associated infertility, debilitating pelvic pain and inflammatory dysfunctions. Diet is a highly modifiable risk factor for many chronic diseases, but its contribution to endometriosis has not been extensively investigated, due partly to the paradoxical inverse association between obesity and disease incidence. Nevertheless, chronic exposure to dietary high-fat intake has been linked to greater systemic inflammation and oxidative stress, both features of women with endometriosis. Here, we evaluated the effects of a high-fat diet (HFD) (45% fat kcal) on endometriosis progression using an immunocompetent mouse model where ectopic lesion incidence was induced in wild-type recipients by ip administration of endometrial fragments from transcription factor Krüppel-like factor 9-null donor mice. We show that HFD significantly increased ectopic lesion numbers in recipient mice with no significant weight gain and modifications in systemic ovarian steroid hormone and insulin levels, relative to control diet-fed (17% fat kcal) mice. HFD promotion of lesion establishment was associated with reductions in stromal estrogen receptor 1 isoform and progesterone receptor expression, increased F4/80-positive macrophage infiltration, higher stromal but not glandular epithelial proliferation, and enhanced expression of proinflammatory and prooxidative stress pathway genes. Lesion-bearing HFD-fed mice also displayed higher peritoneal fluid TNFα and elevated local and systemic redox status than control diet-fed counterparts. Our results suggest that HFD intake exacerbates endometriosis outcome in the absence of ovarian dysfunction and insulin resistance in mice and warrants further consideration with respect to clinical management of endometriosis progression and recurrence in nonobese patients.

  13. Role of Shigella infection in endometriosis: a novel hypothesis.

    PubMed

    Kodati, V L; Govindan, S; Movva, S; Ponnala, S; Hasan, Q

    2008-01-01

    Endometriosis is the presence of endometrial cells and stroma at ectopic sites outside the uterine cavity. The natural history of endometriosis is uncertain, its etiology unknown, the clinical presentation inconsistent, diagnosis difficult and the treatment poorly standardized. It causes significant morbidity due to pelvic pain and infertility among 15-25% of women during their reproductive age. The benign disease causes peritoneal inflammation, fibrosis, adhesions and ovarian cysts but displays features of malignancy, like neo-vascularization, local invasion and distant metastasis. Mechanical, hormonal, immunological, environmental and genetic factors have been implicated in its etiology but provide inconclusive explanations. Present study was carried out on ectopic and eutopic endometriotic tissue specimens collected during laproscopy/laprotomy from cases of endometriosis. mRNA was isolated from the tissues and converted to cDNA by RT and subsequently subjected to differential display Polymerase Chain Reaction using seven sets of arbitrary primers. A unique band was identified only in the ectopic endometriotic tissue, which was sequenced. BLAST search results revealed sequence homology to shigella bacterial DNA leading us to hypothesize that infection may be playing a role in the etiology of endometriosis. This is the first report implicating the role of bacterial infection in the etiology of endometriosis. Shigella is known to invade the mucosa of the colon through the feco-oral route causing Shigellosis. The pathogenesis of shigellosis involves inflammation, ulceration, haemorrhage, tissue destruction and fibrosis of the colonic mucosa resulting in abdominal pain and diarrhoea/dysentery, this is similar to the pathogenesis of endometriosis which also involves inflammation, haemorrhage, tissue destruction and fibrotic adhesions of the pelvic peritoneum resulting in abdominal pain and infertility. The non-motile shigella bacteria invade the deeper mucosal layers

  14. Medical Treatments for Endometriosis-Associated Pelvic Pain

    PubMed Central

    Luppi, Stefania; Ricci, Giuseppe

    2014-01-01

    The main sequelae of endometriosis are represented by infertility and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic impact. In the last decades, an impressive amount of pharmacological agents have been tested for the treatment of endometriosis-associated pelvic pain. However, only a few of these have been introduced into clinical practice. Following the results of the controlled studies available, to date, the first-line treatment for endometriosis associated pain is still represented by oral contraceptives used continuously. Progestins represent an acceptable alternative. In women with rectovaginal lesions or colorectal endometriosis, norethisterone acetate at low dosage should be preferred. GnRH analogues may be used as second-line treatment, but significant side effects should be taken into account. Nonsteroidal anti-inflammatory drugs are widely used, but there is inconclusive evidence for their efficacy in relieving endometriosis-associated pelvic pain. Other agents such as GnRH antagonist, aromatase inhibitors, immunomodulators, selective progesterone receptor modulators, and histone deacetylase inhibitors seem to be very promising, but there is not enough evidence to support their introduction into routine clinical practice. Some other agents, such as peroxisome proliferator activated receptors-γ ligands, antiangiogenic agents, and melatonin have been proven to be efficacious in animal studies, but they have not yet been tested in clinical studies. PMID:25165691

  15. Non-thermal plasma prevents progression of endometriosis in mice.

    PubMed

    Ishida, Chiharu; Mori, Masahiko; Nakamura, Kae; Tanaka, Hiromasa; Mizuno, Masaaki; Hori, Masaru; Iwase, Akira; Kikkawa, Fumitaka; Toyokuni, Shinya

    2016-10-01

    Endometriosis is observed in ∼10% of reproductive age women. Ovarian endometriosis not only causes dysmenorrhea but also causes infertility and a high risk of adenocarcinoma. Due to its scattered nature, complete surgical resection is difficult. Endometriosis consists of glandular and stromal cells. Previously, we showed that endometrial stromal cells (ESCs) play a role in the protection against pathologic events caused by monthly repeated hemorrhage. Here, we undertook a preclinical study of non-thermal plasma (NTP) as a surgical treatment of endometriosis. Epithelial cells were most sensitive to NTP-activated medium in vitro, whereas ectopic ESCs were most resistant. We then transplanted excised uteruses into BALB/c mice from donors of the same strain with estradiol supplementation. Four weeks after the transplantation, we exposed NTP to each endometriotic lesion after laparotomy. Immunohistochemical analysis revealed that immediately after NTP exposure, epithelial cells exhibited significantly higher levels of nuclear immunostaining for 8-hydroxy-2'-deoxyguanosine than did stromal cells. Four weeks after NTP exposure, the total surface area consisting of endometriotic cysts was significantly smaller with less epithelial proliferative activity than the helium-exposed control, whereas the number of endometriotic lesions had not changed. Therefore, NTP exposure may be useful to prevent the progression and recurrence of endometriosis.

  16. Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment

    PubMed Central

    Mendiola, Jaime; Sánchez-Ferrer, María L.; Jiménez-Velázquez, Raquel; Cánovas-López, Laura; Hernández-Peñalver, Ana I.; Corbalán-Biyang, Shiana; Carmona-Barnosi, Ana; Prieto-Sánchez, María T.; Nieto, Aníbal; Torres-Cantero, Alberto M.

    2016-01-01

    STUDY QUESTION Is the length of the anogenital distance (AGD), a biomarker of the in-utero prenatal hormonal environment, associated with the presence of endometriomas and deep infiltrating endometriosis (DIE)? SUMMARY ANSWER Shorter AGD is associated with presence of endometriomas and DIE. WHAT IS KNOWN ALREADY It is debated whether hormonal exposure to estrogens in utero may be a risk factor for endometriosis in adulthood. AGD is a biomarker of prenatal hormonal environment and observational studies have shown an association between AGD and reproductive parameters in both sexes. STUDY DESIGN, SIZE, DURATION This case–control study of 114 women with endometriosis (endometriomas and/or DIE) and 105 controls was conducted between September 2014 and May 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS Cases were attending the Endometriosis Unit of the Hospital. Prevalent as well as incident cases, diagnosed by transvaginal ultrasound (TVUS), were included. Controls were women without endometriosis attending the gynecological outpatient clinic for routine gynecological exams. Participants completed health questionnaires, followed physical and gynecological examinations, including TVUS. Measurements from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF) were obtained in all subjects. Unconditional multiple logistic regression was used to estimate the association between AGD measurements and presence of endometriomas and/or DIE while accounting for important confounders and covariates, including age, body mass index, vaginal delivery or episiotomy. MAIN RESULTS AND THE ROLE OF CHANCE AGDAF was related to presence of endometriomas and/or DIE. For all cases of endometriosis (endometriomas and DIE), women in the lowest tertile of the AGDAF distribution, compared with the upper tertile, were 7.6-times (95% CI 2.8–21.0; P-trend < 0.001) more likely to have endometriosis. With

  17. Successful pregnancy after excision of cesarean scar endometriosis with uterovesicocutaneous fistula: A rare case report

    PubMed Central

    Juneja, Sunil Kumar; Tandon, Pooja; Chopra, Isha

    2016-01-01

    Scar endometriosis is an infrequent type of extrapelvic endometriosis. The most common extrapelvic form of endometriosis is cutaneous endometriosis, involving scar tissues occurring after obstetric or gynecologic procedures such as episiotomy, hysterotomy, cesarean section, and even laparoscopic surgery. The clinical presentation of scar endometriosis, i.e., tender swellings, mimics other dermatological and/or surgical conditions and delays the diagnosis. Scar endometriosis very rarely can get complicated with uterocutaneous fistula with a reported incidence of very few cases in world literature. We report a case of a 36-year-old woman presenting with scar endometriosis with complicated uterocutaneous fistula 11 years after her last lower segment cesarean section, managed successfully with laparotomy-fistulectomy and sleeve resection of the bladder with repair followed by successful subsequent spontaneous conception and pregnancy terminated by lower segment cesarean section. PMID:27857904

  18. Is abnormal eutopic endometrium the cause of endometriosis? The role of eutopic endometrium in pathogenesis of endometriosis

    PubMed Central

    Liu, Haiyuan; Lang, Jing He

    2011-01-01

    Summary Endometriosis (EM) is one of the most common diseases which severely affect the health and reproductive function of women of childbearing age. There are fundamental abnormal changes within the eutopic endometrium of women with endometriosis compared to normal endometrium of women without endometriosis. Eutopic endometrium shows enhanced ability of proliferation, implantation and angiogenesis, and greater probability of escaping the unfavorable conditions of the ectopic environment. Therefore, the character of eutopic endometrium determines the fate of the backward-flowing endometrial tissue – to live or to die. The abnormal endometrial tissue in EM patients flows backward to the pelvic cavity, completing a 3-step procedure of pathogenesis (attachment-aggression-angiogenesis), and ultimately develops into EM. Abnormal eutopic endometrium may also play important roles in endometriosis-associated infertility. This recognition regarding the pathogenesis of endometriosis ultimately will help to discover new methods for diagnosis and treatment. Endometrial markers for micro-invasive diagnosis and direct treatment of eutopic endometrium as the origin of the disease should be further investigated. PMID:21455119

  19. Two Young Women with Left-sided Pneumothorax Due to Thoracic Endometriosis

    PubMed Central

    Yukumi, Shungo; Suzuki, Hideaki; Morimoto, Masamitsu; Shigematsu, Hisayuki; Okazaki, Mikio; Abe, Masahiro; Kitazawa, Sohei; Nakamura, Kenji; Sano, Yoshifumi

    2016-01-01

    Pneumothorax associated with thoracic endometriosis (TE) generally occurs in women around 30 years old and it usually affects the right pleural cavity. We herein report two cases of TE associated with left-sided pneumothorax in young women. The prevalence of TE in younger patients may be underestimated if these cases are treated as spontaneous pneumothorax. Pneumothorax occurring in younger patients has not been reported to show laterality. TE-related or catamenial pneumothorax in young women must therefore represent a different clinical entity from the condition seen in older patients. PMID:27904115

  20. Progesterone resistance in a baboon model of endometriosis.

    PubMed

    Fazleabas, Asgerally T

    2010-01-01

    The development of a baboon model of induced endometriosis, which recapitulates the retrograde menstruation hypothesis, has greatly facilitated our understanding of the early events associated with the disease process. Sequential analysis of the eutopic endometrium following the establishment of disease suggests that the development of progesterone resistance is a gradual process and becomes evident after 6 months of disease induction. This resistance is manifested by a decreased responsiveness of the progesterone receptor and its chaperone immunophilins as well as epigenetic modifications of progesterone-regulated genes. In comparative studies, the time-dependent changes observed in the baboon eutopic endometrium are similar to those that have been reported to be altered in women with endometriosis. The baboon model therefore provides insight into the potential mechanisms by which genes in the eutopic endometrium are dysregulated and how this alteration results in infertility that is associated with endometriosis.

  1. Widespread endometriosis mimicking ovarian malignancy: a case report.

    PubMed

    Akinola, R A; Akinola, O I; Alakija, A; Wright, K O

    2012-03-01

    A 26 year old Nigerian nulliparous woman who presented in the medical emergency unit of a teaching hospital was referred after two weeks of management to the gynecology casualty with a diagnosis of malignant left ovarian cyst, because of the ascites, massive haemorrhagic pleural effusion, a left ovarian mass and an elevated C-125 marker. However, exploratory laparotomy, cytologic and histological examination of the pleural fluid and biopsied specimens revealed endometriosis. We present a case of intra and extra-pelvic endometriosis which simulated a malignant ovarian lesion and was histologically confirmed by cytology of the haemorrhagic pleural effusion and biopsy of the ovarian mass and peritoneal deposits obtained at laparotomy. This is to draw the attention of clinicians to endometriosis as a cause of pleural effusion, ascites and groin swelling which can simulate ovarian cancer.

  2. Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways

    PubMed Central

    Taylor, Robert N.; Kane, Maureen A.; Sidell, Neil

    2016-01-01

    Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/ or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease. PMID:26132929

  3. Endometriosis mimicking glandular atypia in a cervical cytology

    PubMed Central

    Rodriguez–Urrego, Paula A; Dulcey–Hormiga, Isabel C; Barrera–Herrera, Luis E; Suarez–Zamora, David A; Palau–Lazaro, Mauricio A; Buritica–Cifuentes, Catalina

    2017-01-01

    Endometriosis involving the uterine cervix is a rare condition that can lead to diagnostic errors in the interpretation of Pap smear. We report the case of a 41-year-old patient in whom the initial Pap smear revealed three-dimensional clusters of glandular cells with elongated nuclei, occasional mitosis, and atypia, which was interpreted as atypical glandular cells, not otherwise specified (NOS). The patient was taken to colposcopy and endocervical biopsy. Colposcopy was normal and the biopsy presented glands with elongated nuclei and surrounded by endometrial stroma admixed with normal endocervical glands. Immunohistochemical studies were reactive for CD10 in the stromal cells and vimentin in endometrioid glands. The findings were consistent with cervical endometriosis. Endometriosis in the cervix is an uncommon pathology that mimics malignancy and may be interpreted as atypical or glandular neoplasia in the cytology. PMID:28182083

  4. RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis.

    PubMed

    Guo, Cuishan; Ren, Fang; Wang, Danbo; Li, Yan; Liu, Kuiran; Liu, Shuang; Chen, Peng

    2014-12-01

    The aim of the present study was to investigate the role of epigenetic inactivation of the runt-related transcription factor 3 gene (RUNX3) in the malignant transformation of ovarian endometriosis. Samples obtained by microdissection and scraping included 30 malignant ovarian endometriotic cyst tissues and 30 corresponding eutopic endometrium tissues from the endometriosis-associated ovarian carcinoma (EAOC) group, 19 benign ovarian endometriotic cyst tissues and 22 corresponding eutopic endometrium tissues from the endometriosis (EM) group and 22 normal eutopic endometrium tissues from the control endometrium (CE) group. RUNX3 methylation status was determined by methylation-specific PCR and bisulfite sequencing, while levels of RUNX3 and ERα protein expression were evaluated using immunohistochemistry. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the malignant ovarian endometriotic cysts from the EAOC group was significantly higher than that in the benign ovarian endometriotic cysts from the EM group. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the eutopic endometrium from the EAOC group was significantly higher than that in the EM and CE groups. An inverse correlation between positive RUNX3 protein expression and methylation was observed and a positive correlation was shown between RUNX3 methylation and ERα protein expression. In the malignant ovarian endometriotic cysts from the EAOC group, there was no significant correlation between methylation frequency of the RUNX3 gene and histological type. However, the percentage of RUNX3 gene methylation was significantly higher in the tissue samples from patients with surgical stage IC EAOC than the percentage in patients with stage IA and IB disease. These results suggest that RUNX3 inactivation by promoter hypermethylation plays a role in the progression of malignant transformation of ovarian EM and is closely related to estrogen metabolism. Negative

  5. Morphologic features of endometriosis in various types of cytologic specimens.

    PubMed

    Barkan, Güliz A; Naylor, Bernard; Gattuso, Paolo; Küllü, Sevgi; Galan, Kristine; Wojcik, Eva M

    2013-11-01

    Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. This study evaluates the cytomorphologic features of endometriosis in various cytologic specimen types [fine-needle aspiration (FNA), effusion cytology (EF), touch imprint (ToP), and cervical smear (PAP)], and assesses the key elements helpful in recognizing this lesion. A total of 18 cases (8 FNA, 4 EF, 5 ToP, and 1 PAP) of cytologically diagnosed and histologically/clinically confirmed endometriosis diagnosed between 1988 and 2006 comprises the material for this study. The morphologic features evaluated of the three components included: cellularity, presence of sheets of glandular cells, three-dimensional (3D) glandular clusters, tubular structures, single cells, syncytial groups of stromal cells, stromal cells entrapped within basement membrane (BM)-like material, cytologic atypia, presence of mitotic figures, and hemosiderin-laden histiocytes. Endometrial glands, stroma, and hemosiderin-laden histiocytes were all identified in 14/18 (77.8%) cases. FNA specimens were more cellular than that of both EF and ToP specimens. Tubular structures, 3D glandular clusters, stromal cells entrapped in BM and syncytial stromal groups were more common in FNAs, and ToPs compared with the EFs. The ratio of the endometrial glandular and stromal cells was similar in all specimen types. Atypia and mitotic figures were rarely encountered. Diagnosis of endometriosis could be made independently on either smears/ThinPrep(™) slides or on cell blocks in all cases where these preparations were available. On follow up, none of the patients developed malignancy. Endometriosis can be reliably and safely diagnosed in various cytologic materials. Cytologic atypia is uncommon. Components of endometriosis could show minor morphologic alterations in different specimen types.

  6. Morphologic features of endometriosis in various types of cytologic specimens.

    PubMed

    Barkan, Güliz A; Naylor, Bernard; Gattuso, Paolo; Küllü, Sevgi; Galan, Kristine; Wojcik, Eva M

    2013-03-20

    Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. This study evaluates the cytomorphologic features of endometriosis in various cytologic specimen types [fine-needle aspiration (FNA), effusion cytology (EF), touch imprint (ToP), and cervical smear (PAP)], and assesses the key elements helpful in recognizing this lesion. A total of 18 cases (8 FNA, 4 EF, 5 ToP, and 1 PAP) of cytologically diagnosed and histologically/clinically confirmed endometriosis diagnosed between 1988 and 2006 comprises the material for this study. The morphologic features evaluated of the three components included: cellularity, presence of sheets of glandular cells, three-dimensional (3D) glandular clusters, tubular structures, single cells, syncytial groups of stromal cells, stromal cells entrapped within basement membrane (BM)-like material, cytologic atypia, presence of mitotic figures, and hemosiderin-laden histiocytes. Endometrial glands, stroma, and hemosiderin-laden histiocytes were all identified in 14/18 (77.8%) cases. FNA specimens were more cellular than that of both EF and ToP specimens. Tubular structures, 3D glandular clusters, stromal cells entrapped in BM and syncytial stromal groups were more common in FNAs, and ToPs compared with the EFs. The ratio of the endometrial glandular and stromal cells was similar in all specimen types. Atypia and mitotic figures were rarely encountered. Diagnosis of endometriosis could be made independently on either smears/ThinPrep(™) slides or on cell blocks in all cases where these preparations were available. On follow up, none of the patients developed malignancy. Endometriosis can be reliably and safely diagnosed in various cytologic materials. Cytologic atypia is uncommon. Components of endometriosis could show minor morphologic alterations in different specimen types. Diagn. Cytopathol. 2013. © 2013 Wiley Periodicals, Inc.

  7. [Interest of selective progesterone receptor modulators in endometriosis].

    PubMed

    Merviel, P; Lourdel, E; Sanguin, S; Gagneur, O; Cabry, R; Nasreddine, A

    2013-09-01

    The SPRM (selective progesterone receptor modulators) are agonists and/or antagonists of progesterone receptor. They are responsible for anovulation, amenorrhea and a lower prostaglandin levels, which leads to an improvement in pain and regression of lesions in endometriosis. On the endometrium, a particular aspect, the progesterone receptor modulator-associated endometrial changes (PAEC), raises additional studies to verify its harmlessness. However, due to the lack of hypoestrogenism and metabolic effects with these drugs, it is very likely that the SPRM will in the near future an important place in the treatment of endometriosis.

  8. Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age

    PubMed Central

    Porpora, Maria Grazia; Medda, Emanuela; Abballe, Annalisa; Bolli, Simone; De Angelis, Isabella; di Domenico, Alessandro; Ferro, Annamaria; Ingelido, Anna Maria; Maggi, Antonella; Panici, Pierluigi Benedetti; De Felip, Elena

    2009-01-01

    Background Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. Objective We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. Methods We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. Results We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs. Conclusions The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis. PMID:19654915

  9. Peritoneal Fluid From Infertile Women With Minimal/Mild Endometriosis Compromises the Meiotic Spindle of Metaphase II Bovine Oocytes.

    PubMed

    Gazeto Melo Jianini, Bruna Talita; Giorgi, Vanessa Silvestre Innocenti; Da Broi, Michele Gomes; de Paz, Cláudia Cristina Paro; Rosa E Silva, Júlio César; Ferriani, Rui Alberto; Navarro, Paula Andrea

    2017-01-01

    Some studies have demonstrated alterations in the composition of peritoneal fluid (PF) from women with endometriosis. Controversial studies have suggested that impaired oocyte quality may be involved in the pathogenesis of endometriosis-related infertility. The aim of this study was to evaluate the spindle and chromosome distribution of in vitro-matured oocytes in the presence of 2 concentrations of PF from infertile women with minimal/mild endometriosis (EI/II) compared to fertile controls. We performed an experimental study using a bovine model. Samples of PF were obtained from 12 women who underwent videolaparoscopy-6 infertile women with EI/II and 6 fertile women without endometriosis (control group). Immature bovine oocytes underwent in vitro maturation (IVM) in the absence of PF and in the presence of 2 concentrations (1% and 10%) of PF from fertile women and from infertile women with EI/II. After 22 to 24 hours of IVM, oocytes were fixed for subsequent immunofluorescence staining for the visualization of microtubules and chromosomes by confocal microscopy. The percentage of meiotically normal oocytes was significantly lower for oocytes that underwent IVM in the presence of 1% (62.50%) and 10% (56.25%) of PF from infertile women with EI/II than in the absence of PF (88.46%) and in the presence of 1% (78.57%) and 10% (84.61%) of PF from fertile women ( P < .01). We demonstrated that PF from infertile women with EI/II promotes meiotic abnormalities in in vitro-matured bovine oocytes. Therefore, our results contribute to the understanding of the etiopathogenic mechanisms of infertility related to EI/II.

  10. Endometriosis impairs bone marrow-derived stem cell recruitment to the uterus whereas bazedoxifene treatment leads to endometriosis regression and improved uterine stem cell engraftment.

    PubMed

    Sakr, Sharif; Naqvi, Hanyia; Komm, Barry; Taylor, Hugh S

    2014-04-01

    Endometriosis is a disease defined by the ectopic growth of uterine endometrium. Stem cells contribute to the generation of endometriosis as well as to repair and regeneration of normal endometrium. Here we demonstrate that the selective estrogen receptor modulator bazedoxifene (BZA), administered with conjugated estrogens (CEs), leads to regression of endometriosis lesions as well as reduction in stem cell recruitment to the lesions. Female mice underwent transplantation of male bone marrow. Endometrium was transplanted in the peritoneal cavity of half to create experimental endometriosis. Mice with or without experimental endometriosis were randomized to BZA/CE or vehicle treatment. Endometriosis lesions, bone marrow-derived mesenchymal stem cell engraftment of the lesions, and eutopic endometrium as well as ovarian stimulation were assessed. BZA treatment significantly reduced lesion size, gland number, and expression of proliferation marker proliferating cell nuclear antigen. Ovarian weight was not affected. Stem cells were recruited to the endometriosis lesions, and this recruitment was dramatically reduced by BZA/CE treatment. Stem cell engraftment was reduced in the uterus of animals with endometriosis; however the number of stem cells engrafting the uterus was completely restored by treatment with BZA/CE. Competition between endometriosis and the eutopic endometrium for a limited supply of stem cells and depletion of normal stem cells flux to the uterus is a novel mechanism by which endometriosis interferes with endometrial function and fertility. BZA/CE not only treats lesions of endometriosis, it also dramatically reduces stem cell recruitment to the lesions and restores stem cell engraftment of the uterine endometrium.

  11. Improved clinical outcomes of patients with ovarian carcinoma arising in endometriosis

    PubMed Central

    Zhou, Jiayi; Lu, Yingying; Wang, Zehua; Liu, Haiou; Xu, Congjian

    2017-01-01

    Background Despite enormous efforts to dissect the role of endometriosis in ovarian cancer development, the difference in prognosis between ovarian cancer patients with or without endometriosis remains elusive. The purpose of this study is to assess the association between endometriosis and the prognosis in patients with ovarian cancer. Results Ovarian cancer arising in endometriosis tended to be presented as clear cell histology, early stage, less intraperitoneal metastasis and ascites, and lower CA125 level compared with those without endometriosis. Multivariate Cox regression analysis identified endometriosis as an independent prognostic factor for progression free survival (P = 0.002) and overall survival (P = 0.009) in all patients and especially for early stage. A nomogram integrating endometriosis, FIGO stage and CA125 was established to predict progression free survival and overall survival. Materials and methods This study retrospectively enrolled 196 ovarian cancers arising or not in endometriosis judged by adjunctive use of CD10 immunohistochemistry in conjunction with H&E staining specimens. Clinicopathologic variables, progression-free survival (PFS) and overall survival (OS) were recorded. Kaplan-Meier analysis was performed to compare survival curves. Cox regression models were used to analyze the effect of endometriosis on PFS and OS. A prognostic nomogram was constructed based on the independent prognostic factors identified by multivariate analysis. Conclusions Endometriosis is an independent predictor of prognosis in ovarian cancer patients. PMID:27992377

  12. Relational and Transcendental Humanism: Exploring the Consequences of a Thoroughly Pragmatic Humanism

    ERIC Educational Resources Information Center

    Hansen, James T.

    2007-01-01

    The relational and transcendental elements of humanism are considered. Although the relational component of humanism is extraordinarily valuable, the author argues that the transcendental portion of humanism should be abandoned. The implications of a thoroughly pragmatic humanism are explored.

  13. Polymorphism of the progesterone receptor gene associated with endometriosis in patients from Goiás, Brazil.

    PubMed

    Costa, I R; Silva, R C P C; Frare, A B; Silva, C T X; Bordin, B M; Souza, S R; Ribeiro Júnior, C L; Moura, K K V O

    2011-07-06

    We investigated a possible link between endometriosis and polymorphism of the progesterone receptor gene (PROGINS). The endometriosis group consisted of 54 patients with a diagnosis of endometriosis by laparoscopy, and the control group comprised 44 women without endometriosis. Genotypes for PROGINS polymorphisms (A1/A1, A1/A2 and A2/A2) were determined by polymerase chain reaction and analyzed on a 2% agarose gel stained with ethidium bromide. The frequency of polymorphic genotypes (A1/A2 and A2/A2) was significantly higher in patients with endometriosis (33%) than in the control group (16%). We conclude that there is a significant correlation between PROGINS polymorphism and endometriosis.

  14. A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

    PubMed Central

    Becker, Christian M.; Wright, Renee D.; Satchi-Fainaro, Ronit; Funakoshi, Tae; Folkman, Judah; Kung, Andrew L.; D’Amato, Robert J.

    2006-01-01

    Endometriosis, the presence of ectopic endometrial tissue, is a common disease associated with high morbidity and socioeconomic problems. Angiogenesis, the formation of new blood vessels, plays an important role in the formation and growth of endometriotic lesions. We have created a novel, noninvasive model to monitor the growth of these lesions and the associated angiogenesis in vivo. First, we generated luciferase-expressing transgenic mice by inserting the human ubiquitin C promoter coupled to the firefly luciferase reporter. Injection of luciferin in these mice causes full-body bioluminescence, which can be detected using a low-light CCD camera. Endometrial tissue from these transgenic mice was surgically implanted into nonluminescent recipients. Bioluminescence of lesions was noninvasively imaged after intravenous or intraperitoneal injection of luciferin. Transabdominal luminescence compared well with the location of the transgenic endometriotic lesions, and lesion size correlated with the intensity of luminescence. Systemic treatment with the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset and intensity of the luminescent signal. Caplostatin suppressed the growth of endometriotic lesions by 59% compared with controls. This novel, noninvasive model of endometriosis provides a means to study early angiogenesis in vivo and to monitor endometriotic growth and the efficacy of systemic antiangiogenic therapy. PMID:16723720

  15. Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells.

    PubMed

    Piccinato, Carla A; Neme, Rosa M; Torres, Natália; Sanches, Lívia Renta; Derogis, Priscilla Bento Mattos Cruz; Brudniewski, Heloísa F; Rosa e Silva, Júlio C; Ferriani, Rui A

    2016-04-01

    Endometriosis is an estrogen-dependent disease that afflicts about 10% of women in their reproductive age, causing severe pain and infertility. The potential roles of female steroid hormones in modulating key estrogen-metabolizing enzymes, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), were investigated. The expression of STS and SULT1E1 mRNA in biopsy samples (n=78) of superficial and deep endometriotic lesions, eutopic endometrium of women with endometriosis and endometrium from control patients were compared according to the menstrual cycle phase. Increased STS gene expression was detected in superficial and deep-infiltrating lesions and a reduced SULT1E1 expression was also observed in the eutopic endometrium relative to the superficial lesions. Additionally, a significantly positive correlation was detected between STS and SULT1E1 mRNA expression levels in biopsy specimens collected from the endometriosis patients, and not in control individuals. The actions of female steroid hormones on SULT1E1 and STS expression were evidenced in endometriosis, revealed by increased expression levels in the luteal phase of the cycle. There was an increased STS expression in primary eutopic and ectopic endometrial stromal cells treated with estradiol and progesterone (representative of the luteal phase, n=3). Although an increased STS mRNA expression was observed in hormone-induced endometrial stromal cells in vitro, no difference could be detected between the hormone treatment groups in estradiol formation from estradiol sulfate measured by LC-MS-MS. Interestingly, a greater expression of STS was observed in stromal cells from eutopic endometrium with an agreement in estradiol formation originated from estradiol sulfate. The differential regulation of STS and SULT1E1 could provide insights for novel studies of the therapeutic use of STS inhibitors.

  16. Molecular biology of endometriosis: from aromatase to genomic abnormalities.

    PubMed

    Bulun, Serdar E; Monsivais, Diana; Kakinuma, Toshiyuki; Furukawa, Yuichi; Bernardi, Lia; Pavone, Mary Ellen; Dyson, Matthew

    2015-05-01

    Endometriosis has been initially described as the presence of ectopic endometrial tissue on pelvic organs or in extrapelvic sites; and this has been used as its key pathologic feature ever since. Endometriosis responds to fluctuations in estrogen and progesterone by growth and inflammation, leading to pain aggravated by menses. It was proposed that pelvic endometriosis primarily originate from retrograde menstruation of a critical number of eutopic endometrial cells with stem characteristics. This postulate is supported by the molecular defects found in ectopic endometriotic tissue. Genome-wide differences in CpG methylation between eutopic endometrial and endometriotic stromal cells are present. Defective CpG methylation affecting several genes that encode key transcription factors such as GATA6, steroidogenic factor-1, and estrogen receptor-β in endometriosis gives rise to overproduction of local estrogen and prostaglandins and suppression of progesterone receptor. Progesterone receptor deficiency leads to progesterone resistance, resulting in decreased retinol uptake and retinoic acid production and altered retinoic acid action. These molecular defects collectively give rise to poor cellular differentiation, enhanced survival, and increased inflammation, which are the biological hallmarks of endometriotic tissue.

  17. Case study of a rare form of endometriosis

    PubMed Central

    Cirstoiu, M; Bodean, O; Secara, D; Munteanu, O; Cirstoiu, C

    2013-01-01

    Endometriosis is a common, benign, chronic, estrogen-dependent disorder. The endometrial tissue implants itself outside the uterus and can be usually found in the pelvis or, in rare cases, it can be found nearly anywhere in the body. There are no pathognomonic symptoms of this disease, therefore, in some cases the tumors are incidentally discovered during surgery. Deep infiltrative endometriosis (DIE) is a rare form of this condition, which mostly affects the uterosacral ligaments, the rectovaginal space, and the upper third of the posterior vaginal wall, the bowel, and the urinary tract. We present the case of a 29-year-old pregnant female who was diagnosed with infiltrative endometriosis during the cesarean section at 38 weeks of gestation. The tumors involving the vesicouterine peritoneum had a tendency of infiltrating the urinary bladder, but the patient had been completely asymptomatic prior to this incidental discovery. As cited by literature, the discovery and management of urinary endometriosis, as well as that of other localizations of DIE, is not based on high-level evidence data, but rather on case-series reported by surgical teams working in different centers worldwide. PMID:23599823

  18. MR imaging in deep pelvic endometriosis: a pictorial essay.

    PubMed

    Coutinho, Antônio; Bittencourt, Leonardo Kayat; Pires, Cíntia E; Junqueira, Flávia; Lima, Cláudio Márcio Amaral de Oliveira; Coutinho, Elisa; Domingues, Marisa A; Domingues, Romeu C; Marchiori, Edson

    2011-01-01

    Deep pelvic endometriosis is an important gynecologic disorder that is responsible for severe pelvic pain and is defined as subperitoneal invasion that exceeds 5 mm in depth. Deep pelvic endometriosis can affect the retrocervical region, uterosacral ligaments, rectum, rectovaginal septum, vagina, urinary tract, and other extraperitoneal pelvic sites. It is commonly associated with dysmenorrhea, dyspareunia, pelvic pain, urinary tract symptoms, and infertility. Because surgery remains the best therapeutic option for affected patients, the accurate preoperative assessment of the extension of endometriotic disease is extremely important. Pelvic magnetic resonance (MR) imaging is a noninvasive method with high spatial resolution that allows multiplanar evaluation of deep pelvic endometriosis and good tissue characterization, but without the use of ionizing radiation or iodinated contrast agents. MR imaging yields important findings that help grade the disease and identify subperitoneal lesion extension and other associated disease entities, thereby facilitating accurate diagnosis and adequate treatment. Radiologists should be familiar with the MR imaging findings of deep infiltrating endometriosis in various anatomic locations so that they can provide information that allows adequate presurgical counseling.

  19. Diagnostic Accuracy of Urinary Cytokeratin 19 Fragment for Endometriosis

    PubMed Central

    Savaris, R. F.; Ali, S.; Brophy, S.; Tomazic-Allen, S.; Chwalisz, K.

    2015-01-01

    Endometriosis affects up to 10% of women of reproductive age and 176 million women worldwide. The prevalence in women with infertility is between 30% and 50% but may be higher in women with pelvic pain, interstitial cystitis, or irritable bowel syndrome. Cytokeratin 19 has been suggested as a potential biomarker in urine for the diagnosis of this condition. The objective of this study was to prospectively determine the accuracy and the performance of a urinary cytokeratin 19 (uCYFRA 21-1) test for diagnosing endometriosis. Ninety-eight consecutive women who underwent laparoscopy had a urinary sample obtained before surgery and were included in the study. Endometriosis was diagnosed by laparoscopy and pathology in 64.3% (63 of 98 women). The estimates and 95% confidence intervals for sensitivity, specificity, positive and negative predictive values, and likelihood ratios were 11.1% (4.5%-21.5%), 94.3% (80.8%-99.3%), 77.7% (39.9-97.1), 37% (27-47.9), 1.94 (0.43-8.86), and 0.94 (0.84-1.06), respectively. Despite the high specificity, the uCYFRA 21-1 test has limited value for clinical practice to discriminate between women with and without endometriosis. PMID:25296695

  20. [Gestrinone in pelvic endometriosis. A one-year evaluation].

    PubMed

    Cervantes Villarreal, E; García Zamarripa, H R; Herrera Prado, E; Barrón Vallejo, J

    1995-08-01

    The therapeutical effectiveness of gestrinone in endometriosis treatment, as well as its long term side effects, were evaluated. Prospective, clinical trial. At "Dr. Alejandro Castanedo Kimball" Hospital (PEMEX). Salamanca, Guanajuato. México. Thirty women with laparoscopically confirmed endometriosis, were studied. Subjects received 2.5 mg. of gestrinone two times per week for 6 months. Laparoscopy was performed before treatment, and clinical response was determined by second laparoscopy after 6 months. The pregnancy rate, frequency of side effects and recurrence of symptoms were determined. Median total endometriosis scores and symptoms decreased significantly after treatment. Four pregnancies were observed after treatment. The principal side effects were: ponderal increase, changes in the voice and hirsutism. However, the side effects disappeared after one year of clinical survey. The results indicate that gestrinone is effective in the treatment of pelvic endometriosis. In despite of a clear benefic effect on stage of the disease and symptoms; the use of gestrinone should weigh the risk-benefit (cost versus metabolic side effects) of treatment.

  1. Correlation of histological and macroscopic findings in peritoneal endometriosis

    PubMed Central

    Strehl, Johanna D; Hackl, Janina; Wachter, David L; Klingsiek, Peter; Burghaus, Stefanie; Renner, Stefan P; Fasching, Peter A; Hartmann, Arndt; Beckmann, Matthias W

    2014-01-01

    Context: In the last two decades, a color based concept of disease activity in peritoneal endometriosis has been in use in the clinical context, with red lesions being considered active and black or white lesions being interpreted as less active or dormant. Objective: Our aim was to analyze 4 main color categories of peritoneal endometriosis (black, white, red and brown) in one single patient group using histomorphological and immunohistochemical methods. Design: 65 endometriosis lesions (30 black, 17 white, 11 brown, 7 red) were resected from 47 premenopausal, nulliparous women which had not received exogenous hormones for at least six months prior to the operation. Specimen workup, histomorphological analysis and immunohistochemical analysis were performed in a standardized manner. Results: The color categories showed a broad overlap in proliferative activity and hormone receptor expression. Differences were found in lesion morphology. Adjacent stromal reaction in particular showed a marked increase from red through brown and black to white lesions. Differences were also seen in gland pattern and gland content. Conclusions: Lesion colors in peritoneal endometriosis seem to be determined by gland content and a varying adjacent stromal reaction and more likely reflect an aging process than different levels of disease activity. PMID:24427335

  2. ENVIRONMENTAL PCB AND PESTICIDE EXPOSURE AND RISK OF ENDOMETRIOSIS

    EPA Science Inventory

    Environmental PCB and Pesticide Exposure and Risk of Endometriosis

    Germaine M. Buck1, John M. Weiner2, Hebe Greizerstein3, Brian Whitcomb1, Enrique Schisterman1, Paul Kostyniak3, Danelle Lobdell4, Kent Crickard5, and Ralph Sperrazza5

    1Epidemiology Branch, Division o...

  3. Co-micronized Palmitoylethanolamide/Polydatin Treatment Causes Endometriotic Lesion Regression in a Rodent Model of Surgically Induced Endometriosis

    PubMed Central

    Di Paola, Rosanna; Fusco, Roberta; Gugliandolo, Enrico; Crupi, Rosalia; Evangelista, Maurizio; Granese, Roberta; Cuzzocrea, Salvatore

    2016-01-01

    Endometriosis is a chronic, painful disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. Palmitoylethanolamide (PEA), an endogenous fatty acid amide, has anti-inflammatory and neuroprotective effects. PEA lacks free radical scavenging activity, unlike polydatin (PLD), a natural precursor of resveratrol. The aim of this study was to investigate the effect of orally administered co-micronized PEA/polydatin [m(PEA/PLD)] in an autologous rat model of surgically induced endometriosis. Endometriosis was induced in female Wistar albino rats by auto-transplantation of uterine squares (implants) into the intestinal mesentery and peritoneal cavity. Rats were distributed into one control group and one treatment group (10 animals each): m(PEA/PLD) 10 mg/kg/day. At 28 days after surgery the relative volume of the endometrioma was determined. Endometrial-like tissue was confirmed by histology: Masson trichrome and toluidine blue were used to detect fibrosis and mast cells, respectively. The treated group displayed a smaller cyst diameter, with improved fibrosis score and mast cell number decrease. m(PEA/PLD) administration decreased angiogenesis (vascular endothelial growth factor), nerve growth factor, intercellular adhesion molecule, matrix metalloproteinase 9 expression, and lymphocyte accumulation. m(PEA/PLD) treatment also reduced peroxynitrite formation, (poly-ADP)ribose polymerase activation, IkBα phosphorylation and nuclear facor-kB traslocation in the nucleus. Our results suggested that m(PEA/PLD) may be of use to inhibit development of endometriotic lesions in rats. PMID:27790149

  4. Co-micronized Palmitoylethanolamide/Polydatin Treatment Causes Endometriotic Lesion Regression in a Rodent Model of Surgically Induced Endometriosis.

    PubMed

    Di Paola, Rosanna; Fusco, Roberta; Gugliandolo, Enrico; Crupi, Rosalia; Evangelista, Maurizio; Granese, Roberta; Cuzzocrea, Salvatore

    2016-01-01

    Endometriosis is a chronic, painful disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. Palmitoylethanolamide (PEA), an endogenous fatty acid amide, has anti-inflammatory and neuroprotective effects. PEA lacks free radical scavenging activity, unlike polydatin (PLD), a natural precursor of resveratrol. The aim of this study was to investigate the effect of orally administered co-micronized PEA/polydatin [m(PEA/PLD)] in an autologous rat model of surgically induced endometriosis. Endometriosis was induced in female Wistar albino rats by auto-transplantation of uterine squares (implants) into the intestinal mesentery and peritoneal cavity. Rats were distributed into one control group and one treatment group (10 animals each): m(PEA/PLD) 10 mg/kg/day. At 28 days after surgery the relative volume of the endometrioma was determined. Endometrial-like tissue was confirmed by histology: Masson trichrome and toluidine blue were used to detect fibrosis and mast cells, respectively. The treated group displayed a smaller cyst diameter, with improved fibrosis score and mast cell number decrease. m(PEA/PLD) administration decreased angiogenesis (vascular endothelial growth factor), nerve growth factor, intercellular adhesion molecule, matrix metalloproteinase 9 expression, and lymphocyte accumulation. m(PEA/PLD) treatment also reduced peroxynitrite formation, (poly-ADP)ribose polymerase activation, IkBα phosphorylation and nuclear facor-kB traslocation in the nucleus. Our results suggested that m(PEA/PLD) may be of use to inhibit development of endometriotic lesions in rats.

  5. EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis.

    PubMed

    Greaves, Erin; Horne, Andrew W; Jerina, Helen; Mikolajczak, Marta; Hilferty, Lisa; Mitchell, Rory; Fleetwood-Walker, Sue M; Saunders, Philippa T K

    2017-03-10

    Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.

  6. EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis

    PubMed Central

    Greaves, Erin; Horne, Andrew W.; Jerina, Helen; Mikolajczak, Marta; Hilferty, Lisa; Mitchell, Rory; Fleetwood-Walker, Sue M.; Saunders, Philippa T. K.

    2017-01-01

    Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis. PMID:28281561

  7. Circulating microRNAs as diagnostic biomarkers for endometriosis: privation and promise

    PubMed Central

    Nothnick, Warren B.; Al-Hendy, Ayman; Lue, John R.

    2015-01-01

    Endometriosis represents a major medical concern in women of reproductive age. One of the major hurdles in successful treatment of endometriosis that remains is the limitation in the process of timely disease diagnosis. A simple blood test for endometriosis-specific biomarkers would offer a timelier, accurate diagnosis for the disease allowing earlier treatment intervention. While there have been considerable efforts to identify such biomarkers, no clear choice for such non-invasive diagnostic tools have been identified. MicroRNAs are small non-coding RNAs which have been intensively evaluated as biomarkers for several diseases and may hold promise for endometriosis diagnosis. In this review, we highlight the need for non-invasive testing for endometriosis, discuss the potential use of miRNAs as diagnostic tools for this disease, and consider potential limitations in the use of these small RNA molecules as diagnostic markers for endometriosis. PMID:25757811

  8. Catamenial pneumothorax due to solitary localization of diaphragmatic endometriosis

    PubMed Central

    Elia, Stefano; De Felice, Laura; Varvaras, Dimitrios; Sorrenti, Giuseppe; Mauriello, Alessandro; Petrella, Giuseppe

    2015-01-01

    Introduction Catamenial pneumothorax (CP) is a spontaneous recurrent pneumothorax occurring in women in reproductive age. The etiology of CP has been associated with thoracic endometriosis and is its most common presentation. Presentation of case A case of right catamenial pneumothorax in a 38 year old woman is presented in which three episodes of CP occurred within 72 h of menses in a 6 month period. The patient underwent videothoracoscopy that revealed a solitary localization of diaphragmatic endometriosis. After surgical pleurodesis and based on final pathology of resected lesion, hormonal treatment was started. The outcome was uneventful and the patients is symptom-free at 6 months. Discussion Catamenial pneumothorax (CP) is a rare clinical entity characterized by lung collapse during menstruation, believed to be secondary to pleural endometriosis. Nearly all catamenial pneumothorax occur on the right side as pleural lesions are almost exclusively right-sided. Diagnostic imaging is based on high resolution computed tomography (HRCT) and, preferably, magnetic resonance imaging (MRI) since it is able to detect the blood products in the endometrial deposits. However the lack of macroscopic findings at surgery makes this condition still under-diagnosed. Based on the solitary diaphragmatic localization of endometriosis in our case we preferred to limit surgery to videothoracoscopic pleurodesis and start hormonal treatment with successful outcome. Conclusion Catamenial pneumothorax is the most common presentation of thoracic endometriosis syndrome and should always be suspected in women in childbearing age. Treatment option are still debated but best results are achieved by videothoracoscopic pleurodesis combined with hormonal therapy. PMID:25981153

  9. Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

    PubMed

    Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

    2014-05-01

    To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

  10. Actinomyces and Related Organisms in Human Infections

    PubMed Central

    Wade, William G.

    2015-01-01

    SUMMARY Actinomyces israelii has long been recognized as a causative agent of actinomycosis. During the past 3 decades, a large number of novel Actinomyces species have been described. Their detection and identification in clinical microbiology laboratories and recognition as pathogens in clinical settings can be challenging. With the introduction of advanced molecular methods, knowledge about their clinical relevance is gradually increasing, and the spectrum of diseases associated with Actinomyces and Actinomyces-like organisms is widening accordingly; for example, Actinomyces meyeri, Actinomyces neuii, and Actinomyces turicensis as well as Actinotignum (formerly Actinobaculum) schaalii are emerging as important causes of specific infections at various body sites. In the present review, we have gathered this information to provide a comprehensive and microbiologically consistent overview of the significance of Actinomyces and some closely related taxa in human infections. PMID:25788515

  11. Obstetrical Complications in Women with Endometriosis: A Cohort Study in Japan

    PubMed Central

    Harada, Takashi; Taniguchi, Fuminori; Onishi, Kazunari; Kurozawa, Youichi; Hayashi, Kunihiko; Harada, Tasuku

    2016-01-01

    Background Endometriosis, which occurs in approximately 10% of women of reproductive age, is defined as the presence of endometrial tissue outside the uterus. Women with endometriosis are more likely to have difficulty conceiving and tend to receive infertility treatment, including assisted reproductive technology (ART) therapy. There has not yet been a prospective cohort study examining the effects of endometriosis on pregnancy outcome in pregnant Japanese women. Methodology This was a prospective cohort study of the incidence of obstetrical complications in women with endometriosis using data of the Japan Environment & Children’s Study (JECS). Included in this study were 9,186 pregnant women in the JECS with or without a history of endometriosis who gave birth or stillbirth or whose pregnancy was terminated with abortion between February and December 2011. Main Outcome Measures The effects of endometriosis on pregnancy outcome. Results Of the 9,186 pregnant women in the JECS, 4,119 (44.8%) had obstetrical complications; 330 participants reported a diagnosis of endometriosis before pregnancy, and these women were at higher risk for complications of pregnancy than those without a history of endometriosis (odds ratio (OR) = 1.50; 95% confidence interval (CI) 1.20 to 1.87). Logistic regression analyses showed that the adjusted OR for obstetrical complications of pregnant women who conceived naturally and had a history of endometriosis was 1.45 (CI 1.11 to 1.90). Among pregnant women with endometriosis, the ORs of preterm premature rupture of the membranes (PROM) and placenta previa were significantly higher compared with women never diagnosed with endometriosis who conceived naturally or conceived after infertility treatment, except for ART therapy (OR 2.14, CI 1.03–4.45 and OR 3.37, CI 1.32–8.65). Conclusions This study showed that endometriosis significantly increased the incidence of preterm PROM and placenta previa after adjusting for confounding of the

  12. Evaluation of biodegradable microspheres containing nomegestrol acetate in a rat model of endometriosis.

    PubMed

    Zhang, Jianfeng; Zhu, Yan; Zhou, Xianying; Hao, Shufang; Xie, Shuwu; Zhou, Jieyun; Guo, Xiangjie; Li, Zhao; Huang, Yunsheng; Chen, Qinghua

    2014-12-18

    We assessed the efficacy of biodegradable microspheres (MSs) containing nomegestrol acetate (NOMAC) for treatment of endometriosis in a rat model and investigated its preliminary mechanism of action. Sprague-Dawley rats with surgically implanted endometrial autografts were divided randomly into four groups of thirteen rats each, and subcutaneously injected twice (10d apart) with either empty MSs or MSs containing nomegestrol acetate (NOMAC-MS; 27-800mg per kg of rat body weight). Twenty-one days after the first injection, blood and endometriotic tissues were collected and assayed for changes in endometriotic tissue, serum hormone, liver function parameters, and apoptotic protein. No remarkable irritation was observed at the site of injection. NOMAC-MS treatment significantly reduced the volume of the endometrial autografts, decreased serum levels of estradiol, progesterone, triiodothyronine, and alanine aminotransferase, and decreased levels of estrogen receptor alpha protein. Furthermore, NOMAC-MS at the highest dose significantly reduced serum aspartate aminotransferase and endometrial antibody, reduced the Bcl-2/Bax protein ratio, and increased caspase-3 and caspase-9 proteins. There was no pronounced difference observed in alkaline phosphatase, carbohydrate antigen 125, progesterone receptor, or vascular endometrial growth factor receptor 2 (VEGFR2) in any of the tested groups relative to the control. NOMAC-MS significantly changed the expression of apoptotic protein only at the highest dose. Our findings warrant the further investigation of sustained application of steroid hormone via microspheres for the treatment of endometriosis.

  13. Photodynamic therapy (PDT) of endometrium primary cultures serving as an in-vitro model for endometriosis

    NASA Astrophysics Data System (ADS)

    Herter, Wiebke; Viereck, Volker; Keckstein, J.; Steiner, Rudolf W.; Rueck, Angelika C.

    1994-05-01

    As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.

  14. Photodynamic treatment (PDT) of endometrium primary cultures serving as an in-vitro-model for endometriosis

    NASA Astrophysics Data System (ADS)

    Werter, Wiebke; Viereck, Volker; Keckstein, J.; Steiner, Rudolf W.; Rueck, Angelika C.

    1994-05-01

    As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.

  15. Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation

    PubMed Central

    Sanghera, Sabina; Barton, Pelham; Bhattacharya, Siladitya; Horne, Andrew W; Roberts, Tracy Elizabeth

    2016-01-01

    Objective Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and ‘no treatment’ to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. Methods We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. Results On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. Conclusions There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis. PMID:27084280

  16. Evaluation of Efficacy and Safety of Dan'e-Fukang Soft Extract in the Treatment of Endometriosis: A Meta-Analysis of 39 Randomized Controlled Trials Enrolling 5442 Patients

    PubMed Central

    Li, Yantao; Li, Te

    2017-01-01

    Objective. To systematically evaluate the efficacy and safety of Dan'e-fukang soft extract in endometriosis treatment. Method. PubMed, CNKI, Wanfang Database, VIP, SinoMed, and Cochrane Library were searched. Randomized controlled trials (RCTs) comparing the efficacy of Dan'e-fukang soft extract and conventional western medicines for endometriosis treatment were included. The data were extracted independently by two people and analyzed using RevMan 5.2.0 software. The relative risk (RR) and mean difference (MD) with 95% confidence intervals were considered as effective outcome indicators. Results. Thirty-nine papers including 5442 patients with endometriosis were included in this study. A meta-analysis revealed that Dan'e-fukang soft extract was more efficient than gestrinone in the treatment of endometriosis (RR = 1.08, 95% CI = 1.03 to 1.15, I2 = 71%, REM, 18 trials) and its efficacy was comparable to that of danazol and mifepristone. Dan'e-fukang soft extract was also as effective as gestrinone and mifepristone in terms of relapse rate and relieving dysmenorrhea. The incidence of adverse reactions was lower than that of conventional western medicines. Conclusions. The results of this study showed that Dan'e-fukang soft extract offers certain advantages in endometriosis treatment, but rigorously designed, strictly implemented RCTs are needed to further validate its efficacy. PMID:28337228

  17. Umbilical Nodule with Cyclical Bleeding: A Case Report and Literature Review of Atypical Endometriosis

    PubMed Central

    de Freitas, Cláudia V. Marques; Câmara, Sara Filipa Camacho; Vieira, José Joaquim Nunes

    2016-01-01

    Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. It affects 3 to 10 percent of women of reproductive age. Umbilical endometriosis is rare, with an estimated incidence of 0.5–1.0% among all cases of endometriosis, and is usually secondary to prior laparoscopic surgery involving the umbilicus. In this report, we described a case of umbilical endometriosis treated with surgical resection and highlight the great importance of medical history compared to complementary diagnostic tests that can be sometimes inconclusive. PMID:27747115

  18. Study of experimental endometriosis using fluorescence of eosin-tamoxifen association

    NASA Astrophysics Data System (ADS)

    Brogniez, A.; Mordon, Serge R.; Devoisselle, Jean-Marie; Querleu, Denis; Brunetaud, Jean Marc

    1993-08-01

    The main problem of endometriosis is the detection of microscopic and atypical lesions. The successful destruction of these endometriotic sites depends on their detection. This study aimed to develop a spectrofluorometric method to increase the sensitivity of detection of endometriosis. A surgical-induced endometriosis was performed in ten rabbits. Five weeks later, the fluorescence of these endometriotic lesions was studied after injection of tamoxifen and local application of eosin. This fluorescence was compared with that of healthy broad ligament and that obtained without tamoxifen and without eosin. A spectral analysis showed a specific fluorescence of eosin-tamoxifen association, more intense than autofluorescence and selectively observed within endometriosis.

  19. Newer synthetic progestins for the treatment of endometriosis.

    PubMed

    Kistner, R W

    1970-01-01

    This paper outlines methods of therapy utilizing newer combinations of estrogens and progestins. The specific agent and length of treatment depends on the extent of disease, severity of symptoms, presence of infertility and response to pseudopregnancy. Structural formulas for 19 synthetic preparations are shown. Of 36 patients with proven endometriosis in which pseudopregnancy was induced by the use of these newer agents, satisfactory objective in 82%. Pregnancy occurred later in 6 of 10 patients who had previously been infertile and wished to become pregnant. The optimum maintenance dose is 4-6 mg of chlormadinone acetate or ethnodiol diacetate with .2 mg of mestranol and 5-10 mg of megestrol acetate with .2 mg of ethniyl estradiol. Dosage is increased only when break through bleeding occurs. Gain in weight occurred in almost 1/2 of the patients. The decidual reaction was just as great as that produced formerly by large doses of Enovid. In a more recent study 60 patients were treated with Norlestrin, 20 with Lyndiol and 20 with Ovral. Satisfactory objective and subjective remissions were obtained in 89%. Pregnancy has occurred subsequently in 17 to 43 patients who desired pregnancy. All infants have been normal. The optimum maintenance doses seem to be 10-15 mg if Norlestrin, 2.5-5 mg Lyndiol or .5-1 mg of Ovral. The most common side effect was weight gain in 35%. These agents may be used prior to conservative surgery in order to soften areas of fibrotic endometriosis or to pinpoint areas otherwise overlooked. The length of preoperative treatment depends on the extent of disease, 6 weeks being usual. The indication for prolonged pseudopregnancy is recurrent endometriosis following surgery, also proven vaginal endometriosis. Subsequent to conservative surgery, 12 to 24 weeks of therapy are given in order to inhibit ovulation and prevent reactivation of any remaining areas of endometriosis. Tables show commercial combinations and dosage regimens. Nausea, break

  20. Human papillomavirus-related esophageal cancer survival

    PubMed Central

    Guo, Lanwei; Liu, Shuzheng; Zhang, Shaokai; Chen, Qiong; Zhang, Meng; Quan, Peiliang; Sun, Xi-Bin

    2016-01-01

    Abstract Background: Human papillomavirus (HPV) has been identified to be related to progression of esophageal cancer. However, the results remain controversial. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Methods: The electronic databases of MEDLINE and Excerpta Medica database were searched till April 30, 2016. Study-specific risk estimates were pooled using a random-effects model. Results: Ten studies involving a total of 1184 esophageal cancer cases were included in this meta-analysis. The pooled hazard ratio comparing HPV-positive to HPV-negative esophageal cancers was 1.03 (95% confidence interval 0.78–1.37), which was not significantly correlated with improved survival. However, HPV-16-positive patients might have a significantly favorable survival (hazard ratio 0.73, 95% confidence interval 0.44–1.21). Conclusion: The meta-analysis indicated that HPV infection may not be of prognostic utility in the evaluation of factors contributing to esophageal cancer. Further large prospective studies are encouraged to stratify survival analysis by HPV type. PMID:27861358

  1. Enhanced Endometriosis Archiving Software (ENEAS): An Application for Storing, Retrieving, Comparing, and Sharing Data of Patients Affected by Endometriosis Integrated in the Daily Practice.

    PubMed

    Centini, Gabriele; Zannoni, Letizia; Lazzeri, Lucia; Buiarelli, Paolo; Limatola, Gianluca; Petraglia, Felice; Seracchioli, Renato; Zupi, Errico

    Endometriosis is a chronic benign disease affecting women of fertile age, associated with pelvic pain and subfertility, often with negative impacts on quality of life. Meetings involving 5 gynecologists skilled in endometriosis management and 2 informatics technology consultants competent in data management and website administration were enlisted to create an endometriosis databank known as ENEAS (Enhanced Endometriosis Archiving Software). This processing system allows users to store, retrieve, compare, and correlate all data collected in conjunction with different Italian endometriosis centers, with the collective objective of obtaining homogeneous data for a large population sample. ENEAS is a web-oriented application that can be based on any open-source database that can be installed locally on a server, allowing collection of data on approximately 700 items, providing standardized and homogeneous data for comparison and analysis. ENEAS is capable of generating a sheet incorporating all data on the management of endometriosis that is both accurate and suitable for each individual patient. ENEAS is an effective and universal web application that encourages providers in the field of endometriosis to use a common language and share data to standardize medical and surgical treatment, with the main benefits being improved patient satisfaction and quality of life.

  2. Hormonal therapy for endometriosis: from molecular research to bedside.

    PubMed

    Tosti, Claudia; Biscione, Antonella; Morgante, Giuseppe; Bifulco, Giuseppe; Luisi, Stefano; Petraglia, Felice

    2017-02-01

    Endometriotic lesions are associated with hormonal imbalance, including increased estrogen synthesis, metabolism and progesterone resistance. These hormonal changes cause increased proliferation, inflammation, pain and infertility. Hormonal imbalances are targets for treatment. Therapeutic strategies and innovations of hormonal drugs for endometriosis are increasing. Acting on estrogen receptors are hormonal drugs decreasing systemic and local estrogen synthesis (GnRH analogs, GnRH antagonists, Aromatase inhibitors) or estrogen activity (selective estrogen receptor modulators). The progesterone resistance is counteracted by progestins (Medroxyprogesterone acetate, Dienogest, Danazol, Levonorgestrel) or by Selective progesterone receptor modulators, a class of drugs under development. The future trend will be to define new drugs to use for prolonged period of time and with poor side effects considering endometriosis a chronic disease.

  3. Negotiating science and experience in medical knowledge: gynaecologists on endometriosis.

    PubMed

    Whelan, Emma

    2009-04-01

    This paper analyses the gynaecological literature on endometriosis, particularly endometriosis classification, to evaluate the epistemological concepts it uses. A qualitative content analysis was conducted on a sample of gynaecological literature published between 1985 and 2000, a period that witnessed the explosion of both evidence-based and patient-centred models of medicine, with their dwelling emphases on science and experience. It was found that the discourse of science is used strategically in this literature as a formal epistemology to lend weight to authors' claims and to guide medical thinking and research. However, gynaecologists also use the notion of experience to assert their own credibility and to question the credibility of other experts. In fact, accounts of their own experience and the experiential accounts of their patients are foundational to gynaecologists' claims-making activities, including their engagement with scientific research.

  4. [Establishment of endometriosis subcutaneous model in immunodeficient nude mice].

    PubMed

    Ni, H J; Zhang, Z; Dai, Y D; Zhang, S Y

    2016-09-06

    Objective: To establish a model of endometriosis in immunodeficient nude mice and compare the outcome of the model construction between two different techniques. Methods: Eighteen nude mice were divided into 2 groups, with 9 mice in each group. All nude mice received a subcutaneous transplantation of endometrial fragments, followed by sutured the wounded skin (sutured group) or not (no-sutured group). Then the success rate of the model construction, inflammation of the wounds and the animal survival rate in the two groups were analyzed. Result: In no-sutured group, the survival rate of animal and the success rate of the model construction were 9/9 and 8/9 respectively, with 8/9 survival rate and 7/9 success rate in sutured group. No significant difference was found between the two groups. And no obvious inflammation was presented in the wounds for both groups. Conclusion: It is an effective method to establish animal model of endometriosis by subcutaneous transplantation in nude mice. After transplantation, it does not affect the outcome of the survival rate of the animal and the success rate of the model construction whether we suture the wounded skin. Considering the shorter operation time, we found it's a simpler and time saving method to establish endometriosis by subcutaneously transplanting endometrial fragments in nude mice with no skin-sutured. And this model is worth of promotion.

  5. Molecular aspects of development and regulation of endometriosis

    PubMed Central

    2014-01-01

    Endometriosis is a common and painful condition affecting women of reproductive age. While the underlying pathophysiology is still largely unknown, much advancement has been made in understanding the progression of the disease. In recent years, a great deal of research has focused on non-invasive diagnostic tools, such as biomarkers, as well as identification of potential therapeutic targets. In this article, we will review the etiology and cellular mechanisms associated with endometriosis as well as the current diagnostic tools and therapies. We will then discuss the more recent genomic and proteomic studies and how these data may guide development of novel diagnostics and therapeutics. The current diagnostic tools are invasive and current therapies primarily treat the symptoms of endometriosis. Optimally, the advancement of “-omic” data will facilitate the development of non-invasive diagnostic biomarkers as well as therapeutics that target the pathophysiology of the disease and halt, or even reverse, progression. However, the amount of data generated by these types of studies is vast and bioinformatics analysis, such as we present here, will be critical to identification of appropriate targets for further study. PMID:24927773

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

    PubMed

    Christensen, B; Schindler, A E

    1996-09-01

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

  7. Pelvic pain after gonadotropin administration as a potential sign of endometriosis.

    PubMed

    Jun, Sunny Hee; Lathi, Ruth B

    2007-10-01

    We describe five patients who developed significant pelvic pain, requiring narcotics, during a controlled ovarian hyperstimulation cycle and who were surgically diagnosed with significant endometriosis. Severe pain, especially if it requires narcotics, is unusual for patients undergoing controlled ovarian hyperstimulation and may be an indicator of endometriosis.

  8. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications

    PubMed Central

    Stratton, Pamela; Berkley, Karen J.

    2011-01-01

    BACKGROUND Many clinicians and patients believe that endometriosis-associated pain is due to the lesions. Yet causality remains an enigma, because pain symptoms attributed to endometriosis occur in women without endometriosis and because pain symptoms and severity correlate poorly with lesion characteristics. Most research and reviews focus on the lesions, not the pain. This review starts with the recognition that the experience of pain is determined by the central nervous system (CNS) and focuses on the pain symptoms. METHODS Comprehensive searches of Pubmed, Medline and Embase were conducted for current basic and clinical research on chronic pelvic pain and endometriosis. The information was mutually interpreted by a basic scientist and a clinical researcher, both in the field of endometriosis. The goal was to develop new ways to conceptualize how endometriosis contributes to pain symptoms in the context of current treatments and the reproductive tract. RESULTS Endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the CNS. This engagement provides a mechanism by which the dynamic and hormonally responsive nervous system is brought directly into play to produce a variety of individual differences in pain that can, in some women, become independent of the disease itself. CONCLUSIONS Major advances in improving understanding and alleviating pain in endometriosis will likely occur if the focus changes from lesions to pain. In turn, how endometriosis affects the CNS would be best examined in the context of mechanisms underlying other chronic pain conditions. PMID:21106492

  9. Effect of Helixor A on Natural Killer Cell Activity in Endometriosis

    PubMed Central

    Jeung, In-Cheul; Chung, Youn-Jee; Chae, Boah; Kang, So-Yeon; Song, Jae-Yen; Jo, Hyun-Hee; Lew, Young-Ok; Kim, Jang-Heub; Kim, Mee-Ran

    2015-01-01

    Background and Aim: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosis Materials and Methods: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker. Results: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p = 0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p = 0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p = 0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p = 0.014) in stage III/IV. Conclusions: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results

  10. Endometriosis Under Estradiol Stimulation Imaged Using 18F-FDG and Its Control After Estradiol Cessation and Progesterone Hormonal Replacement.

    PubMed

    Arsenault, Frédéric; Turcotte, Éric

    2016-03-01

    Endometriosis is a frequent and benign cause of disabling abdominal pain, for which a diagnosis suspicion is clinically raised, but its confirmation necessitates a surgical exploration by laparoscopy. Foci of endometriosis proliferate under estrogen stimulation, like normal endometrium. We present a patient under estradiol stimulation for a history of endometrial cancer who underwent a PET/CT scan to assess an abdominal lesion showing a high F-FDG uptake, which normalized under progesterone hormonal replacement and cessation of estradiol. Two consecutive biopsies confirmed endometriosis. F-FDG evaluation of endometriosis under estrogen stimulation could be a promising approach to refractory endometriosis assessment.

  11. Embryo quality before and after surgical treatment of endometriosis in infertile patients

    PubMed Central

    Burney, Richard O.; Behr, Barry; Milki, Amin A.; Westphal, Lynn M.; Lathi, Ruth B.

    2009-01-01

    Purpose To investigate the hypothesis that surgical treatment of endometriosis in infertile patients may improve pregnancy rates by improving embryo quality. Methods We conducted a retrospective evaluation of 30 infertile patients treated with in vitro fertilization (IVF) before and after surgery for endometriosis. Patients served as their own controls and only cycles with similar stimulation protocols were compared. Results Using standard visual evaluation, embryo quality on day 3 was similar before and after surgical treatment of endometriosis. Fifty seven percent of patients had stage I–II endometriosis and 43% had stage III–IV disease. No patients had a live birth after the first IVF cycle and 43% of patients had a live birth with the IVF cycle after surgery. Conclusions Surgical treatment of endometriosis does not alter embryo quality in patients with infertility treated with IVF. PMID:19214735

  12. Video-assisted laparoscopy for the detection and diagnosis of endometriosis: safety, reliability, and invasiveness

    PubMed Central

    Schipper, Erica; Nezhat, Camran

    2012-01-01

    Endometriosis is a highly enigmatic disease with multiple presentations ranging from infertility to severe pain, often causing significant morbidity. Video-assisted laparoscopy (VALS) has now replaced laparotomy as the gold standard for the diagnosis and management of endometriosis. While imaging has a role in the evaluation of some patients, histologic examination is needed for a definitive diagnosis. Laboratory evaluation currently has a minor role in the diagnosis of endometriosis, although studies are underway investigating serum markers, genetic studies, and endometrial sampling. A high index of suspicion is essential to accurately diagnose this complex condition, and a multidisciplinary approach is often indicated. The following review discusses laparoscopic diagnosis of endometriosis from the pre-operative evaluation of patients suspected of having endometriosis to surgical technique for safe and adequate laparoscopic diagnosis of the condition and postsurgical care. PMID:22927769

  13. Endometriosis and type 1 allergies/immediate type hypersensitivity: a systematic review.

    PubMed

    Bungum, Helle Folge; Vestergaard, Christian; Knudsen, Ulla Breth

    2014-08-01

    Endometriosis is a chronic and debilitating disorder affecting up to 5-10% of women in reproductive age. Investigators have described deficiency in cellular immunity in women suffering from endometriosis, and in the recent years endometriosis has been linked to other diseases, allergic disease being one of them. The objective of this paper is to systematically review the existing literature on the possible association between endometriosis and allergic disease. This review is based on the recommendations by the preferred reporting of systematic reviews and meta-analysis (PRISMA) statement. PubMed and Embase were searched for studies on women diagnosed with endometriosis and with manifestations of allergic disease who were compared to a reference group. Out of 316 articles screened, 6 were reviewed and 5 ultimately met the inclusion criteria. Four out of the five studies reported a positive correlation between endometriosis and allergic manifestations, including hay fever, sinus allergic rhinitis, and food intolerance/sensitivities (food allergy). Investigators reported an odds ratio (OR) as high as 4.28 (95% CI: 2.93-6.27) for a positive history of allergy among women suffering from endometriosis. Equivocal results were found on asthma prevalence in women with endometriosis. Due to the heterogeneity of the included studies, no meta-analyses could be performed. The available literature clearly indicates that women with endometriosis are at an increased risk of allergic disorders compared to controls, but due to the lack of a concise definition of allergic disease and therefore diagnostic criteria, further studies are needed in order to draw firm conclusions on the association between endometriosis and allergic disease.

  14. Association of Chronic Pelvic Pain and Endometriosis With Signs of Sensitization and Myofascial Pain

    PubMed Central

    Stratton, Pamela; Khachikyan, Izabella; Sinaii, Ninet; Ortiz, Robin; Shah, Jay

    2014-01-01

    Objective To evaluate sensitization, myofascial trigger points, and quality of life in women with chronic pelvic pain with and without endometriosis. Methods A cross-sectional prospective study of women aged 18 to 50 with pain suggestive of endometriosis and healthy, pain-free volunteers without history of endometriosis. Patients underwent a physiatric neuro-musculoskeletal assessment of clinical signs of sensitization and myofascial trigger points in the abdominopelvic region. Pain symptoms, psychosocial, and quality-of-life measures were also assessed. All pain participants underwent laparoscopic excision of suspicious lesions to confirm endometriosis diagnosis by histologic evaluation. Results Patients included 18 with current, biopsy-proven endometriosis, 11 with pain only, and 20 healthy volunteers. The prevalence of sensitization as measured by regional allodynia and hyperalgesia was similar in both pain groups (83% and 82%) but much lower among healthy volunteers (15%, p<0.001). Nearly all women with pain had myofascial trigger points (94% and 91%). Adjusting for study group, those with high anxiety (OR=1.05, 95% CI:1.004–1.099; p=0.031) and depression (OR=1.06, 95% CI:1.005–1.113; p=0.032) scores were more likely to have sensitization. Pain patients with any history of endometriosis had the highest proportion of sensitization compared to the others (87% v 67% v 15%; p<0.001). Adjusting for any history of endometriosis, those with myofascial trigger points were most likely sensitized (OR=9.41, 95% CI:1.77–50.08, p=0.009). Conclusions Sensitization and myofascial trigger points were common in women with pain regardless of whether they had endometriosis at surgery. Those with any history of endometriosis were most likely to have sensitization. Traditional methods of classifying endometriosis-associated pain based on disease, duration, and anatomy are inadequate and should be replaced by a mechanism-based evaluation, as our study illustrates. PMID

  15. Paradoxical Double Binds in Human-Relations Training.

    ERIC Educational Resources Information Center

    Becvar, Raphael J.

    1978-01-01

    Paradoxical double binds are discussed relative to their efficacy in helping systematic human-relations trainees integrate the skills more quickly and with less pain and frustration. An explanation and examples of paradoxical double binds used in human-relations training are presented. (Author)

  16. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer.

    PubMed

    Kim, J Julie; Kurita, Takeshi; Bulun, Serdar E

    2013-02-01

    Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases.

  17. Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus

    PubMed Central

    Nakaoka, Hirofumi; Gurumurthy, Aishwarya; Hayano, Takahide; Ahmadloo, Somayeh; Omer, Waleed H; Yoshihara, Kosuke; Yamamoto, Akihito; Kurose, Keisuke; Enomoto, Takayuki; Akira, Shigeo; Hosomichi, Kazuyoshi; Inoue, Ituro

    2016-01-01

    Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage. PMID:27055116

  18. Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer

    PubMed Central

    Kim, J. Julie; Kurita, Takeshi

    2013-01-01

    Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases. PMID:23303565

  19. [Administration of MICRONIZED PALMITOYLETHANOLAMIDE (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis: preliminary results.

    PubMed

    Lo Monte, G; Soave, I; Marci, R

    2013-03-13

    Aim: Aim of the study was to evaluate the effectiveness of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis. Methods: Twenty-four patients with suspected endometriosis affected by severe pelvic pain were enrolled. All patients received two tablets a day of PEA 400 mg and 40 mg polydatin for 90 days consecutively. A Visual Analogic Scale was used for the assessment of the severity of global pain, dysmenorrhea, dyspareunia, dysuria and dischezia. A second questionnaire was submitted to patients to assess the quality of life. The compilation of a diary lead us to evaluate the monthly assumption of any painkillers. Patients were evaluated at the begin of the treatment and then monthly until the end of the study (90 days). The statistical analysis was performed by using the ANOVA for the analysis of variance. Results: Statistically significant results were found in relation to pelvic pain, dysmenorrhea and dyspareunia compared to the initial evaluation of patients. Results related to dysuria and dischezia were not statistically significant (P>0.05). The decrease in pelvic pain leads to an improvement of the quality of life of patients. A decreased assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) was also observed. Conclusion: PEA could be considered an effective supplement to conventional analgesic therapies in the management of pelvic pain related to endometriosis.

  20. Chromosome 1 in relation to human disease.

    PubMed Central

    Povey, S; Parrington, J M

    1986-01-01

    Chromosome 1 is thought to represent about 6% of the total human genome and the 85 loci so far identified may constitute about 1% of the genes present on this chromosome. The existence of at least 22 loci sufficiently polymorphic in Europeans to be useful as genetic markers has allowed the construction of an elementary genetic map. This permits comparisons with physical and chiasma maps and has demonstrated striking homologies between different regions of chromosome 1 and mouse chromosomes 1, 3, and 4. The existence of a map should be of great help in developing a more systematic approach to further mapping studies. A wide range of disease can be attributed to allelic variation on chromosome 1 and the homologies with the mouse may be useful in predicting the position of other genes involved in human disease. Rearrangements of this chromosome are a common finding in many different types of malignancy. Loss of material from the short arm and activation of one or more of the four oncogenes in this region may play an important role in the later stages of tumour development. Polymorphic markers of all kinds will be useful in the future for investigating the somatic events which have occurred during the malignant process. PMID:3519970

  1. Human milk and related oligosaccharides as prebiotics.

    PubMed

    Barile, Daniela; Rastall, Robert A

    2013-04-01

    Human milk oligosaccharides (HMO) are believed to have a range of biological activities beyond providing nutrition to the infant. Principal among these is that they may act as prebiotics. Prebiotics are dietary ingredients, usually oligosaccharides that provide a health benefit to the host mediated by the modulation of the human gut microbiota. While it is clear that such oligosaccharides may have potential applications in infants and adults alike, this potential is limited by the difficulties in manufacturing HMO. Consequently functional alternatives such as galacto-oligosaccharides (GOS) are under investigation. GOS are produced enzymatically from lactose for commercial use in food applications--including addition to infant formulae--as similar to breast milk oligosaccharides, they encourage a gut bacteria population that promotes health and reduces the incidence of intestinal infections. New methods for separation and concentration of complex, breast milk-like oligosaccharides from bovine milk industrial streams that contain only low amounts of these valuable oligosaccharides are providing the opportunity to investigate other viable sources of specific oligosaccharides for use as prebiotics in supplements or food products.

  2. Unsolved issues related to human mitochondrial diseases.

    PubMed

    Lombès, Anne; Auré, Karine; Bellanné-Chantelot, Christine; Gilleron, Mylène; Jardel, Claude

    2014-05-01

    Human mitochondrial diseases, defined as the diseases due to a mitochondrial oxidative phosphorylation defect, represent a large group of very diverse diseases with respect to phenotype and genetic causes. They present with many unsolved issues, the comprehensive analysis of which is beyond the scope of this review. We here essentially focus on the mechanisms underlying the diversity of targeted tissues, which is an important component of the large panel of these diseases phenotypic expression. The reproducibility of genotype/phenotype expression, the presence of modifying factors, and the potential causes for the restricted pattern of tissular expression are reviewed. Special emphasis is made on heteroplasmy, a specific feature of mitochondrial diseases, defined as the coexistence within the cell of mutant and wild type mitochondrial DNA molecules. Its existence permits unequal segregation during mitoses of the mitochondrial DNA populations and consequently heterogeneous tissue distribution of the mutation load. The observed tissue distributions of recurrent human mitochondrial DNA deleterious mutations are diverse but reproducible for a given mutation demonstrating that the segregation is not a random process. Its extent and mechanisms remain essentially unknown despite recent advances obtained in animal models.

  3. Association between endometriosis and the interleukin 1A (IL1A) locus

    PubMed Central

    Sapkota, Yadav; Low, Siew-Kee; Attia, John; Gordon, Scott D.; Henders, Anjali K.; Holliday, Elizabeth G.; MacGregor, Stuart; Martin, Nicholas G.; McEvoy, Mark; Morris, Andrew P.; Takahashi, Atsushi; Scott, Rodney J.; Kubo, Michiaki; Zondervan, Krina T.; Montgomery, Grant W.; Nyholt, Dale R.

    2015-01-01

    STUDY QUESTION Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk? SUMMARY ANSWER We found evidence for strong association between IL1A SNPs and endometriosis risk. WHAT IS KNOWN ALREADY Genetic factors contribute substantially to the complex aetiology of endometriosis and the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci. Recently, two small Japanese studies reported eight SNPs (rs6542095, rs11677416, rs3783550, rs3783525, rs3783553, rs2856836, rs1304037 and rs17561) at the IL1A gene locus as suggestively associated with endometriosis risk. There is also evidence of a link between inflammation and endometriosis. STUDY DESIGN, SIZE, DURATION We sought to further investigate the eight IL1A SNPs for association with endometriosis using an independent sample of 3908 endometriosis cases and 8568 controls of European and Japanese ancestry. The study was conducted between October 2013 and July 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS By leveraging GWA data from our previous multi-ethnic GWA meta-analysis for endometriosis, we imputed variants in the IL1A region, using a recent 1000 Genomes reference panel. After combining summary statistics for the eight SNPs from our European and Japanese imputed data with the published results, a fixed-effect meta-analysis was performed. An additional meta-analysis restricted to endometriosis cases with moderate-to-severe (revised American Fertility Society stage 3 or 4) disease versus controls was also performed. MAIN RESULTS AND THE ROLE OF CHANCE All eight IL1A SNPs successfully replicated at P < 0.014 in the European imputed data with concordant direction and similar size to the effects reported in the original Japanese studies. Of these, three SNPs (rs6542095, rs3783550 and rs3783525) also showed association with

  4. Perfluoroalkyl substances and endometriosis in US women in NHANES 2003-2006.

    PubMed

    Campbell, Stephanie; Raza, Masooma; Pollack, Anna Z

    2016-10-01

    Exposure to endocrine-active perfluoroalkyl substances (PFASs), is nearly ubiquitous, but data on the association between PFASs and endometriosis diagnosis are limited. We aimed to examine the relationship between PFASs and endometriosis. Women aged 20-50 years from the National Health and Nutrition Examination Survey (2003-2006) were selected (n=753). Serum PFAS levels were measured and endometriosis status was determined by self-report of doctor diagnosis. Weighted survey sampling logistic regression was used. Women reporting endometriosis were older (39.4 vs. 33.7 years), and more likely to be non-Hispanic white. Geometric mean levels of perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) were significantly higher among women reporting endometriosis. Endometriosis was associated with select quartiles of PFOA, PFNA, and PFOS. Sensitivity analyses had similar results but wider confidence intervals. These findings suggest that PFOA, PFNA, and PFOS may be of interest in future studies with improved endometriosis diagnostic criteria and prospectively measured exposure.

  5. Oocyte quality is decreased in women with minimal or mild endometriosis

    PubMed Central

    Xu, Bo; Guo, Nan; Zhang, Xiao-min; Shi, Wei; Tong, Xian-hong; Iqbal, Furhan; Liu, Yu-sheng

    2015-01-01

    Endometriosis, a pathological condition in which the endometrium grows outside the uterus, is one of the most common causes of female infertility; it is diagnosed in 25–40% of infertile women. The mechanism by which endometriosis affects the fertility of females remains largely unknown. We examined the ultrastructure of oocytes from patients with minimal or mild endometriosis and control females undergoing in vitro fertilization (IVF) treatment by transmission electron microscopy (TEM) to investigate the physiological significance of oocyte quality for patients with minimal or mild endometriosis. The TEM results revealed that the oocytes from women with minimal or mild endometriosis exhibited abnormal mitochondrial structure and decreased mitochondria mass. Quantitative real time PCR analysis revealed that the mitochondrial DNA copy number was significantly reduced in the oocytes from women with minimal or mild endometriosis compared with those of the control subjects. Our results suggest that decreased oocyte quality because of impaired mitochondrial structure and functions probably an important factor affecting the fertility of endometriosis patients. PMID:26022105

  6. Increased Risk of Endometriosis in Patients With Lower Genital Tract Infection

    PubMed Central

    Lin, Wu-Chou; Chang, Cherry Yin-Yi; Hsu, Yu-An; Chiang, Jen-Huai; Wan, Lei

    2016-01-01

    Abstract Endometriosis results from the ectopic invasion of endometrial glands and stroma in the peritoneal cavity. The exact etiology of endometriosis is still unknown. It has, however, been shown that there are higher numbers of Escherichia coli in menstrual blood, and higher endotoxin levels in menstrual fluid, as well as, in the peritoneal fluid of patients with endometriosis. In this study, we aimed to determine whether lower genital tract infections could increase the risk of endometriosis. We used the Taiwan National Health Insurance database to conduct a population-based cohort study. We included patients diagnosed with inflammatory diseases of the cervix, vagina, and vulva, and a control group comprising patients matched by age, sex, and comorbidities but without inflammatory diseases of the cervix, vagina, or vulva. A total of 79,512 patients were included in the inflammatory disease group and an equal number of control individuals were selected. The incidence of endometriosis (hazard ratio, 2.01; 95% confidence interval, 1.91–2.12; P < 0.001) was higher among patients than controls. Cox proportional hazards models showed that irrespective of comorbidities, lower genital tract infection was an independent risk factor for endometriosis. Patients with lower genital tract infections exhibit a substantially higher risk for developing endometriosis. PMID:26962775

  7. Migraine in women with chronic pelvic pain with and without endometriosis

    PubMed Central

    Karp, Barbara Illowsky; Sinaii, Ninet; Nieman, Lynnette K.; Silberstein, Stephen D.; Stratton, Pamela

    2012-01-01

    Objective To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis. Design Prospective study of headache, pelvic pain, and quality of life before laparoscopic surgery for pelvic pain. Endometriosis was diagnosed pathologically. Headaches were classified as migraine or non-migraine using International Headache Society criteria. Setting Clinical research hospital. Patient(s) 108 women in a clinical trial for chronic pelvic pain (NCT00001848). Intervention(s) Laparoscopy to diagnose endometriosis, assessment by neurologist to assess headaches. Main Outcome Measure(s) Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis. Headache frequency, severity and relationship to pelvic pain and endometriosis. Result(s) Lifetime prevalence of definite or possible migraine was 67% of women with chronic pelvic pain. An additional 8% met criteria for possible migraine. Migraine was no more likely in women with endometriosis than those without. Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone. Conclusion(s) Migraine headache is common in women with chronic pelvic pain, regardless of endometriosis, and contributes to disability in those with both conditions. The strong association suggests a common pathophysiology. PMID:21145540

  8. Teacher Leader Human Relations Skills: A Comparative Study

    ERIC Educational Resources Information Center

    Roby, Douglas E.

    2012-01-01

    In this study, 142 graduate school teachers working in schools throughout southwestern Ohio assessed their human relation skills. A human relations survey was used for the study, and results were compared with colleagues assessing the teachers in the study. The survey was developed using a Likert-type scale, and was based on key elements affecting…

  9. A Human Relations Approach to the Practice of Educational Leadership.

    ERIC Educational Resources Information Center

    Rebore, Ronald W.

    This book centers on the human-relation skills and knowledge that educational leaders need to lead public schools effectively. The purpose of the book is to help administrators and those studying to become administrators enhance their human-relations skills. The content and method of this book are centered on the first four of the six Interstate…

  10. Endometriosis Located Proximal to or Remote From the Uterus Differentially Affects Uterine Gene Expression.

    PubMed

    Naqvi, Hanyia; Mamillapalli, Ramanaiah; Krikun, Graciela; Taylor, Hugh S

    2016-02-01

    The mechanisms that lead to the altered uterine gene expression in women with endometriosis are poorly understood. Are these changes in gene expression mediated by proximity to endometriotic lesions or is endometriosis a systemic disease where the effect is independent of proximity to the uterus? To answer this question, we created endometriosis in a murine model either in the peritoneal cavity (proximal) or at a subcutaneous remote site (distal). The expression of several genes that are involved in endometrial receptivity (homeobox A10 [Hoxa10], homeobox A11 [Hoxa11], insulin-like growth factor binding protein 1 [Igfbp1], Kruppel-like factor 9 [Klf9], and progesterone receptor [Pgr]) was measured in the eutopic endometrium of mice transplanted with either proximal or distal endometriosis lesions. Decreased expression of Hoxa10, Igfbp1, Klf9, and total Pgr genes was observed in the eutopic endometrium of mice with peritoneal endometriosis. In the mice with distal lesions, overall expression of these genes was not as severely affected, however, Igfbp1 expression was similarly decreased and the effect on Pgr was more pronounced. Endometriosis does have a systemic effect that varies with distance to the end organ. However, even remote disease selectively and profoundly alters the expression of genes such as Pgr. This is the first controlled experiment demonstrating that endometriosis is not simply a local peritoneal disease. Selective alteration of genes critical for endometrial receptivity and endometriosis propagation may be systemic. Similarly, systemic effects of endometriosis on other organs may also be responsible for the widespread manifestations of the disease.

  11. Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan.

    PubMed

    Teng, Sen-Wen; Horng, Huann-Cheng; Ho, Chi-Hong; Yen, Ming-Shyen; Chao, Hsiang-Tai; Wang, Peng-Hui

    2016-11-01

    Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities.

  12. Disrupted cell cycle control in cultured endometrial cells from patients with endometriosis harboring the progesterone receptor polymorphism PROGINS.

    PubMed

    D'Amora, Paulo; Maciel, Thiago Trovati; Tambellini, Rodrigo; Mori, Marcelo A; Pesquero, João Bosco; Sato, Helio; Girão, Manoel João Batista Castello; Guerreiro da Silva, Ismael Dale Cotrim; Schor, Eduardo

    2009-07-01

    Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis. The cells from women with endometriosis that carried the PROGINS allele demonstrated increased proliferation, greater viability, and decreased apoptosis following progesterone treatment. In general, these parameters were very different as compared with those of women with endometriosis but without the PROGINS allele and women in the control group. This result indicates there is a reduced level of progesterone responsiveness in women who carry the PROGINS polymorphism. Because progesterone responsiveness is known to be an important characteristic of women with endometriosis, these data support the contention that the PROGINS polymorphism enhances the endometriosis phenotype.

  13. Relative sound localisation abilities in human listeners

    PubMed Central

    Wood, Katherine C.; Bizley, Jennifer K.

    2015-01-01

    Spatial acuity varies with sound-source azimuth, signal-to-noise ratio, and the spectral characteristics of the sound source. Here, the spatial localisation abilities of listeners were assessed using a relative localisation task. This task tested localisation ability at fixed angular separations throughout space using a two-alternative forced-choice design across a variety of listening conditions. Subjects were required to determine whether a target sound originated to the left or right of a preceding reference in the presence of a multi-source noise background. Experiment 1 demonstrated that subjects' ability to determine the relative location of two sources declined with less favourable signal-to-noise ratios and at peripheral locations. Experiment 2 assessed performance with both broadband and spectrally restricted stimuli designed to limit localisation cues to predominantly interaural level differences or interaural timing differences (ITDs). Predictions generated from topographic, modified topographic, and two-channel models of sound localisation suggest that for low-pass stimuli, where ITD cues were dominant, the two-channel model provides an adequate description of the experimental data, whereas for broadband and high frequency bandpass stimuli none of the models was able to fully account for performance. Experiment 3 demonstrated that relative localisation performance was uninfluenced by shifts in gaze direction. PMID:26328685

  14. Cesarean Scar Endometriosis: An Uncommon Surgical Complication on the Rise? Case Report and Literature Review

    PubMed Central

    Filali Adib, Abdelhai; Bezad, Rachid

    2017-01-01

    Endometriosis is defined by the presence and growth of ectopic functional endometrial tissue outside the uterus. Scar endometriosis has been described following obstetrical and gynecological surgery. It is a rare condition, though probably on the rise, due to the considerable increase of cesarean sections performed worldwide. Its physiopathology is complex; its symptomatology is rich and diverse but thorough clinical examination along with ultrasound imaging and potentially pretherapeutic cytologic evaluation are usually efficient in diagnosing the condition. Treatment is mostly surgical. We report the case of a cesarean section scar endometriosis, managed at a tertiary level center and emphasize the diagnosis and treatment options. PMID:28326210

  15. The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

    PubMed Central

    Hughes, C. L.; Foster, W. G.

    2015-01-01

    In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women's health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan. PMID:26064879

  16. Human papillomavirus related diseases in Malaysians.

    PubMed

    Cheah, P L

    1994-06-01

    The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.

  17. Human biomonitoring issues related to lead exposure.

    PubMed

    Nieboer, Evert; Tsuji, Leonard J S; Martin, Ian D; Liberda, Eric N

    2013-10-01

    Lead as a toxic environmental metal has been an issue of concern for 30-40 years. Even though the exposures experienced by the general public have been significantly reduced, so have the acceptable blood lead concentrations assessed to safeguard health (specifically of children). The impact of these concurrent changes are reviewed and discussed in terms of the following: blood lead as the primary biomarker of exposure; pertinent toxicokinetic issues including modelling; legacy and newer sources of this toxic metal; improvements in lead quantification techniques and its characterization (chemical forms) in exposure media; and in vivo markers of lead sources. It is concluded that the progress in the quantification of lead and its characterization in exposure media have supported the efforts to identify statistical associations of lead in blood and tissues with adverse health outcomes, and have guided strategies to reduce human exposure (especially for children). To clarify the role of lead as a causative factor in disease, greater research efforts in biomarkers of effect and susceptibility seem timely.

  18. [Ethics and laws related to human subject research].

    PubMed

    Chiu, Hui-Ju; Lee, Ya-Ling; Chang, Su-Fen

    2011-10-01

    Advances in medical technology rely on human subject research to test the effects on real patients of unproven new drugs, equipment and techniques. Illegal human subject research happens occasionally and has led to subject injury and medical disputes. Familiarity with the laws and established ethics related to human subject research can minimize both injury and disputes. History is a mirror that permits reflection today on past experience. Discussing the Nuremberg Code, the Declaration of Helsinki and Belmont Report, this article describes the laws, ethics, history and news related to human subject research as well as the current definition and characteristics of human subject research. Increasing numbers of nurses serve as research nurses and participate in human subject research. The authors hope this article can increase research nurse knowledge regarding laws and ethics in order to protect human research subjects adequately.

  19. Treatment efficacy for pain complaints in women with endometriosis of the lesser pelvis after laparoscopic electroablation vs. CO2 laser ablation.

    PubMed

    Posadzka, Ewa; Jach, Robert; Pityński, Kazimierz; Jablonski, Marcin Jacek

    2015-01-01

    Endometriosis is a chronic disease affecting mainly women of the reproductive age. Its most common manifestations include impaired fecundity, pelvic pain, and dyschezia. Laparoscopic removal of endometriotic foci remains to be the gold standard for the treatment of endometriosis. More effective techniques of endoscopic approach-among others, laser application-are continually being developed. The aim of the study was to evaluate the efficacy of laparoscopic treatment with the use of CO2 laser ablation vs. electroablation with regard to pain complaints in the affected patients. The study included 48 women (aged 22-42) with varying degrees of endometriosis of the lesser pelvis. The Numeric Rating Scale (NRS) was used to evaluate pain intensity before the surgery in all patients, followed by either laser ablation or electroablation of the endometriotic foci. The results of the laparoscopic treatment were monitored after 3 and 6 months postoperatively. p value of 0.05 was considered to be statistically significant. Patients from both groups reported less intensive pain before/during menstruation (dysmenorrhea) 6 months postoperatively, with more distinct tendency in the electroablation group (p = 0.004) as compared to the laser ablation group (p = 0.025). Despite the initial improvement reported at the 3-month checkup (p = 0.008), 6 months postoperatively, a statistically significant increase in pain intensity was noted in both groups (p = 0.016 and p = 0.032 for CO2 laser ablation and electroablation, respectively). Both surgical methods seem to be effective only in the treatment of endometriosis-related dysmenorrhea, whereas the intensity of other pain complaints (dyspareunia, dysuria, dyschezia, pelvic pain syndrome (PPS)) has remained on the same level.

  20. Disturbed estrogen and progesterone action in ovarian endometriosis.

    PubMed

    Smuc, Tina; Hevir, Neli; Ribic-Pucelj, Martina; Husen, Bettina; Thole, Hubert; Rizner, Tea Lanisnik

    2009-03-25

    Endometriosis is a very common disease in pre-menopausal women, where defective metabolism of steroid hormones plays an important role in its development and promotion. In the present study, we have examined the expression of 11 estrogen and progesterone metabolizing enzymes and their corresponding receptors in samples of ovarian endometriomas and control endometrium. Expression analysis revealed significant up-regulation of enzymes involved in estradiol formation (aromatase, sulfatase and all reductive 17beta-hydroxysteroid dehydrogenases) and in progesterone inactivation (AKR1C1 and AKR1C3). Among the estrogen and progesterone receptors, ERalpha was down-regulated, ERbeta was up-regulated, and there was no significant difference in expression of progesterone receptors A and B (PRAB). Our data indicate that several enzymes of estrogen and progesterone metabolism are aberrantly expressed in endometriosis, which can lead to increased local levels of mitogenic estradiol and decreased levels of protective progesterone. Changes in estrogen receptor expression suggest that estradiol may also act via non-estrogen receptor-mediated pathways, while expression of progesterone receptors still needs further investigation.

  1. Endometriosis in Italy: from cost estimates to new medical treatment.

    PubMed

    Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Petraglia, Felice

    2009-11-01

    Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which induced a chronic inflammatory reaction. The data collected from Italy showed that around 3 million women are affected by endoemtriosis and the condition was predominantly found in women of reproductive age (50% of women were in the 29-39 age range), only 25% of women were asymptomatic. The associated symptoms can create an impact in general physical, mental, and social well-being. Endometriosis is associated with severe dysmenorrhea, deep dyspareunia, chronic pelvic pain, ovulation pain, cyclical, or perimenstrual symptoms, with or without abnormal bleeding, infertility, and chronic fatigue. The annual cost for hospital admission can be estimated to be in a total around 54 million euros. The average time for right diagnosis is around 9 years still today and it follows a long and expensive diagnostic search. Therapies can be useful to relieve and sometimes solve the symptoms, encourage fertility, eliminate endometrial lesions, and restore the anatomy of the pelvis. For medical therapy, several different preparations (oral contraceptives, progestogenics, gestrinone, danazol, and GnRHa) and new options (GnRH antagonists, aromatase inhibitors, estrogen receptor beta agoinist, progesterone receptor modulators, angiogenesis inhibitors, and COX-2 selective inhibitors) are available.

  2. A Dynamic Conception of Humanity, Intercultural Relation and Cooperative Learning

    ERIC Educational Resources Information Center

    Noaparast, Khosrow Bagheri; Khosravi, Zohreh

    2010-01-01

    The main focus of this paper relates to the conceptualizations of human identity and intercultural relations needed for cooperative learning (CL) to occur. At one extreme, some have argued that the relation between different cultures should be conceptualized in terms of incommensurability. At the other extreme, a standardization and unification…

  3. Medical management of endometriosis: emerging evidence linking inflammation to disease pathophysiology.

    PubMed

    Bruner-Tran, K L; Herington, J L; Duleba, A J; Taylor, H S; Osteen, K G

    2013-04-01

    Progesterone action normally mediates the balance between anti-inflammatory and proinflammatory processes throughout the female reproductive tract. However, in women with endometriosis, endometrial progesterone resistance, characterized by alterations in progesterone responsive gene and protein expression, is now considered a central element in disease pathophysiology. Recent studies additionally suggest that the peritoneal microenvironment of endometriosis patients exhibits altered physiological characteristics that may further promote inflammation-driven disease development and progression. Within this review, we summarize our current understanding of the pathogenesis of endometriosis with an emphasis on the role that inflammation plays in generating not only the progesterone-resistant eutopic endometrium but also a peritoneal microenvironment that may contribute significantly to disease establishment. Viewing endometriosis from the emerging perspective that a progesterone resistant endometrium and an immunologically compromised peritoneal microenvironment are biologically linked risk factors for disease development provides a novel mechanistic framework to identify new therapeutic targets for appropriate medical management.

  4. Arg72Pro p53 polymorphism in Italian women: no association with endometriosis.

    PubMed

    Vietri, Maria Teresa; Molinari, Anna Maria; Iannella, Iolanda; Cioffi, Michele; Bontempo, Paola; Ardovino, Mario; Scaffa, Cono; Colacurci, Nicola; Cobellis, Luigi

    2007-11-01

    p53 codon 72 polymorphism in Italian women have a minor role in determining genetic susceptibility to endometriosis. The racial differences, in association with other risk factors, might be underlined in endometriotic disease.

  5. [Psychology and sexology are essential, from diagnosis to comprehensive care of endometriosis].

    PubMed

    Leroy, A; Azaïs, H; Garabedian, C; Bregegere, S; Rubod, C; Collier, F

    2016-06-01

    Endometriosis, defined by the presence of endometrial tissue outside the uterine cavity, is a common but often under diagnosed pathology. The clinical manifestations are varied (chronic pelvic pain, urinary or gastrointestinal symptoms) and can sometimes be very frustrated, delaying the diagnosis. This delay in diagnosis can be a high source of stress responsible for an important psychological impact in these patients, having a sense of misunderstanding and neglect of the medical profession. This climate of stress and anxiety can cause alteration of behavior including sexual disorders. In addition, endometriosis can be revealed as part of an infertility evaluation, and the patient and the couple can already be affected by this situation. The clinical and psychological impact of endometriosis inevitably leads to an impairment of patient's quality of life and sexuality. The objective of this article is to show the psychological consequences of endometriosis and its impact on sexuality, in order to highlight this essential aspect for a comprehensive care of patients.

  6. Endometriosis in a post-laparoscopic scar--case report and literature review.

    PubMed

    Chmaj-Wierzchowska, Karolina; Pieta, Beata; Czerniak, Tomasz; Opala, Tomasz

    2014-05-01

    Endometriosis is an estrogen-dependent, chronic disease consisting in implantation and hyperplasia of the endometrium outside of the uterine cavity Endometriosis in post-laparoscopic scars applies to approx. 0.5-7% of the extraorganic locations of the disease. The purpose of the paper was to describe medical management and literature review for endometriosis in a post-laparoscopic scar. Two lesions located near the insertion site for the lower trocars were removed along with the border of healthy tissue. At the time of publication of this paper the patient did not report any complaints. In conclusion, each limited lesion in the subcutaneous tissue, with pain intensifying during menstruation, should suggest an initial diagnosis of scar endometriosis, regardless of patient age and type of surgery

  7. [Ovarian endometriosis involving the intestine with "ab ++estrinseco" stenosis of the sigmoid].

    PubMed

    Giacomelli, L; Pulcini, A; Leone, L; Fabrizio, G; Granai, A V; Messinetti, S

    1994-03-01

    The Authors report a case of ovarian endometriosis causing an "Ab extrinseco" sigmoid stenosis. The histogenesis as well as different possibilities of treatment, i.e. medical and surgical, are discussed.

  8. How Many People Are Affected by or at Risk for Endometriosis?

    MedlinePlus

    ... Research Information Clinical Trials Resources and Publications How many people are affected by or at risk for endometriosis? Skip sharing on social media links Share this: Page Content Because some women ...

  9. [Digestive endometriosis. Apropos of 5 cases of intestinal involvement and resection].

    PubMed

    Blanchot, J; Jacquemard, F; Letoquart, J P; Marcorelles, P; Mambrini, A; Giraud, J R

    1990-05-01

    The authors report 5 cases of intestinal endometriosis which required resection. They review the pathological characteristics and attempt to define the while accepting that the indications for resection should be extremely limited from both gynecological and intestinal viewpoints.

  10. Diver Relative UUV Navigation for Joint Human-Robot Operations

    DTIC Science & Technology

    2013-09-01

    NAVIGATION FOR JOINT HUMAN- ROBOT OPERATIONS by Andrew T. Streenan September 2013 Thesis Advisor: Noel Du Toit Second Reader: Doug...COVERED Master’s Thesis 4. TITLE AND SUBTITLE DIVER RELATIVE UUV NAVIGATION FOR JOINT HUMAN- ROBOT OPERATIONS 5. FUNDING NUMBERS 6. AUTHOR(S...here: a robotic diver assistant that enables close-quarters robotic operations with human divers. A robotic diver assistant has the potential to

  11. Krüppel-Like Factor 13 Deficiency in Uterine Endometrial Cells Contributes to Defective Steroid Hormone Receptor Signaling but Not Lesion Establishment in a Mouse Model of Endometriosis.

    PubMed

    Heard, Melissa E; Velarde, Michael C; Giudice, Linda C; Simmen, Frank A; Simmen, Rosalia C M

    2015-06-01

    Krüppel-like Factor (KLF) 13 and the closely related KLF9 are members of the Sp/KLF family of transcription factors that have collectively emerged as essential regulators of tissue development, differentiation, proliferation, and programmed cell death. Steroid hormone-responsive tissues express multiple KLFs that are linked to progesterone receptor (PGR) and estrogen receptor (ESR) actions either as integrators or as coregulators. Endometriosis is a chronic disease characterized by progesterone resistance and dysregulated estradiol signaling; nevertheless, distinct KLF members' contributions to endometriosis remain largely undefined. We previously demonstrated promotion of ectopic lesion establishment by Klf9 null endometrium in a mouse model of endometriosis. Here we evaluated whether KLF13 loss of expression in endometrial cells may equally contribute to lesion formation. KLF13 transcript levels were lower in the eutopic endometria of women with versus women without endometriosis at menstrual midsecretory phase. In wild-type (WT) mouse recipients intraperitoneally administered WT or Klf13 null endometrial fragments, lesion incidence did not differ with donor genotype. No differences were noted for lesion volume, number, proliferation status, and apoptotic index as well. Klf13 null lesions displayed reduced total PGR and ESR1 (RNA and immunoreactive protein) and altered expression of several PGR and ESR1 target genes, relative to WT lesions. Unlike for Klf9 null lesions, changes in transcript levels for PGR-A, ESR1, and Notch/Hedgehog-associated pathway components were not observed for Klf13 null lesions. Results demonstrate lack of a causative relationship between endometrial KLF13 deficiency and lesion establishment in mice, and they support the broader participation of multiple signaling pathways, besides those mediated by steroid receptors, in the pathology of endometriosis.

  12. Retroperitoneal Endometriosis: A Possible Cause of False Positive Finding at 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

    PubMed Central

    Maffione, Anna Margherita; Panzavolta, Riccardo; Lisato, Laura Camilla; Ballotta, Maria; D'Isanto, Mariangela Zanforlini; Rubello, Domenico

    2015-01-01

    Endometriosis is a frequent and clinically relevant problem in young women. Laparoscopy is still the gold standard for the diagnosis of endometriosis, but frequently both morphologic and functional imaging techniques are involved in the diagnostic course before achieving a conclusive diagnosis. We present a case of a patient affected by infiltrating retroperitoneal endometriosis falsely interpreted as a malignant mass by contrast-enhanced magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography. PMID:26097425

  13. The Relation Between Audition and Vision in the Human Newborn

    ERIC Educational Resources Information Center

    Mendelson, Morton J.; Haith, Marshall M.

    1976-01-01

    Four studies were conducted to investigate the relation between audition and vision in the human newborn. In all four studies visual activity was recorded with infrared corneal-reflection techniques in 1- to 4-day-old infants. (MS)

  14. A Human Relations Approach to Custodial and Maintenance Training.

    ERIC Educational Resources Information Center

    Parker, Woodrow M.; And Others

    1983-01-01

    Describes a training program for residence hall custodial and maintenance supervisors and staff which combines human relations and technical skills. The sessions dealt with communication skills, leadership strategies, performance appraisal, self-understanding, advancement, and fringe benefits. (JAC)

  15. Anisakiasis and intestinal endometriosis: under-recognized conditions in the differential diagnosis of acute abdomen.

    PubMed

    Sánchez Justicia, Carlos; Granero Peiró, Lucia; Arabe Paredes, Jorge Ali

    2017-01-01

    Anisakiasis and endometriosis is rare cause of intestinal obstruction and even perforation, the latter being extremely rare. We report the case of a patient with intestinal obstruction that progress to perforation and whose differential diagnosis is complex. The interest in this clinical case lies in the unexpected histology of the surgical specimen after the intervention of the patient, because the intestinal endometriosis as intestinal anisakiasis are rare entities that make diagnosis difficult.

  16. The International Endometriosis Evaluation Program (IEEP Study) – A Systematic Study for Physicians, Researchers and Patients

    PubMed Central

    Burghaus, S.; Fehm, T.; Fasching, P. A.; Blum, S.; Renner, S. K.; Baier, F.; Brodkorb, T.; Fahlbusch, C.; Findeklee, S.; Häberle, L.; Heusinger, K.; Hildebrandt, T.; Lermann, J.; Strahl, O.; Tchartchian, G.; Bojahr, B.; Porn, A.; Fleisch, M.; Reicke, S.; Füger, T.; Hartung, C.-P.; Hackl, J.; Beckmann, M. W.; Renner, S. P.

    2016-01-01

    Introduction: Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. Material and Methods: To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. Results: A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. Conclusion: The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers. PMID:27582581

  17. Patients’ report on how endometriosis affects health, work, and daily life

    PubMed Central

    Fourquet, Jessica; Gao, Xin; Zavala, Diego; Orengo, Juan C.; Abac, Sonia; Ruiz, Abigail; Laboy, Joaquín; Flores, Idhaliz

    2009-01-01

    NARRATIVE ABSTRACT The objective of this study was to assess the burden of endometriosis by obtaining Patient Reported Outcome (PRO) data describing the experience of living with this disease. Survey data from one hundred and seven women with self-reported, surgically diagnosed endometriosis showed that living with this disease may be characterized by physical limitations that disrupt health, work and daily life. PMID:19926084

  18. Oxidative Stress Statues in Serum and Follicular Fluid of Women with Endometriosis

    PubMed Central

    Nasiri, Nahid; Moini, Ashraf; Eftekhari-Yazdi, Poopak; Karimian, Leila; Salman-Yazdi, Reza; Arabipoor, Arezoo

    2017-01-01

    Objective This study aimed to evaluate the levels of two oxidative stress (OS) markers including lipid peroxide (LPO) and total antioxidant capacity (TAC) in both serum and follicular fluid (FF) of women with endometriosis after puncture. Materials and Methods In this cross-sectional study, a total number of sixty-three women younger than 40 years old with laparoscopy (gold standard for endometriosis diagnosis) indication underwent in vitro fertilization (IVF) program in the Royan Institute, Tehran, Iran from September 2013 to October 2014. About forty-three patients were diagnosed with endometriosis after laparoscopy. Blood and FF from the leading follicle in each stimulated ovary were obtained at the time of egg retrieval; samples were centrifuged and frozen until assessment. At the time of sample assessment, serum and FF samples were evaluated for the levels of LPO and TAC on spectrophotometery. Results We observed that women with endometriosis had significantly higher LPO and lower TAC levels in the serum and FF as compared with the control group (P<0.05). Conclusion It has observed that FF of women with endometriosis, regardless of disease stage, increases the proliferation power of endometrial cells in vitro, we presume that inflammatory reactions-induced OS in ovary may be responsible for proliferation induction ability in FF obtained from women with endometriosis. PMID:28042542

  19. Intestinal metaplasia of appendiceal endometriosis is not uncommon and may mimic appendiceal mucinous neoplasm.

    PubMed

    Vyas, Monika; Wong, Serena; Zhang, Xuchen

    2017-01-01

    Endometriosis of the appendix can be an incidental finding or a cause of appendicitis, intussusception, perforation or retention mucocele. Intestinal metaplasia of appendiceal endometriosis may occur, which can lead to a misdiagnosis of low-grade appendiceal mucinous neoplasm. On a retrospective search of the pathology database from 2001 to 2015, we identified 78 appendiceal endometriosis cases and intestinal metaplasia was present in 10/78 (13%) cases. In most of the cases (90%), the foci of intestinal metaplasia were mainly localized close to the mucosa. Intestinal and endometrial hybrid glands were present in 9/10 (90%) cases. These cases were often associated with marked appendiceal distortion, luminal obliteration and mass formation, causing concern for a mucinous neoplasm clinically and pathologically. Our findings indicate that intestinal metaplasia in appendiceal endometriosis is not an uncommon phenomenon, which can be mistaken for a mucinous neoplasm. Endometriosis should be kept in mind when a diagnosis of appendiceal mucinous neoplasm is made, especially in a young woman with a clinical history of endometriosis.

  20. Protocol for developing, disseminating and implementing a core outcome set for endometriosis

    PubMed Central

    Hirsch, Martin; Duffy, James M N; Barker, Claire; Hummelshoj, Lone; Johnson, Neil P; Mol, Ben; Khan, Khalid S; Farquhar, Cindy

    2016-01-01

    Introduction Endometriosis is a common gynaecological disease characterised by pain and subfertility. Randomised controlled trials evaluating treatments for endometriosis have reported many different outcomes and outcome measures. This variation restricts effective data synthesis limiting the usefulness of research to inform clinical practice. To address these methodological concerns, we aim to develop, disseminate and implement a core outcome set for endometriosis engaging with key stakeholders, including healthcare professionals, researchers and women with endometriosis. Methods and analysis An international steering group has been established, including healthcare professionals, researchers and patient representatives. Potential outcomes identified from a systematic review of the literature will be entered into a modified Delphi method. Key stakeholders will be invited to participate including healthcare professionals, researchers and women with endometriosis. Participants will be invited to score individual outcomes on a nine-point Likert scale anchored between 1 (not important) and 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group converge towards consensus, ‘core’, outcomes. High-quality outcome measures will be associated with core outcomes. Ethics and dissemination The implementation of a core outcome set for endometriosis within future clinical trials, systematic reviews and clinical guidelines will enhance the availability of comparable data to facilitate evidence-based patient care. This study was prospectively registered with Core Outcome Measures in Effectiveness Trials Initiative; number: 691. PMID:28003300

  1. Genomic signatures of diet-related shifts during human origins.

    PubMed

    Babbitt, Courtney C; Warner, Lisa R; Fedrigo, Olivier; Wall, Christine E; Wray, Gregory A

    2011-04-07

    There are numerous anthropological analyses concerning the importance of diet during human evolution. Diet is thought to have had a profound influence on the human phenotype, and dietary differences have been hypothesized to contribute to the dramatic morphological changes seen in modern humans as compared with non-human primates. Here, we attempt to integrate the results of new genomic studies within this well-developed anthropological context. We then review the current evidence for adaptation related to diet, both at the level of sequence changes and gene expression. Finally, we propose some ways in which new technologies can help identify specific genomic adaptations that have resulted in metabolic and morphological differences between humans and non-human primates.

  2. Genomic signatures of diet-related shifts during human origins

    PubMed Central

    Babbitt, Courtney C.; Warner, Lisa R.; Fedrigo, Olivier; Wall, Christine E.; Wray, Gregory A.

    2011-01-01

    There are numerous anthropological analyses concerning the importance of diet during human evolution. Diet is thought to have had a profound influence on the human phenotype, and dietary differences have been hypothesized to contribute to the dramatic morphological changes seen in modern humans as compared with non-human primates. Here, we attempt to integrate the results of new genomic studies within this well-developed anthropological context. We then review the current evidence for adaptation related to diet, both at the level of sequence changes and gene expression. Finally, we propose some ways in which new technologies can help identify specific genomic adaptations that have resulted in metabolic and morphological differences between humans and non-human primates. PMID:21177690

  3. Surgery for endometriosis-associated infertility: do we exaggerate the magnitude of effect?

    PubMed Central

    Rizk, B.; Turki, R.; Lotfy, H.; Ranganathan, S.; Zahed, H.; Freeman, A.R.; Shilbayeh, Z.; Sassy, M.; Shalaby, M.; Malik, R.

    2015-01-01

    Objective: Surgery remains the mainstay in the diagnosis and management of endometriosis. The number of surgeries performed for endometriosis worldwide is ever increasing, however do we have evidence for improvement of infertility after the surgery and do we exaggerate the magnitude of effect of surgery when we counsel our patients? The management of patients who failed the surgery could be by repeat surgery or assisted reproduction. What evidence do we have for patients who fail assisted reproduction and what is their best chance for achieving pregnancy? Material and methods: In this study we reviewed the evidence-based practice pertaining to the outcome of surgery assisted infertility associated with endometriosis. Manuscripts published in PubMed and Science Direct as well as the bibliography cited in these articles were reviewed. Patients with peritoneal endometriosis with mild and severe disease were addressed separately. Patients who failed the primary surgery and managed by repeat or assisted reproduction technology were also evaluated. Patients who failed assisted reproduction and managed by surgery were also studied to determine of the best course of action. Results: In patients with minimal and mild pelvic endometriosis, excision or ablation of the peritoneal endometriosis increases the pregnancy rate. In women with severe endometriosis, controlled trials suggested an improvement of pregnancy rate. In women with ovarian endometrioma 4 cm or larger ovarian cystectomy increases the pregnancy rate, decreases the recurrence rate, but is associated with decrease in ovarian reserve. In patients who have failed the primary surgery, assisted reproduction appears to be significantly more effective than repeat surgery. In patients who failed assisted reproduction, the management remains to be extremely controversial. Surgery in expert hands might result in significant improvement in pregnancy rate. Conclusion: In women with minimal and mild endometriosis, surgical

  4. Therapeutic Affordances of Online Support Group Use in Women With Endometriosis

    PubMed Central

    2016-01-01

    Background The Internet has provided women living with endometriosis new opportunities to seek support online. Online support groups may provide a range of therapeutic affordances that may benefit these women. Objective To examine the presence of therapeutic affordances as perceived by women who use endometriosis online support groups. Methods Sixty-nine women (aged 19-50 years, mean 34.2 years; 65.2% (45/69) United Kingdom, 21.7% (15/69) United States) participated in a Web-based interview exploring online support group use. Participants had been using online support groups for an average of 2 years and 4 months (range = 1 month to 14 years, 9 months). Responses were analyzed using inductive thematic analysis. Results The analysis revealed 4 therapeutic affordances related to online support group use: (1) “connection,” that is, the ability to connect in order to support each other, exchange advice, and to try to overcome feelings of loneliness; (2) “exploration,” that is, the ability to look for information, learn, and bolster their knowledge; (3) “narration,” that is, the ability to share their experiences, as well as read about the experiences of others; and (4) “self-presentation,” that is, the ability to manage how they present themselves online. The associated outcomes of use were predominantly positive, such as reassurance and improved coping. However, a number of negative aspects were revealed including the following: concerns about the accuracy of information, arguments between members, overreliance on the group, becoming upset by negative experiences or good news items, and confidentiality of personal information. Conclusions Our findings support the previously proposed SCENA (Self-presentation, Connection, Exploration, Narration, and Adaptation) model and reveal a range of positive aspects that may benefit members, particularly in relation to reassurance and coping. However, negative aspects need to be addressed to maximize the potential

  5. [Morphologic characteristics of the endometrium in women with endometriosis].

    PubMed

    Skopichev, V G; Savitkiĭ, G A; Gorbushin, S M

    1998-01-01

    It was established that in accordance with certain phases of sexual cycle (menstrual cycle in women and estral cycle in rats) on the background of hormone action at follicular and luteal phase the surface of epitheliocytes acquires specific relief (formation and degradation of microvilli appropriately in first and second halves of the cycle, accordingly). Disturbance of cyclic change of the relief of apical surface of epitheliocytes of the endometrium, persistence of high binding activity of the cationic dye and formation of intercellular clefts were demonstrated in developing endometriosis, which significantly interferes with the reproductive function. This was suggested to be an unfavourable result of cytotoxic effect of autoimmune processes that develop due to implantation of cells of endometrium in abdominal cavity and initiation of cooperative cellular response, which seems to be morphologically demonstrated by significant increase in number of macrophages in tissues of the uterus and in menstrual discharge.

  6. Incisional endometriosis: diagnosed by fine needle aspiration cytology.

    PubMed

    Veda, P; Srinivasaiah, M

    2010-07-01

    Incisional endometriosis (IE) is a rare entity reported in 0.03-1.08% of women following obstetric or gynecologic surgeries. Most cases reported in literature have appeared after cesarean sections and were often clinically mistaken for hernia, abscess, suture granuloma or lipoma. We hereby report a case of IE following a second trimester hysterotomy, which was diagnosed by fine needle aspiration cytology (FNAC). Our patient was 26 years old, presenting with a mass over anterior abdominal wall, associated with incapacitating pain during each menstrual cycle. FNAC showed epithelial cells, stromal cells and hemosiderin laden macrophages. Based on the typical history, clinical and cytological features, the diagnosis of IE was established. Wide surgical excision was done and the resulting rectus sheath defect was repaired. Patient was followed for 6 months during which time she was symptom free. This article also reviews the spectrum of cytological features and the rare possibility of malignant transformation that can occur in IE.

  7. The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis.

    PubMed

    Fang, Fang; Gong, Lili; Wang, Xiaojuan; Zhang, Ling

    2015-09-01

    The vascular endothelial growth factor (VEGF) is one of the most important candidate genes for the development of endometriosis, and VEGF genetic polymorphisms might be potentially associated with endometriosis risk. However, the results still remain controversial. The objective of this study aimed to perform a comprehensive meta-analysis to explore a better understanding of the effects of VEGF +405G>C genetic polymorphism on the risk of endometriosis. A total of eleven eligible studies were eventually identified in this meta-analysis, including 2829 endometriosis cases and 2947 controls. In the overall analysis, no significant association between the VEGF +405G>C genetic polymorphism and the risk of endometriosis was detected in all genetic models (for homozygote comparison [CC versus vs. GG]: OR = 1.21, 95% CI 0.67-2.19, P = 0.537; for heterozygote comparison [CG vs. GG]: OR = 1.16, 95% CI 0.86-1.56, P = 0.348; for dominant comparison CC/CG vs. GG: OR = 1.10, 95% CI 0.93-1.30, P = 0.263; for recessive comparison [CC vs. CG/GG]: OR = 1.03, 95% CI 0.73-1.47, P = 0.857; allele comparison [C vs. G]: OR = 0.99, 95% CI 0.70-1.40, P = 0.962). In the subgroup analysis by ethnicities, there was no significant association between VEGF +405G>C genetic polymorphism and endometriosis risk in Asians and/or Caucasians under all genetic models (all P-values >0.05). No publication bias was observed in this study. This meta-analysis supports that the VEGF +405G>C genetic polymorphism is not significant associated with the risk of endometriosis.

  8. Glycosaminoglycans in the Human Cornea: Age-Related Changes

    PubMed Central

    Pacella, Elena; Pacella, Fernanda; De Paolis, Giulio; Parisella, Francesca Romana; Turchetti, Paolo; Anello, Giulia; Cavallotti, Carlo

    2015-01-01

    AIM To investigate possible age-related changes in glycosaminoglycans (GAGs) in the human cornea. The substances today called GAGs were previously referred to as mucopolysaccharides. METHODS Samples of human cornea were taken from 12 younger (age 21 ± 1.2) and 12 older (age 72 ± 1.6) male subjects. Samples were weighed, homogenized, and used for biochemical and molecular analyses. All the quantitative results were statistically analyzed. RESULTS The human cornea appears to undergo age-related changes, as evidenced by our biochemical and molecular results. The total GAG and hyaluronic acid counts were significantly higher in the younger subjects than in the older subjects. The sulfated heavy GAGs, such as chondroitin, dermatan, keratan, and heparan sulfate, were lower in the younger subjects than in the older subjects. DISCUSSION GAGs of the human cornea undergo numerous age-related changes. Their quantity is significantly altered in the elderly in comparison with younger subjects. GAGs play an important role in age-related diseases of the human cornea. PMID:25674020

  9. Statins as Targeted "Magical Pills" for the Conservative Treatment of Endometriosis: May Potential Adverse Effects on Female Fertility Represent the "Dark Side of the Same Coin"? A Systematic Review of Literature.

    PubMed

    Vitagliano, Amerigo; Noventa, Marco; Quaranta, Michela; Gizzo, Salvatore

    2016-04-01

    The aim of the study was to analyze all the available evidence from both in vitro and in vivo studies regarding the efficacy of statin therapy in the treatment of endometriosis, evaluating the potential efficacy, side effects, and contraindications of their administration in humans. We focused on defining the potential benefits that the administration of statins may have on patients affected by endometriosis and the possible adverse effects of such a therapy on ovarian function and fertility profile. According to our article selection criteria, we included in the review in vitro and in vivo studies performed on human or animal models. The systematic review of literature identified 24 eligible articles, 12 of which reported evidence regarding the effects of statins on endometrial/endometriotic cells and 12 regarding their effects on ovarian function and fertility. All articles seem to emphasize the utility of statin administration in the treatment of endometriosis due to their anti-proliferative/proapoptotic effects, their ability to reduce cell viability and migration, and the inhibition of angiogenesis and anti-inflammatory activities. Regarding the potential adverse effects on gonadal activities, steroidogenesis and fertility function, no conclusive data were collected in human models (excluding women affected by polycystic ovary syndrome in which significant decline of androgen levels was reported after statin treatment), while contrasting results were reported by studies conducted in in vitro and in vivo in animal models. Despite evidence supporting statins as the potential therapeutic agent for a targeted conservative treatment of endometriosis, the uncertainties regarding their impact on gonadal function may not define them as an appropriate therapy for all young fertile women.

  10. Glaucoma related Proteomic Alterations in Human Retina Samples

    PubMed Central

    Funke, Sebastian; Perumal, Natarajan; Beck, Sabine; Gabel-Scheurich, Silke; Schmelter, Carsten; Teister, Julia; Gerbig, Claudia; Gramlich, Oliver W.; Pfeiffer, Norbert; Grus, Franz H.

    2016-01-01

    Glaucoma related proteomic changes have been documented in cell and animal models. However, proteomic studies investigating on human retina samples are still rare. In the present work, retina samples of glaucoma and non-glaucoma control donors have been examined by a state-of-the-art mass spectrometry (MS) workflow to uncover glaucoma related proteomic changes. More than 600 proteins could be identified with high confidence (FDR < 1%) in human retina samples. Distinct proteomic changes have been observed in 10% of proteins encircling mitochondrial and nucleus species. Numerous proteins showed a significant glaucoma related level change (p < 0.05) or distinct tendency of alteration (p < 0.1). Candidates were documented to be involved in cellular development, stress and cell death. Increase of stress related proteins and decrease of new glaucoma related candidates, ADP/ATP translocase 3 (ANT3), PC4 and SRFS1-interacting protein 1 (DFS70) and methyl-CpG-binding protein 2 (MeCp2) could be documented by MS. Moreover, candidates could be validated by Accurate Inclusion Mass Screening (AIMS) and immunostaining and supported for the retinal ganglion cell layer (GCL) by laser capture microdissection (LCM) in porcine and human eye cryosections. The workflow allowed a detailed view into the human retina proteome highlighting new molecular players ANT3, DFS70 and MeCp2 associated to glaucoma. PMID:27425789

  11. Dioxin/polychlorinated biphenyl body burden, diabetes and endometriosis: findings in a population-based study in Belgium.

    PubMed

    Fierens, Sébastien; Mairesse, Hélène; Heilier, Jean-François; De Burbure, Claire; Focant, Jean-François; Eppe, Gauthier; De Pauw, Edwin; Bernard, Alfred

    2003-01-01

    Dioxins and polychlorinated biphenyls (PCBs) are persistent organic pollutants widely distributed in the food chain, which is the main source of human exposure. Their effects on human health at background exposure levels are still poorly understood. Recent epidemiological evidence suggests a possible association between these pollutants and diabetes. We report here the results of a population-based study in Belgium on 257 (142 women and 115 men) environmentally exposed subjects, including 10 cases of endometriosis and nine cases of diabetes. Seventeen 2,3,7,8-polychlorinated dibenzodioxins/dibenzofurans (PCDD/Fs or dioxins), four coplanar PCBs (International Union of Pure and Applied Chemistry [IUPAC] nos 77, 81, 126 and 169) and 12 PCB markers (IUPAC nos 3, 8, 28, 52, 101, 118, 138, 153, 180, 194, 206 and 209) were quantified in serum fat from fasting blood samples in order to estimate the body burden of these pollutants. Whilst no difference was found between women with endometriosis and their controls, diabetic patients had significantly increased serum levels of dioxins, coplanar PCBs and the 12 PCB markers. After adjustment for age and other covariates, serum total toxic equivalent activity (sum of PCDD/Fs and coplanar PCBs) and 12 PCB marker concentrations in diabetics were 62% (p = 0.0005) and 39% (p = 0.0067) higher, respectively, than in controls. The risk of diabetes was significantly increased in subjects in the top decile for adjusted concentrations of dioxins (odds ratio 5.1, 95% confidence interval [CI] 1.18-21.7), coplanar PCBs (odds ratio 13.3, 95% CI 3.31-53.2) or 12 PCB markers (odds ratio 7.6, 95% CI 1.58-36.3). These findings warrant further studies to assess the significance of the associations between diabetes and environmental exposure to polychlorinated pollutants.

  12. Endometrial stromal progesterone receptor-A/progesterone receptor-B ratio: no difference between women with and without endometriosis.

    PubMed

    Gentilini, Davide; Vigano, Paola; Vignali, Michele; Busacca, Mauro; Panina-Bordignon, Paola; Caporizzo, Elvira; Di Blasio, Anna Maria

    2010-09-01

    The aim of the present study was to investigate whether alterations of the P receptor-A/P receptor-B ratio could be considered an etiopathogenetic factor for endometriosis. We failed to observe statistically significant differences in both P receptor-A/P receptor-B messenger RNA and protein ratio between endometrial stromal cells derived from women with and without endometriosis.

  13. Endometriosis Might Be Inversely Associated with Developing Chronic Kidney Disease: A Population-Based Cohort Study in Taiwan

    PubMed Central

    Huang, Ben-Shian; Chang, Wen-Hsun; Wang, Kuan-Chin; Huang, Nicole; Guo, Chao-Yu; Chou, Yiing-Jen; Huang, Hsin-Yi; Chen, Tzeng-Ji; Lee, Wen-Ling; Wang, Peng-Hui

    2016-01-01

    This study was conducted to determine the risk of chronic kidney disease (CKD) among women with endometriosis in Taiwan. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan. A total of 27,973 women with a diagnosis of endometriosis and 27,973 multivariable-matched controls (1:1) from 2000 to 2010 were selected. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of CKD among women with endometriosis. The incidence rates (IR, per 10,000 person-years) of CKD among women with and without endometriosis were 4.64 and 7.01, respectively, with a significantly decreased risk of CKD (crude HR 0.65, 95% CI 0.53–0.81; adjusted HR 0.69, 95% CI 0.56–0.86) among women with endometriosis. The IR of CKD progressively increased with age, but the trend of lower CKD risk among women with endometriosis was consistent. However, the lower risk of CKD in women with endometriosis was no longer statistically significant after adjusting for menopausal status (adjusted HR 0.85, 95% CI 0.65–1.10). The results suggest that endometriosis is inversely associated with CKD, but this effect was mediated by menopause. The possible mechanism of this association is worthy of further evaluation. PMID:27399682

  14. Length of Menstrual Cycle and Risk of Endometriosis: A Meta-Analysis of 11 Case-Control Studies.

    PubMed

    Wei, Ming; Cheng, Yanfei; Bu, Huaien; Zhao, Ye; Zhao, Wenli

    2016-03-01

    Endometriosis is a complex disease that affects a large number of women worldwide and may cause pain and infertility. To systematically review published studies evaluating the relationship between menstrual cycle length and risk of endometriosis. We searched the Cochrane Library, PubMed, Web of Science, and EMBASE in databases in July 2014 using the keywords "case-control studies," "epidemiologic determinants," "risk factors," "menstrual cycle," "menstrual length," "menstrual character," and "endometriosis." We included case-control studies published in English that investigated cases of surgically confirmed endometriosis and examined the relationship between endometriosis risk and menstrual cycle. Eleven articles that met the inclusion criteria included data of 3392 women with endometriosis and 5006 controls. Fixed-effects and random-effects models were used for the evaluation. For the association of risk of endometriosis and menstrual cycle length shorter than or equal to 27 days (SEQ27) or length longer than or equal to 29 days (LEQ29), the odds ratio was 1.22 (95% confidence interval [CI]: 1.05-1.43) and 0.68 (95% CI: 0.48-0.96), respectively. In conclusion, this meta-analysis suggests that menstrual cycle length SEQ27 increase the risk of endometriosis and cycle length LEQ29 decrease the risk.

  15. Pericardial, pleural and diaphragmatic endometriosis in association with pelvic peritoneal and bowel endometriosis: a case report and review of the literature.

    PubMed

    Ceccaroni, Marcello; Roviglione, Giovanni; Rosenberg, Piergiorgio; Pesci, Anna; Clarizia, Roberto; Bruni, Francesco; Zardini, Claudio; Ruffo, Giacomo; Placci, Angelo; Crippa, Stefano; Minelli, Luca

    2012-06-01

    Diaphragmatic endometriosis is a rare entity, often asymptomatic, which has been described only in small series. It is almost always associated with severe pelvic involvement. The most plausible theory about this condition is based on retrograde menstruation and subsequent transportation of viable cells in peritoneal fluid from the pelvis up the right gutter to the right hemidiaphragm, thus demonstrating its asymmetric distribution on the diaphragm. Pre-operative diagnosis is poorly supported by imaging techniques. In most cases, it is an incidental finding because the lesions may hide behind the right hepatic lobe. In that case it cannot be easily demonstrated with a laparoscope from an umbilical port. Symptomatic diaphragmatic endometriosis is associated with deep lesions which can involve the entire thickness of the diaphragm. In these cases, treatment is more difficult with possible incomplete pain relief and a considerable possibility of recurrence. In this subset, abdominal surgery is recommended. Surgical treatment must be individualized on the basis of the patient's age, fertility desires, type and location of disease and symptoms. We report the surgical treatment of a patient with synchronous pericardial, pleural and diaphragmatic endometriosis associated with pelvic peritoneal and bowel involvement. A review of the literature regarding pericardial and diaphragmatic endometriosis focusing on anatomical and surgical aspects of its management is undertaken.

  16. Human related mortality of birds in the United States

    USGS Publications Warehouse

    Banks, R.C.

    1979-01-01

    Modern man serves as both a direct and an indirect cause of the death of birds. In the early 1970's, human activity was responsible for the death of approximately 196 million birds per year, or about 1.9% of the wild birds of the continental United States that died each year. Hunting was the largest direct mortality factor and accounted for about 61% of human related bird deaths. Control or prevention of avian depredations took about 1% of the total, and all research and propagation about 0.5%. Collision with man-made objects was the greatest indirect human cause of avian deaths. accounting for about 32% of the human related deaths. Pollution and poisoning caused the death of about 2% of the total. A relatively few species account for most of this mortality but continue to maintain large, harvestable populations, suggesting that the numbers of most bird species are essentially unaffected by the human activities discussed. Other activities of man that do not necessarily result in the death of birds but rather reduce reproductive potential are more likely to have long-term effects on avian populations.

  17. Neurolinguistic Relativity: How Language Flexes Human Perception and Cognition

    PubMed Central

    2016-01-01

    The time has come, perhaps, to go beyond merely acknowledging that language is a core manifestation of the workings of the human mind and that it relates interactively to all aspects of thinking. The issue, thus, is not to decide whether language and human thought may be ineluctably linked (they just are), but rather to determine what the characteristics of this relationship may be and to understand how language influences—and may be influenced by—nonverbal information processing. In an attempt to demystify linguistic relativity, I review neurolinguistic studies from our research group showing a link between linguistic distinctions and perceptual or conceptual processing. On the basis of empirical evidence showing effects of terminology on perception, language‐idiosyncratic relationships in semantic memory, grammatical skewing of event conceptualization, and unconscious modulation of executive functioning by verbal input, I advocate a neurofunctional approach through which we can systematically explore how languages shape human thought. PMID:27642191

  18. Neurolinguistic Relativity: How Language Flexes Human Perception and Cognition.

    PubMed

    Thierry, Guillaume

    2016-09-01

    The time has come, perhaps, to go beyond merely acknowledging that language is a core manifestation of the workings of the human mind and that it relates interactively to all aspects of thinking. The issue, thus, is not to decide whether language and human thought may be ineluctably linked (they just are), but rather to determine what the characteristics of this relationship may be and to understand how language influences-and may be influenced by-nonverbal information processing. In an attempt to demystify linguistic relativity, I review neurolinguistic studies from our research group showing a link between linguistic distinctions and perceptual or conceptual processing. On the basis of empirical evidence showing effects of terminology on perception, language-idiosyncratic relationships in semantic memory, grammatical skewing of event conceptualization, and unconscious modulation of executive functioning by verbal input, I advocate a neurofunctional approach through which we can systematically explore how languages shape human thought.

  19. Expression of focal adhesion kinase in endometrial stromal cells of women with endometriosis was adjusted by ovarian steroid hormones.

    PubMed

    Mu, Lin; Ma, Yan-Yan

    2015-01-01

    The aim of our study is to investigate the effects of ovarian steroid hormones on focal adhesion kinase (FAK) expression in ESCs and whether there is alteration in women with endometriosis. FAK expression was assessed by western blotting analysis. Elevated expression of FAK was seen in the cultured ESCs treated with estrogen (P < 0.05). Expression of FAK protein was not changed in ESCs after treated by progesterone or treated by estrogen and progesterone. The level of up-regulation by estrogen in endometriosis is significantly higher than that from women without endometriosis (P < 0.05). FAK expression in endometrial stromal cells from endometriosis was more sensitive to estrogen, which might contribute to the pathogenesis and progress of endometriosis.

  20. Human Relations Laboratory for Junior High School Personnel.

    ERIC Educational Resources Information Center

    Israel, Joseph, A.; Savitsky, Albert M.

    A human relations laboratory for junior high school personnel was conducted as an in-service offering by two counselors. The purpose of the laboratory was to develop in the participants an appreciation of, and a capacity to perform, three primary learning tasks: (1) generation of valid and useful information; (2) organization of choices emanating…

  1. LABORATORY TRAINING IN HUMAN RELATIONS AND ORGANIZATIONAL BEHAVIOR.

    ERIC Educational Resources Information Center

    HARRISON, ROGER; OSHRY, BARRY

    A SERIES OF STUDIES WERE MADE ON THE EFFECTS OF LABORATORY TRAINING IN HUMAN RELATIONS ON THE ORGANIZATIONAL BEHAVIOR OF "MIDDLE" MANAGERS. THROUGH REPEATED FACTOR ANALYSIS, THE ORGANIZATIONAL BEHAVIOR DESCRIBER SURVEY (OBDS) WAS DEVELOPED BY WHICH A MANAGER AND HIS ASSOCIATES COULD DESCRIBE HIS BEHAVIOR. THE OBDS PERMITTED RATINGS ON…

  2. Human Relation Skills in Counseling. A Higher Education Training Monograph.

    ERIC Educational Resources Information Center

    Brown, Robert W.

    The purpose of this training module is to assist participants in acquiring high-level basic counseling skills. Specifically, trainees will master those skills crucial to the four Carkhuff stages of basic helping. The ultimate purpose is to help counselors involved in Manpower Programs upgrade their interpersonal human relations/basic counseling…

  3. Analysis of Human Relations Problem Situations: The Group Process Approach.

    ERIC Educational Resources Information Center

    Whitmore, Paul G.

    Human relations problem situations for Army senior non-commissioned officers (NCOs) were identified and analyzed using group problem solving methods. Then, using an analysis summary prepared for each case study problem situation as the basis, candidate performance exercises were developed. (These exercises specify terminal performance objectives…

  4. Human Relations: The Cornerstone of a Roeper Education

    ERIC Educational Resources Information Center

    Lutz, Lori A.; Nichols, Susannah

    2016-01-01

    This article traces the evolution of a moral philosophy curriculum originally taught by George A. Roeper in the earliest years of The Roeper School. The first author, a student at The Roeper School in the 1960s and 1970s, describes the impact of the class George Roeper called "Human Relations" on her life. Returning to the School as a…

  5. Annotated Bibliography on Human Relations--Teachers and Administrators.

    ERIC Educational Resources Information Center

    1987

    This annotated bibliography is a listing of 286 papers and journal articles on human relations in public education published between 1982 and 1986. Nearly 50 entries concern the principal's role as manager and instructional leader. Another 50 address teacher supervision and evaluation, while 30 others treat teacher burnout, stress, morale, and…

  6. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

    PubMed

    Burney, Richard O; Talbi, Said; Hamilton, Amy E; Vo, Kim Chi; Nyegaard, Mette; Nezhat, Camran R; Lessey, Bruce A; Giudice, Linda C

    2007-08-01

    The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

  7. The Surgical Treatment of Severe Endometriosis Positively Affects the Chance of Natural or Assisted Pregnancy Postoperatively

    PubMed Central

    Nesbitt-Hawes, Erin M.; Campbell, Neil; Maley, Peta E.; Won, Haryun; Hooshmand, Dona; Henry, Amanda; Ledger, William; Abbott, Jason A.

    2015-01-01

    Objective. To report reproductive outcomes following laparoscopic surgical excision of histologically confirmed r-ASRM stage III-IV endometriosis. Study Design. A retrospective cohort study was performed at the Royal Hospital for Women, a university teaching hospital, Sydney, Australia. Women who had fertility-preserving laparoscopic excision of stage III-IV endometriosis from 1997 to 2009 were contacted regarding reproductive outcomes. Results. In the study period, 355 women underwent surgery for stage III-IV endometriosis. Follow-up data are available for 253/355 (71%) women. Postoperatively, 142/253 (56%) women attempted to conceive with a conception rate of 104/142 (73%). Confidence intervals for pregnancy for women who were attempting conception (including the nonresponders) range from 104/262 (40%) to 224/262 (85%). Median time to conception was 12 months. No positive prognostic factors for pregnancy were identified on regression analyses. Conclusions. These data provide information to women with suspected severe disease preoperatively concerning their likely postoperative fertility outcomes. Ours is a population with severe endometriosis, rather than an infertile population with endometriosis, so caution needs to be applied when applying these data to women with fertility issues alone. PMID:26247022

  8. Dyspareunia and quality of sex life after surgical excision of endometriosis: a systematic review.

    PubMed

    Fritzer, N; Tammaa, A; Salzer, H; Hudelist, G

    2014-02-01

    Dyspareunia, a common symptom of endometriosis, severely affects quality of sex life in affected women. The objective of the present work was to review the effect of surgical resection of endometriosis on pain intensity and quality of sex life. MEDLINE and EMBASE databases were searched for papers investigating the outcome after surgical endometriosis resection on dyspareunia and quality of sex life measured via VAS/NAS respectively via standardised measuring instruments. Data did not permit a meaningful meta-analysis. Out of 64 papers, three studies fulfilled the predefined inclusion criteria involving 128 patients with endometriosis and dyspareunia preoperatively. All included studies showed a significant postoperative reduction (p<0.05) of dyspareunia after a follow-up period of 12 up to 60 months. Sex life also improved significantly (p<0.05), and predominantly evaluated parameters like quality of life and mental health. Intra- and postoperative complications were described in two out of three studies. Surgical excision of deep infiltrating endometriosis is feasible and improves dyspareunia and quality of sex life significantly.

  9. Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis

    PubMed Central

    Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Aradottir, Kristrun; Feenstra, Bjarke; Sigurdsson, Asgeir; Stefansdottir, Lilja; Kristinsdottir, Anna M.; Zink, Florian; Halldorsson, Gisli H.; Munk Nielsen, Nete; Geller, Frank; Melbye, Mads; Gudbjartsson, Daniel F.; Geirsson, Reynir T.; Thorsteinsdottir, Unnur; Stefansson, Kari

    2016-01-01

    We conducted a genome-wide association scan (GWAS) of endometriosis using 25.5 million sequence variants detected through whole-genome sequencing (WGS) of 8,453 Icelanders and imputed into 1,840 cases and 129,016 control women, followed by testing of associated variants in Danish samples. Here we report the discovery of a new endometriosis susceptibility locus on 4q12 (rs17773813[G], OR=1.28; P=3.8 × 10−11), upstream of KDR encoding vascular endothelial growth factor receptor 2 (VEGFR2). The variant correlates with disease severity (P=0.0046) when moderate/severe endometriosis cases are tested against minimal/mild cases. We further report association of rs519664[T] in TTC39B on 9p22 with endometriosis (P=4.8 × 10−10; OR=1.29). The involvement of KDR in endometriosis risk highlights the importance of the VEGF pathway in the pathogenesis of the disease. PMID:27453397

  10. Luteinized unruptured follicle syndrome in mild endometriosis. Assessment with biochemical parameters.

    PubMed

    Holtz, G; Williamson, H O; Mathur, R S; Landgrebe, S C; Moore, E E

    1985-09-01

    Failure to extrude an ovum, with subsequent luteinization of the unruptured follicle (LUF), has been proposed as a cause of infertility in women with mild endometriosis. To assess the incidence of this process we performed laparoscopies in the early luteal phase on 16 women with mild endometriosis and 8 control subjects. Peritoneal fluid was aspirated and a plasma sample obtained concurrently. Estradiol (E2) and progesterone (P) concentrations were determined. A review of the literature suggested that the following hormonal criteria correlated with follicular rupture: fluid E2 greater than or equal to 500 pg/ml, E2 fluid/plasma ratio greater than or equal to 3.1, fluid P greater than or equal to 3,000 ng/dl and P fluid/plasma ratio greater than or equal to 5:1. All control subjects met at least one E2 and one P criterion: 75% met all. In contrast, less than one-third with mild endometriosis met all, and three (19%) met none. Five met only E2 criteria. These findings suggest that LUF occurs occasionally in association with mild endometriosis. Additionally, ovarian steroidogenesis, particularly P secretion, was impaired frequently in the absence of LUF in women with endometriosis.

  11. Patients’ and physicians’ descriptions of occurrence and diagnosis of endometriosis: a qualitative study from Iran

    PubMed Central

    2014-01-01

    Background The prevalence of endometriosis is considerable but its diagnosis is a dilemma. The aim of this study was to explore the perception and experiences of endometriosis patients and physicians about occurrence and diagnosis of endometriosis. Methods A qualitative research using content analysis was used to obtain data from purposely selected endometriosis patients (12 participants) and gynecologists (6 participants) from January to September 2013 in Tehran. Data were coded and analyzed using a thematic approach. Results Seven themes emerged: 1) pain localization, 2) Severity of pain and struggle for pain relief, 3) Feeling inability to play the role of femininity, 4) Reducing physical health, 5) Disruption of social life, 6) Looking for a reliable diagnostic indicator, 7) Uncertainty of physical examination. The results highlighted that patients with the disease can experience different feelings that interfere with their wellbeing and their lives, and sometimes could be disabling. Conclusion Patients and physicians are looking for a certain, noninvasive and inexpensive diagnostic method. This study helps to promote clinical diagnostic view and knowledge development about description of endometriosis diagnosis to decrease diagnostic delay and mismanagement. PMID:25174639

  12. Association study of Glutathione S-Transferase polymorphisms and risk of endometriosis in an Iranian population

    PubMed Central

    Hassani, Mina; Saliminejad, Kioomars; Heidarizadeh, Masood; Kamali, Koorosh; Memariani, Toktam; Khorram Khorshid, Hamid Reza

    2016-01-01

    Background: Endometriosis influenced by both genetic and environmental factors. Associations of glutathione S-transferases (GSTs) genes polymorphisms in endometriosis have been investigated by various researchers; however, the results are not consistent. Objective: We examined the associations of GSTM1 and GSTT1 null genotypes and GSTP1 313 A/G polymorphisms with endometriosis in an Iranian population. Materials and Methods: In this case-control study, 151 women with diagnosis of endometriosis and 156 normal healthy women as control group were included. The genotyping was determined using multiplex PCR and PCR- RFLP methods. Results: The GSTM1 null genotype was significantly higher (p=0.027) in the cases (7.3%) than the control group (1.3%). There was no significant difference between the frequency of GSTT1 genotypes between the cases and controls. The GSTP1 313 AG genotype was significantly lower (p=0.048) in the case (33.1%) than the control group (44.4%). Conclusion: Our results showed that GSTM1 and GSTP1 polymorphisms may be associated with susceptibility of endometriosis in Iranian women. PMID:27351025

  13. Putting the pieces together: endometriosis blogs, cognitive authority, and collaborative information behavior*

    PubMed Central

    Neal, Diane M; McKenzie, Pamela J

    2011-01-01

    Objective: A discourse analysis was conducted of peer-written blogs about the chronic illness endometriosis to understand how bloggers present information sources and make cases for and against the authority of those sources. Methods: Eleven blogs that were authored by endometriosis patients and focused exclusively or primarily on the authors' experiences with endometriosis were selected. After selecting segments in which the bloggers invoked forms of knowledge and sources of evidence, the text was discursively analyzed to reveal how bloggers establish and dispute the authority of the sources they invoke. Results: When discussing and refuting authority, the bloggers invoked many sources of evidence, including experiential, peer-provided, biomedical, and intuitive ones. Additionally, they made and disputed claims of cognitive authority via two interpretive repertoires: a concern about the role and interests of the pharmaceutical industry and an understanding of endometriosis as extremely idiosyncratic. Affective authority of information sources was also identified, which presented as social context, situational similarity, or aesthetic or spiritual factors. Conclusions: Endometriosis patients may find informational value in blogs, especially for affective support and epistemic experience. Traditional notions of authority might need to be revised for the online environment. Guidelines for evaluating the authority of consumer health information, informed by established readers' advisory practices, are suggested. PMID:21464850

  14. The Effects and Possible Mechanisms of Puerarin to Treat Endometriosis Model Rats

    PubMed Central

    Zhao, Li; Zhang, Danying; Zhai, Dongxia; Shen, Wei; Bai, Lingling; Liu, Yiqun; Cai, Zailong; Li, Ji; Yu, Chaoqin

    2015-01-01

    Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17β-hydroxysteroid-2 (17β-hsd-2) and downregulating the expression of 17β-hydroxysteroid-1 (17β-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERβ and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic. PMID:25815028

  15. Management of patients with chronic pelvic pain associated with endometriosis refractory to conventional treatment.

    PubMed

    Martínez, Blanca; Canser, Enrique; Gredilla, Elena; Alonso, Eduardo; Gilsanz, Fernando

    2013-01-01

    The literature contains numerous studies on the diagnosis, pathogenesis, atypical locations, and clinical (hormonal) and surgical management of the disorder. However, no information is available on the management of endometriosis involving pain refractory to the usual treatment from the perspective of a pain unit. Our hospital has a pain unit specifically dedicated to pain in gynecology and obstetrics. The unit has been functioning since December 2005, and 52% of the attended patients have CPP of different origins. Endometriosis is present in 48% of all patients with CPP and is the most prevalent pathology in our practice. It moreover poses an important challenge in view of its enormous complexity. A descriptive study was made of the management of 44 patients with endometriosis refractory to therapy, evaluated and treated over a period of 3 years in the Pain Unit of the Maternity Center of La Paz University Hospital (Madrid, Spain).

  16. Stress management affects outcomes in the pathophysiology of an endometriosis model.

    PubMed

    Appleyard, Caroline B; Cruz, Myrella L; Hernández, Siomara; Thompson, Kenira J; Bayona, Manuel; Flores, Idhaliz

    2015-04-01

    We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim stress protocol. Corticosterone levels and fecal pellet numbers were measured as an indicator of stress. Uncontrollable stress increased the number and size of the endometriotic cysts. Rats receiving uncontrollable stress had higher anxiety than those exposed to controllable stress or no stress and higher corticosterone levels. Uncontrollable stressed rats had more colonic damage and uterine cell infiltration compared to no stress, while controllable stress rats showed less of an effect. Uncontrollable stress also increased both colonic and uterine motility. In summary, the level of stress controllability appears to modulate the behavior and pathophysiology of endometriosis and offers evidence for evaluating therapeutic interventions.

  17. Long-lasting analgesic effect of transcranial direct current stimulation in treatment of chronic endometriosis pain.

    PubMed

    Rostami, Reza; Badran, Bashar W; Kazemi, Reza; Habibnezhad, Mohammad; George, Mark S

    2015-12-01

    Approximately 10-20% of women of reproductive age suffer from endometriosis, with 70-90% of these women reporting chronic pain symptoms that persist during their menstrual cycle. We are presenting a case in which a novel form of noninvasive brain stimulation called transcranial direct current stimulation was used as an intervention in a 32-year-old woman with persistent, chronic pain symptoms caused by endometriosis for 20 years. Ten daily, 20-min sessions of 2-mA anodal transcranial direct current stimulation were applied over the left primary motor cortex. Acutely, visual analog scale pain symptoms were reduced by 60%. There were also significant decreases in modules of the Endometriosis Health Profile. At the 4-month follow-up, the patient still expressed an overall decrease in pain symptoms of 30%.

  18. Activin A Stimulates Aromatase via the ALK4-Smad Pathway in Endometriosis

    PubMed Central

    Zheng, Juan; Qu, Juan; Lu, Pinhong; Mao, Yundong; Qi, Xiaochen; Ji, Hui; Liu, Jiayin

    2016-01-01

    Endometriosis is an estrogen-dependent disease. We previously found that the expression of Activin A was upregulated in the peritoneal fluid of patients with endometriosis. The results of the present study indicated that Activin A induced estradiol secretion and P450arom expression in endometrial stromal cells (ESCs) derived from endometriosis patients. The mechanism of estrogenic synthesis was regulated by the Activin-Smad pathway in endometrial lesions. The data showed that the effect of Activin A on ESCs was partially abrogated by pretreatment with an inhibitor of ALK4 (the type I receptor, ActRIB) and Smad4-siRNA. Cumulatively, these data suggest that Activin A promotes the secretion of estradiol from ESCs by increasing the expression of P450arom via the ALK4-Smad pathway. These findings indicate the ALK4-Smad pathway may promote ectopic lesion survival and development. PMID:27833918

  19. Human polyomavirus related to African green monkey lymphotropic polyomavirus.

    PubMed

    Sauvage, Virginie; Foulongne, Vincent; Cheval, Justine; Ar Gouilh, Meriadeg; Pariente, Kevin; Dereure, Olivier; Manuguerra, Jean Claude; Richardson, Jennifer; Lecuit, Marc; Burguière, Ana; Caro, Valérie; Eloit, Marc

    2011-08-01

    While studying the virome of the skin surface of a patient with a Merkel cell carcinoma (MCC) by using unbiased, high-throughput sequencing, we identified a human polyomavirus nearly identical to human polyomavirus 9, a virus recently reported in blood and urine of renal transplantion patients and closely related to the African green monkey lymphotropic polyomavirus. Specific PCR analysis further identified this virus in 2/8 patients with MCC but in only 1/111 controls without MCC. This virus was shed for ≥20 months by the MCC index patient and was on the skin of the spouse of the index patient. These results provide information on the viral ecology of human skin and raise new questions regarding the pathology of virus-associated skin disorders.

  20. Prospective study concerning 71 cases of caesarean scar endometriosis (CSE).

    PubMed

    Pas, Katarzyna; Joanna, Skręt-Magierło; Renata, Raś; Skręt, Andrzej; Barnaś, Edyta

    2017-04-11

    A prospective study was undertaken involving 71 patients with caesarean scar endometriosis (CSE) between the years 2007 and 2013. A prospective study enabled us to find out: mean age of patients with CSE; 34.0 years (range 22.0-48.0), time between CS and diagnosis of CSE; 12.0 months (range 19.0-39.0), duration between symptoms and surgery; 24.0 months (range 1.0-204.0), mean operation time; 40.0 min. (range 15.0-160.0), and mean lesion size; 54.4 ± 42.3 mm(3). In three patients (4.2%) a large deficit in the abdominal wall was closed by means of polypropylene mesh. One of them conceived a year later. Surgical excision is the only effective treatment in patients with CSE. Wide local excision with clear margins is the key to prevent recurrence. Repair of large post-excisional deficits with mesh may also be offered to woman planning their next pregnancy. Impact statement • What is already known on this subject? Endometriosis in the scar may occur after various abdominal surgeries, more frequently after caesarean sections. The excision of large nodules is connected with suboptimal cosmetic outcomes and the possibility of recurrence. • What the results of this study add? In this study including 71 patients with CSE, wide excision with electrocoagulatory was associated with a single recurrence in 12-month follow-up. In three patients (4.2%) large deficits in the abdominal wall were closed with the use of polypropylene mesh. One of them conceived a year later and had a successful pregnancy. • What the implications are of these findings for clinical practice and/or futher research? Surgical excision is the only effective treatment in patients with CSE. Wide local excision with clear margins is the key to preventing recurrence. Repair of large post excisional deficit with mesh may be offered also to woman planning pregnancy.

  1. Valproic acid and progestin inhibit lesion growth and reduce hyperalgesia in experimentally induced endometriosis in rats.

    PubMed

    Liu, Maohua; Liu, Xishi; Zhang, Yuqiu; Guo, Sun-Wei

    2012-04-01

    Accumulating evidence suggests that endometriosis is an epigenetic disease. This study was designed to evaluate the effect of valproic acid (VPA) and progesterone (P4) in a rat model of endometriosis on serum tumor necrosis factor-α (TNF-α) levels, hot plate and tail-flick latencies, lesion size, and body weight. We used 77 adult female rats, and endometriosis was induced by autotransplanting pieces of uterus (ENDO) or fat (SHAM) to the pelvic cavity. The BLANK group received no surgery. After 2 weeks, the ENDO group was further divided, randomly, into 5 groups, receiving, respectively, treatment with low- and high-dose VPA, P4 alone, VPA + P4, and no treatment. The SHAM rats received no treatment. The BLANK rats were further divided into 2 groups, one received VPA treatment and the other, no treatment. After 4 weeks, all rats were sacrificed. Response latency in hot plate and tail-flick tests, body weight, and serum TNF-α levels were measured before the surgery, before and after the treatment, along with lesion size. We found that induced endometriosis reduced response latency. ENDO rats receiving VPA and/or P4 treatment had significantly reduced lesion size as compared with untreated ones, and had significantly improved response to noxious thermal stimuli. They also had significantly increased weight gain. Serum TNF-α levels increased following surgery but eventually decreased regardless of treatment or not. In conclusion, VPA is well tolerated. Treatment with VPA significantly reduces lesion growth and improves sensitivity to nocifensive stimuli. The improvement is specific to endometriosis-induced hyperalgesia. Thus, histone deacetylase inhibitors may be a promising therapeutics for treating endometriosis.

  2. Shift work, hCLOCK T3111C polymorphism, and endometriosis risk

    PubMed Central

    Marino, Jennifer L.; Holt, Victoria L.; Chen, Chu; Davis, Scott

    2010-01-01

    Background Endometriosis, a dysplastic disease affecting approximately 5-10% of U.S. reproductive-age women, has been linked in epidemiologic studies to exposures indicating high circulating estrogen levels. One such exposure may be night shift work, which has been associated with menstrual disruption and increased risk of two other estrogen-influenced diseases, breast cancer and adverse coronary events. Methods In this population-based case-control study, 235 health maintenance organization enrollees aged 18-49 first diagnosed with surgically-confirmed endometriotic disease between 4/1/1996 and 3/31/2001 were frequency-matched on age with 545 randomly selected female GH enrollees without history of endometriosis. Participants were asked about night shift work in all paid fulltime or part-time jobs worked from age 18 to the reference date. Genotypes for T3111C hClock were determined for a subset of 218 cases and 456 controls. Results Any night shift work was associated with a 50% increase in risk of endometriosis (odds ratio (OR) 1.48, 95% confidence interval (CI) 0.96, 2.29), and working more than half of shifts on a job at night was associated with a nearly doubled disease risk (OR 1.98, 95% CI 1.01, 3.85.) Changing sleep patterns on days off was associated with further increases in disease risk. T3111C hClock polymorphism was unrelated to endometriosis status and did not modify the effect of shift work on endometriosis. Conclusions These findings suggest that some aspect of night shift work may influence the development of endometriosis. PMID:18379422

  3. [Relationship among anthropometric and gluco-metabolic parameters, bone mineral density and endometriosis].

    PubMed

    Nava-González, Edna J; de la Garza-Casas, Yolanda E; Salazar-Montalvo, Raúl G; Gallegos-Cabriales, Esther C

    2013-01-01

    Introducción: las mujeres con endometriosis cursan con una densidad mineral ósea (DMO) disminuida. Varios estudios han demostrado que la acumulación del tejido adiposo afecta profundamente la DMO. También se ha documentado que un exceso de grasa corporal se asocia con el desarrollo de endometriosis. Nuestro objetivo fue analizar la relación entre la DMO, la masa grasa corporal y el eje insulina-glucosa en mujeres con endometriosis. Métodos: treinta mujeres con diagnóstico laparoscópico de endometriosis aceptaron participar en este estudio. Se les efectuó antropometría y densitometría dual de rayos X para determinar su índice de masa corporal, su composición corporal y su DMO. Se les determinaron mediciones de insulina y glucosa en ayuno y posprandiales. Resultados: para el análisis de los resultados, se utilizaron metodologías de estadística descriptiva y prueba de Pearson. Existió un patrón entre cada fenotipo caracterizado y el T-score de la DMO en nuestras participantes con endometriosis.Conclusiones: la importancia de encontrar correlaciones clínico-observacionales entre enfermedades prevalentes que afectan la composición corporal en la población femenina (endometriosis, osteoporosis, diabetes y obesidad) podría dar lugar a hipótesis sobre una génesis causal común entre estas condiciones patológicas.

  4. The importance of endometrial nerve fibers and macrophage cell count in the diagnosis of endometriosis

    PubMed Central

    Cetin, Cihan; Serdaroglu, Hasan; Tuzlali, Sitki

    2013-01-01

    Background: Endometriosis is a disease that is hard to diagnose without the gold standard method, laparoscopy. An easier diagnostic method is needed. Objective: The aim of the study is to determine whether the number of macrophage cells in the endometrium and/or the detection of nerve fibers can be used in the diagnosis of endometriosis. Materials and Methods: Endometrial sampling was done to 31 patients prior to laparoscopy (L/S) or laparotomy (L/T) at Istanbul University Istanbul School of Medicine Hospital between January 2010 February 2011. Also 34 patients who were retrospectively chosen from their files were added to the study. 5 patients were excluded from the study. Totally, 31 patients were placed in the endometriosis and 29 patients in the control group. Endometrial samples were evaluated immunohistochemically with the markers protein gene product 9.5 (PGP 9.5) and neurofilament (NF) for nerve fibers and CD68 for macrophages. Results: None of the samples were stained with PGP 9.5 and NF. As for CD68+cells, no statistically significant difference was observed between groups (endometriosis: 216.10±104.41; control: 175.93±43.05, p=0.06). Results were also evaluated in the subgroups of menstruel phases and disease stages. Only in the proliferative phase there was a significant increase in the endometriosis group (p=0.03). No significant difference was observed between the stages. Conclusion: The detection of nerve fibers in the eutopic endometrium with the markers of PGP 9.5 and NF is not found to be helpful in the diagnosis of endometriosis. Macrophage cells may be helpful in the diagnosis only in the proliferative phase. PMID:24639773

  5. Correlation of CA-125 serum level and clinico-pathological characteristic of patients with endometriosis

    PubMed Central

    Karimi-Zarchi, Mojgan; Dehshiri-Zadeh, Najmeh; Sekhavat, Leili; Nosouhi, Fahime

    2016-01-01

    Background: Cancer antigen 125 (CA-125) is a glycoprotein biomarker that is used in women with pelvic masses such as endometriosis and maybe is useful in practice of patients suspicious to endometriosis. Objective: The aim of this study was to evaluate the association between preoperative serum CA-125 levels and clinic pathological characteristic in women with endometriosis, and find out the best serum CA-125 levels cut-off in pre and post menopause women. Materials and Methods: Serum CA-125 levels in 87 women aged 21-54 years suspected to endometriosis with pelvic pain, dysmenorrhea, or dyspareunia were measured preoperatively. Also the association between clinic pathological characteristic and serum CA-125 level were analyzed. Results: The mean age of women was 32.22±6.91. The mean serum CA-125 level was 49.93±4.30 U/mL. There was a significant correlation between the endometriosis stage, lesion size, adhesion score and preoperative CA-125 plasma concentration. However, we did not found significant differences in age, marital status, patient’s complaints, and pelvic pain associated to Ca125 serum level. The suggested preoperative serum cut-off levels in premenopausal and postmenopausal patients were 37 U/ml and 35 U/ml, respectively. Conclusion: According to the results, preoperative serum CA-125 is an important predictor for patients with endometriosis and it should be taken into consideration when surgical management is suspected, especially if stage of disease, lesion size and adhesion score are undertaken. PMID:28008424

  6. Rapidly quantifying the relative distention of a human bladder

    NASA Technical Reports Server (NTRS)

    Companion, John A. (Inventor); Heyman, Joseph S. (Inventor); Mineo, Beth A. (Inventor); Cavalier, Albert R. (Inventor); Blalock, Travis N. (Inventor)

    1991-01-01

    A device and method was developed to rapidly quantify the relative distention of the bladder of a human subject. An ultrasonic transducer is positioned on the human subject near the bladder. A microprocessor controlled pulser excites the transducer by sending an acoustic wave into the human subject. This wave interacts with the bladder walls and is reflected back to the ultrasonic transducer where it is received, amplified, and processed by the receiver. The resulting signal is digitized by an analog to digital converter, controlled by the microprocessor again, and is stored in data memory. The software in the microprocessor determines the relative distention of the bladder as a function of the propagated ultrasonic energy. Based on programmed scientific measurements and the human subject's past history as contained in program memory, the microprocessor sends out a signal to turn on any or all of the available alarms. The alarm system includes and audible alarm, the visible alarm, the tactile alarm, and the remote wireless alarm.

  7. A family of human cdc2-related protein kinases.

    PubMed Central

    Meyerson, M; Enders, G H; Wu, C L; Su, L K; Gorka, C; Nelson, C; Harlow, E; Tsai, L H

    1992-01-01

    The p34cdc2 protein kinase is known to regulate important transitions in the eukaryotic cell cycle. We have identified 10 human protein kinases based on their structural relation to p34cdc2. Seven of these kinases are novel and the products of five share greater than 50% amino acid sequence identity with p34cdc2. The seven novel genes are broadly expressed in human cell lines and tissues with each displaying some cell type or tissue specificity. The cdk3 gene, like cdc2 and cdk2, can complement cdc28 mutants of Saccharomyces cerevisiae, suggesting that all three of these protein kinases can play roles in the regulation of the mammalian cell cycle. The identification of a large family of cdc2-related kinases opens the possibility of combinatorial regulation of the cell cycle together with the emerging large family of cyclins. Images PMID:1639063

  8. Consumption of human milk oligosaccharides by gut-related microbes.

    PubMed

    Marcobal, Angela; Barboza, Mariana; Froehlich, John W; Block, David E; German, J Bruce; Lebrilla, Carlito B; Mills, David A

    2010-05-12

    Human milk contains large amounts of complex oligosaccharides that putatively modulate the intestinal microbiota of breast-fed infants by acting as decoy binding sites for pathogens and as prebiotics for enrichment of beneficial bacteria. Several bifidobacterial species have been shown to grow well on human milk oligosaccharides. However, few data exist on other bacterial species. This work examined 16 bacterial strains belonging to 10 different genera for growth on human milk oligosaccharides. For this propose, a chemically defined medium, ZMB1, was used, which allows vigorous growth of a number of gut-related microorganisms in a fashion similar to complex media. Interestingly, Bifidobacterium longum subsp. infantis, Bacteroides fragilis , and Bacteroides vulgatus strains were able to metabolize milk oligosaccharides with high efficiency, whereas Enterococcus , Streptococcus , Veillonella , Eubacterium , Clostridium , and Escherichia coli strains grew less well or not at all. Mass spectrometry-based glycoprofiling of the oligosaccharide consumption behavior revealed a specific preference for fucosylated oligosaccharides by Bi. longum subsp. infantis and Ba. vulgatus. This work expands the current knowledge of human milk oligosaccharide consumption by gut microbes, revealing bacteroides as avid consumers of this substrate. These results provide insight on how human milk oligosaccharides shape the infant intestinal microbiota.

  9. Consumption of Human Milk Oligosaccharides by Gut-related Microbes

    PubMed Central

    Marcobal, Angela; Barboza, Mariana; Froehlich, John W.; Block, David E.; German, J. Bruce; Lebrilla, Carlito B.; Mills, David A.

    2010-01-01

    Human milk contains large amounts of complex oligosaccharides that putatively modulate the intestinal microbiota of breast-fed infants by acting as decoy binding sites for pathogens and as prebiotics for enrichment of beneficial bacteria. Several bifidobacterial species have been shown to grow well on human milk oligosaccharides. However, little data exists on other bacterial species. In this work we examined 16 bacterial strains belonging to 10 different genera for growth on human milk oligosaccharides. For this propose, we used a chemically-defined medium, ZMB1, which allows vigorous growth of a number gut–related microorganisms in a fashion similar to complex media. Interestingly, Bifidobacterium longum subsp. infantis, Bacteroides fragilis and Bacteroides vulgatus strains were able to metabolize milk oligosaccharides with high efficiency, while Enterococcus, Streptococcus, Veillonella, Eubacterium, Clostridium, and Escherichia coli strains grew less well or not at all. Mass spectrometry-based glycoprofiling of the oligosaccharide consumption behavior revealed a specific preference for fucosylated oligosaccharides by Bifidobacterium longum subsp. infantis and Bacteroides vulgatus. This work expands the current knowledge of human milk oligosaccharides consumption by gut microbes, revealing bacteroides as avid consumer of this substrate. These results provide insight on how human milk oligosaccharides shape the infant intestinal microbiota. PMID:20394371

  10. Learning multiple relative attributes with humans in the loop.

    PubMed

    Qian, Buyue; Wang, Xiang; Cao, Nan; Jiang, Yu-Gang; Davidson, Ian

    2014-12-01

    Semantic attributes have been recognized as a more spontaneous manner to describe and annotate image content. It is widely accepted that image annotation using semantic attributes is a significant improvement to the traditional binary or multiclass annotation due to its naturally continuous and relative properties. Though useful, existing approaches rely on an abundant supervision and high-quality training data, which limit their applicability. Two standard methods to overcome small amounts of guidance and low-quality training data are transfer and active learning. In the context of relative attributes, this would entail learning multiple relative attributes simultaneously and actively querying a human for additional information. This paper addresses the two main limitations in existing work: 1) it actively adds humans to the learning loop so that minimal additional guidance can be given and 2) it learns multiple relative attributes simultaneously and thereby leverages dependence amongst them. In this paper, we formulate a joint active learning to rank framework with pairwise supervision to achieve these two aims, which also has other benefits such as the ability to be kernelized. The proposed framework optimizes over a set of ranking functions (measuring the strength of the presence of attributes) simultaneously and dependently on each other. The proposed pairwise queries take the form of which one of these two pictures is more natural? These queries can be easily answered by humans. Extensive empirical study on real image data sets shows that our proposed method, compared with several state-of-the-art methods, achieves superior retrieval performance while requires significantly less human inputs.

  11. Persistent Mullerian Duct Syndrome with Ovarian Endometriosis-A Rare Case Report

    PubMed Central

    Hippargi, Surekha B.; Mestri, Namrata B.; Mehrotra, Nikhil M.

    2016-01-01

    Persistent Mullerian Duct Syndrome (PMDS) is a rare form of internal male pseudohermaphroditism, characterised by presence of Mullerian duct derivatives in a genotypic and phenotypic male. It is caused by absence of anti- Mullerian hormone or defective functioning of its receptors. We report a case of 19-year-old cryptorchid male with history of orchideopexy who was clinically and radiologically diagnosed as left sided chylocele. A definitive diagnosis of PMDS with ovarian endometriosis was made on histopathological examination which is important for genetic counselling and to reduce complications like infertility and neoplastic transformation. We report this case of PMDS with ovary showing evidence of endometriosis for its rarity. PMID:27042476

  12. Bladder Endometriosis and Endocervicosis: Presentation of 2 Cases with Endoscopic Management and Review of Literature

    PubMed Central

    Fuentes Pastor, Javier; Ballestero Diego, Roberto; Correas Gómez, Miguel Ángel; Torres Díez, Eduardo; Fernández Flórez, Alejandro; Ballesteros Olmos, Gerardo; Gutierrez Baños, Jose Luis

    2014-01-01

    Urinary tract endometriosis and endocervicosis are an uncommon pathologic finding, with a common embryological origin. We present 2 cases of female patients with bladder mass. The first one was a finding of a nodular formation in the bladder during study of a nonviable foetus and the second was an incidental finding of a neoformation in the fundus of the bladder during the realization of an ultrasound. In both cases, we performed a surgical management with transurethral resection. Histopathological examination revealed a bladder endometrioma in the first case and endocervicosis with associated endometriosis in the second. PMID:25184072

  13. Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study

    PubMed Central

    Peterson, C. Matthew; Johnstone, Erica B.; Hammoud, Ahmad O.; Stanford, Joseph B.; Varner, Michael W.; Kennedy, Anne; Chen, Zhen; Sun, Liping; Fujimoto, Victor Y.; Hediger, Mary L.; Buck Louis, Germaine M.

    2014-01-01

    OBJECTIVE We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN In this prospective matched, exposure cohort design, 495 women aged 18–44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, populationcohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort. RESULTS The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3–4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3–4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57–3.76) and population (AOR, 7.91; 95% CI, 1.69–37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28–4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44–5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32–0.75), parity (AOR, 0.42; 95% CI, 0.28–0.64), and body mass index (AOR, 0.95; 95% CI, 0.93–0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor. CONCLUSION An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized. PMID:23454253

  14. Representation of stable social dominance relations by human infants.

    PubMed

    Mascaro, Olivier; Csibra, Gergely

    2012-05-01

    What are the origins of humans' capacity to represent social relations? We approached this question by studying human infants' understanding of social dominance as a stable relation. We presented infants with interactions between animated agents in conflict situations. Studies 1 and 2 targeted expectations of stability of social dominance. They revealed that 15-mo-olds (and, to a lesser extent, 12-mo-olds) expect an asymmetric relationship between two agents to remain stable from one conflict to another. To do so, infants need to infer that one of the agents (the dominant) will consistently prevail when her goals conflict with those of the other (the subordinate). Study 3 and 4 targeted the format of infants' representation of social dominance. In these studies, we found that 12- and 15-mo-olds did not extend their expectations of dominance to unobserved relationships, even when they could have been established by transitive inference. These results suggest that infants' expectation of stability originates from their representation of social dominance as a relationship between two agents rather than as an individual property. Infants' demonstrated understanding of social dominance reflects the cognitive underpinning of humans' capacity to represent social relations, which may be evolutionarily ancient, and may be shared with nonhuman species.

  15. The 763C>G Polymorphism of The Secretory PLA2IIa Gene Is Associated with Endometriosis in Iranian Women

    PubMed Central

    Sahmani, Mehdi; Darabi, Masoud; Darabi, Maryam; Dabaghi, Talaat; Alizadeh, Safar Ali; Najafipour, Reza

    2015-01-01

    Background Endometriosis is a chronic gynecological disease resulting from complex interactions between genetic, hormonal, environmental and oxidative stress and intrinsic inflammatory components. The aim of this study was to investigate the potential association of the 763C>G polymorphism in the secretory phospholipase A2 group IIa gene (PLA2G2A) with the risk of endometriosis in Iranian women. Materials and Methods Ninety seven patients with endometriosis along with 107 women who were negative for endometriosis after laparoscopy and laparatomy, and served as the control group, were enrolled for this cross-sectional study. Samples were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Results Multivariate analysis was used to examine the association between the risk of endometriosis and the 763C>G polymorphism of PLA2G2A. Genotype distributions of PLA2G2A were significantly different between patients and the controls (p<0.001, OR=0.22, 95% CI=0.21-0.39). Correlation analysis showed that there was a significant association between the normal homozygous genotype and susceptibility to endometriosis (p<0.001). Conclusion The present study suggests that the 763C>G polymorphism of PLA2G2A plays an important role as an independent factor in the risk of endometriosis in Iranian women. PMID:25780526

  16. Genetic polymorphisms in patients with endometriosis: an analytical study in Goiânia (Central West of Brazil).

    PubMed

    Silva, K S F; Moura, K K V O

    2016-05-25

    In healthy women, intra- and extracellular controls prevent the attachment and proliferation of ectopic endometrial cells. During endometriosis, abnormalities in these control mechanisms permit the survival of endometrial cells, their subsequent attachment to the peritoneal cavity, and disease progression. These abnormal cells cause invasion of tissues and induce an inflammatory response. Several genetic, immunological, and environmental factors contribute to this complex process. In this study we examined 6 polymorphisms for 6 different genes (p53; estrogen receptor β; progesterone receptor; GSTM1; GSTT1; CYP1A1). We obtained polymorphic genotype frequencies of all genes for 50 patients and analyzed them using the Fisher exact test or G test. Initially, we analyzed the genes in groups of 2, followed by 3. We found a significant association between polymorphisms in 6 pairs of genes (p53-ERβshowed 5.9-times higher frequency in the experimental group, p53-GSTM1 showed 2.39 times higher, 65.5% patients showed p53-CYP1A1 polymorphism, ERβ-PROGINS showed 3.0-times higher frequency, while 31.25% patients showed GSTM1- PROGINS and GSTT1-CYP1A1 polymorphism). Positive results were found in 15 situations when genes were analyzed in groups of 3; the most significant result corresponded to polymorphisms of p53, ERβand GSTM1 seen in 20%; PROGINS, ERβand GSTM1 in 18%; and p53, ERβand PROGINS in 12% patients. The results indicate that the presence of polymorphisms in more than one endometriosis-related gene is associated with onset of disease and progression. Future studies should focus on these genes to understand their inter-relationships and explore the possibility of developing new diagnostic techniques based on molecular markers.

  17. DRUMS: a human disease related unique gene mutation search engine.

    PubMed

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html.

  18. Effect of Natural Cycle Endometrial Preparation for Frozen-Thawed Embryo Transfer in Patients with Advanced Endometriosis

    PubMed Central

    Guo, Haiyan; Wang, Yun; Chen, Qiuju; Chai, Weiran; Lv, Qifeng; Kuang, Yanping

    2016-01-01

    Background The aim of this study was to investigate the effect of natural cycle (NC) endometrial preparation for frozen-thawed embryo transfer (FET) in women with advanced endometriosis. Material/Methods This retrospective study included 179 patients with stage III–IV endometriosis who underwent 233 FET cycles at a tertiary care academic reproductive medical center between March 2011 and August 2013 (group A). The control group included 258 patients with tubal factor infertility who underwent 300 FET cycles (group B). Both groups were prepared for FET using a NC protocol. Rates of implantation, clinical pregnancy, live birth, ongoing pregnancy, miscarriage, and pregnancy complication were recorded. Results The implantation rate (A: 36.0%, B: 30.4%, P=0.06), the pregnancy rate (A: 50.2%, B: 45.3%, P=0.263), and the live birth rate (A: 39.91%, B: 39.0%, P=0.428) were similar between the stage III–IV endometriosis and tubal factor infertility groups. No differences were observed in ongoing rates of pregnancy, miscarriage, and pregnancy complications, independent of endometriosis severity. No congenital birth defects were found. When high-quality embryos are transferred, pregnancy results were not affected by active endometriosis. Although severe endometriosis did not affect birth rate, higher frequencies of premature delivery (mean gestational age A: 37 weeks, B: 38.3 weeks, P=0.044) and low birth weight were observed (<2500 g A: 26.4%, B: 16.6%, P=0.047). Conclusions There was no difference in pregnancy outcomes between patients with endometriosis and those with tubal infertility. Pregnancy outcomes in patients with endometriosis were not affected by endometriosis severity. Pregnancy outcomes were not affected by active endometrial cyst. PMID:27889789

  19. Investigations Into Age-related Changes in the Human Mandible().

    PubMed

    Parr, Nicolette M; Passalacqua, Nicholas V; Skorpinski, Katie

    2017-03-02

    While changes in mandibular shape over time are not widely recognized by skeletal biologists, mandibular remodeling and associated changes in gross morphology may result from a number of causes related to mechanical stress such as antemortem tooth loss, changes in bite force, or alterations of masticatory performance. This study investigated the relationship between age-related changes and antemortem tooth loss in adult humans via dry bone measurements. This study examined 10 standard mandibular measurements as well as individual antemortem tooth loss scores using the Eichner Index from a total of 319 female and male individuals with ages ranging from 16 to 99 years. Results indicate that few mandibular measurements exhibited age-related changes, and most were affected by antemortem tooth loss.

  20. 'No one agrees except for those of us who have it': endometriosis patients as an epistemological community.

    PubMed

    Whelan, Emma

    2007-11-01

    This paper contributes to the literature on patients' claims-making work by analysing the epistemological strategies and standards used by members of an endometriosis patient community. It draws upon focus group research with members of a support group for endometriosis sufferers, and an open-ended survey of an e-mail list for women with the disease. Lynn Hankinson Nelson's (1993) concept of epistemological community is used to examine standards and practices for developing and evaluating knowledge used by women with endometriosis. Particular attention is paid to the use and centrality of the notion of experience within this community.

  1. Carotid baroreceptor-muscle sympathetic relation in humans.

    PubMed

    Rea, R F; Eckberg, D L

    1987-12-01

    The purpose of this study was to define the relation between carotid distending pressure and muscle sympathetic activity in humans. Carotid baroreceptors of nine healthy subjects were compressed or stretched for 5 s with graded neck pressure or suction (+40 to -65 mmHg), and muscle sympathetic nerve activity was recorded. The results delineate several features of human baroreflex function. First, the carotid-muscle sympathetic relation is well described by an inverse sigmoid function. Second, a linear relation exists between carotid distending pressure and sympathetic outflow over a range of approximately 25 mmHg. Third, sympathetic responses to changes of carotid pressures are asymmetric; increases of sympathetic activity during carotid compression are much greater than reductions of sympathetic activity during carotid stretch. Fourth, at rest, normal subjects operate near the threshold level for sympathetic excitation. Thus the carotid-muscle sympathetic baroreflex is poised to oppose reductions more effectively than elevations of arterial pressure, and the range of pressures over which the reflex is active is wider than thought hitherto.

  2. ERβ- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis.

    PubMed

    Monsivais, D; Dyson, M T; Yin, P; Coon, J S; Navarro, A; Feng, G; Malpani, S S; Ono, M; Ercan, C M; Wei, J J; Pavone, M E; Su, E; Bulun, S E

    2014-08-01

    In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-β (ERβ) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ERβ binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ERβ target. Estradiol potently induced RERG mRNA and protein levels in primary endometriotic stromal cells. Chromatin immunoprecipitation demonstrated E2-induced enrichment of ERβ at the RERG promoter region. PGE2 via protein kinase A phosphorylated RERG and enhanced the nuclear translocation of RERG. RERG induced the proliferation of primary endometriotic cells. Overall, we demonstrated that E2/ERβ and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation and represents a novel candidate for therapeutic intervention.

  3. ERβ- and Prostaglandin E2-Regulated Pathways Integrate Cell Proliferation via Ras-like and Estrogen-Regulated Growth Inhibitor in Endometriosis

    PubMed Central

    Monsivais, D.; Dyson, M. T.; Yin, P.; Coon, J. S.; Navarro, A.; Feng, G.; Malpani, S. S.; Ono, M.; Ercan, C. M.; Wei, J. J.; Pavone, M. E.; Su, E.

    2014-01-01

    In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-β (ERβ) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ERβ binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ERβ target. Estradiol potently induced RERG mRNA and protein levels in primary endometriotic stromal cells. Chromatin immunoprecipitation demonstrated E2-induced enrichment of ERβ at the RERG promoter region. PGE2 via protein kinase A phosphorylated RERG and enhanced the nuclear translocation of RERG. RERG induced the proliferation of primary endometriotic cells. Overall, we demonstrated that E2/ERβ and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation and represents a novel candidate for therapeutic intervention. PMID:24992181

  4. Structural studies of human glioma pathogenesis-related protein 1

    SciTech Connect

    Asojo, Oluwatoyin A.; Koski, Raymond A.; Bonafé, Nathalie

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  5. [Human social activity under conditions of relative social isolation].

    PubMed

    Prokhvatilov, A Iu

    1992-01-01

    The differences in using a "social isolation" concept in the psychological literature are presented. The term of "relative social isolation" is clarified. A relationship between human adaptation to the relative social isolation environments and the development of his social qualities and social activities is presented. The "social context", dictating motivation attitudes of a man to the isolation situation, emotional experiences, self-appraisal of activity is of crucial importance for evaluating the real environments of relative social isolations. Social activity of a personality is studied as the relations of a man with the conditions of his activity. The results of studying the dynamics of the psychic state of a man during individual and group isolation are compared. It is concluded that social activity of man and his functional state are interrelated. The particular manifestations and direction of the changes in the social activity of the subject depend on the duration of isolation and are determined first of all by social significance and meaningful and balanced work for a person as well as by the amount and frequency of direct and mediated social contacts under specific conditions of relative social isolation.

  6. Treatment of endometriosis with local acetylsalicylic acid injection: experimental study in rabbits.

    PubMed

    Siqueira, Juliana Menezes; Barreto, Adriana Beatriz; Saad-Hossne, Rogério

    2011-01-01

    The objective of the present study was to estimate the effects of introduction of acetylsalicylic acid solution into peritoneal implants in autologous endometrium as a method for treating endometriosis. Forty adult female rabbits were subdivided into 4 groups of 10 rabbits each, and endometriosis was induced via autotransplantation of endometrial fragments into the peritoneal cavity. At 30 days after induction of endometriosis, all animals were randomly assigned to 1 of 2 protocols. In protocol 1, animals were evaluated at 24 hours after treatment; group 1 (control) received physiologic solution, and group 2 received acetylsalicylic acid. In protocol 2, animals were evaluated at 10 days after treatment, group 3 (control) and group 4 received acetylsalicylic acid. After measuring the lesion, the endometriotic focus was removed and prepared for mounting on slides for histologic analysis. Imaging software was used for analysis of the total remaining area of endometrial tissue. The affected area in acetylsalicylic acid-treated animals was smaller than that in control animals at 24 hours and 10 days after treatment; a significant difference was found between control and treated groups (p < .001). Statistical analysis comparing protocols 1 and 2 demonstrated no differences between controls groups or acetylsalicylic acid groups (p = .30), and no differences between times (p = .75). Acetylsalicylic acid solution led to less growth (or higher involution) of endometrial implants. Acetylsalicylic acid injected directly into endometriotic foci was effective in their destruction. This presents new perspectives for treatment of endometriosis and for clinical applications based on further clinical studies.

  7. National German Guideline (S2k): Guideline for the Diagnosis and Treatment of Endometriosis*

    PubMed Central

    Ulrich, U.; Buchweitz, O.; Greb, R.; Keckstein, J.; von Leffern, I.; Oppelt, P.; Renner, S. P.; Sillem, M.; Stummvoll, W.; De Wilde, R.-L.; Schweppe, K.-W.

    2014-01-01

    In this guideline, recommendations and standards for optimum diagnosis and treatment of endometriosis are presented. They are based on the analysis of the available scientific evidence as published in prospective randomized and retrospective studies as well as in systematic reviews. The guideline working group consisted of experts from Austria, Germany, Switzerland, and the Czech Republic. PMID:26157194

  8. Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility.

    PubMed

    Szczepańska, Malgorzata; Mostowska, Adrianna; Wirstlein, Przemyslaw; Skrzypczak, Jana; Misztal, Matthew; Jagodziński, Paweł P

    2015-11-01

    It has recently been reported that vitamin D blood plasma levels are associated with reduced risk of endometriosis. The present study aimed to investigate whether the vitamin D binding protein (GC), vitamin D receptor (VDR), and retinoid X receptor (RXR) gene variants may be genetic risk factors for endometriosis‑associated infertility. The subjects consisted of 154 women with endometriosis‑associated infertility and 347 controls. Using polymerase chain reaction restriction fragment length polymorphism and high resolution melt techniques, the GC rs1155563, rs2298849 and rs7041; RXRA rs10881578, rs10776909 and rs749759; VDR BsmI rs1544410; and FokI rs2228570 single nucleotide polymorphisms (SNPs) were investigated in the patients with endometriosis and the healthy controls. The results indicated that no significant differences were observed between the genotype and allele frequencies of all experimental SNPs in the vitamin D signaling pathway genes in women with endometriosis-associated infertility and controls. However, a significant association was present between the A‑T haplotype, consisting of VDR rs1544410 and rs222857 minor alleles, and endometriosis-associated infertility [OR=1.659 (1.122‑2.453), P=0.011]. The results of the present study suggested that VDR gene variants act as genetic risk factors for endometriosis‑associated infertility.

  9. Pregnancy Rate after Controlled Ovarian Hyperstimulation and Intrauterine Insemination for the Treatment of Endometriosis following Surgery

    PubMed Central

    Keresztúri, Attila; Kozinszky, Zoltan; Daru, József; Pásztor, Norbert; Sikovanyecz, János; Zádori, János; Márton, Virág; Koloszár, Sándor; Szöllősi, János; Németh, Gábor

    2015-01-01

    Objective. To compare pregnancy rate after controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) with no treatment in patients with endometriosis-associated infertility treated with laparoscopy. Design. A clinical cohort study. Setting. University-level tertiary care center. Patients. 238 women with various stages of endometriosis after laparoscopic treatment. Interventions. Either COH-IUI or follow-up for 12 months. Main Outcome Measures. The primary outcome measures were clinical pregnancy and live birth rate. Predictive factors evaluated were female age, maternal BMI, and duration of infertility. Results. The pregnancy rate attained after the integrated laparoscopy–COH-IUI approach was 53.4%, while it was significantly lower (38.5%) in the control group. Similarly, a significant difference was observed in live births (48.3% versus 34.2%). Patients with severe endometriosis were less likely to achieve pregnancy (38%) and live birth (35%) than their counterparts with milder forms (57% and 53%). Conclusions. In patients with endometriosis-based infertility, surgery followed by COH-IUI is more effective than surgery alone. PMID:26247014

  10. Advantages of the robotic approach to deep infiltrating rectal endometriosis: because less is more.

    PubMed

    Araujo, Sergio Eduardo Alonso; Seid, Victor Edmond; Marques, Renato Moretti; Gomes, Mariano Tamura Vieira

    2016-06-01

    For symptomatic deep infiltrating endometriosis, surgery is often required to achieve symptom relief and restore fertility. A minimally invasive approach using laparoscopy is considered the gold standard. However, specific limitations of the laparoscopic approach deep in the pelvis keep challenging even surgeons with a solid experience with minimally invasive techniques. Robotic surgery has the potential to compensate for technical drawbacks inherent in conventional laparoscopic surgery, such as limited degree of freedom, two-dimensional vision, and the fulcrum effect. In the present report, we aim at demonstrating the central role of robotic surgery for deep infiltrating endometriosis, with special emphasis in the ability to practice organ (rectal) preservation. A 45-year-old white female with a 4-month history of chronic pelvic pain, dyschezia, and dysmenorrhea, refractory to hormonal therapy was referred to our unit. MRI findings were diagnostic of deep infiltrating endometriosis (retrocervical and rectovaginal) extending to the anterior rectal serosal layer (partial-thickness rectal invasion). Using a fully robotic approach, appropriate dissection of the rectovaginal septum and of the extraperitoneal rectum followed by complete excision of the endometriotic rectal nodule with organ (rectal) preservation was undertaken. It is our belief that using a robotic approach, the potential to boost rectal preservation might be established. Moreover, it is possible that in many cases, a robotic operation may allow the surgeon to perform the intervention with greater accuracy and comfort. As a result, more patients with deep infiltrating endometriosis may benefit from rectal sparing procedures.

  11. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

    PubMed

    Guerriero, S; Condous, G; van den Bosch, T; Valentin, L; Leone, F P G; Van Schoubroeck, D; Exacoustos, C; Installé, A J F; Martins, W P; Abrao, M S; Hudelist, G; Bazot, M; Alcazar, J L; Gonçalves, M O; Pascual, M A; Ajossa, S; Savelli, L; Dunham, R; Reid, S; Menakaya, U; Bourne, T; Ferrero, S; Leon, M; Bignardi, T; Holland, T; Jurkovic, D; Benacerraf, B; Osuga, Y; Somigliana, E; Timmerman, D

    2016-09-01

    The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

  12. Generative models: Human embryonic stem cells and multiple modeling relations.

    PubMed

    Fagan, Melinda Bonnie

    2016-04-01

    Model organisms are at once scientific models and concrete living things. It is widely assumed by philosophers of science that (1) model organisms function much like other kinds of models, and (2) that insofar as their scientific role is distinctive, it is in virtue of representing a wide range of biological species and providing a basis for generalizations about those targets. This paper uses the case of human embryonic stem cells (hESC) to challenge both assumptions. I first argue that hESC can be considered model organisms, analogous to classic examples such as Escherichia coli and Drosophila melanogaster. I then discuss four contrasts between the epistemic role of hESC in practice, and the assumptions about model organisms noted above. These contrasts motivate an alternative view of model organisms as a network of systems related constructively and developmentally to one another. I conclude by relating this result to other accounts of model organisms in recent philosophy of science.

  13. Memory-related brain lateralisation in birds and humans.

    PubMed

    Moorman, Sanne; Nicol, Alister U

    2015-03-01

    Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation.

  14. Rehabilitation in adults with human immunodeficiency virus-related diseases.

    PubMed

    O'Dell, M W; Dillon, M E

    1992-06-01

    The acquired immunodeficiency syndrome is a fatal disorder of cell-mediated immunity caused by the human immunodeficiency virus (HIV). As many as one million Americans infected with HIV can expect improved survival with more advanced treatment approaches. Complications of HIV infection occur in the brain, spinal cord, muscle, nerve, joints and other organ systems, which lead to extensive impairments. As survival increases, rehabilitation professionals can anticipate a greater number of referrals for the assessment and management of physical disability in persons with HIV infection. This article reviews HIV-related disease, impairment, disability and handicap pertinent to rehabilitation medicine. An agenda for future research is also proposed. Current knowledge and models or rehabilitation care can be applied to HIV-related physical disability in an effort to improve overall quality of life.

  15. Structural studies of human glioma pathogenesis-related protein 1.

    PubMed

    Asojo, Oluwatoyin A; Koski, Raymond A; Bonafé, Nathalie

    2011-10-01

    Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn2+ complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn2+ similarly to snake-venom CRISPs, which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  16. Relating human productivity and annoyance to indoor noise criteria systems

    NASA Astrophysics Data System (ADS)

    Bowden, Erica E.; Wang, Lily M.

    2004-05-01

    The goal of this research is to determine a noise criteria system which best relates the effects of background noise to human productivity and annoyance. A number of indoor noise criteria systems are currently used to rate the background noise in built environments, including noise criteria (NC), balanced noise criteria (NCB), room criteria (RC), room criteria Mark II (RC-Mark II), and others. Many questions still remain about the accuracy of these predictors in assessing human response to background noise under the variety of ambient noise situations encountered. To support the use of any individual criterion, subjective testing was performed under a range of background noise situations and statistically related to the various noise criteria predictors listed above. Subjects completed an annoyance survey and performed typing and proofreading tasks in an acoustically controlled environment under 12 simulated background noise settings. These settings varied across three sound levels and four spectral qualities. Subjective testing methodology and results are presented. [Work supported by INCE and ASHRAE.

  17. Unified phase variables of relative degree two for human locomotion.

    PubMed

    Villarreal, Dario J; Gregg, Robert D; Villarreal, Dario J; Gregg, Robert D; Gregg, Robert D; Villarreal, Dario J

    2016-08-01

    A starting point to achieve stable locomotion is synchronizing the leg joint kinematics during the gait cycle. Some biped robots parameterize a nonlinear controller (e.g., input-output feedback linearization) whose main objective is to track specific kinematic trajectories as a function of a single mechanical variable (i.e., a phase variable) in order to allow the robot to walk. A phase variable capable of parameterizing the entire gait cycle, the hip phase angle, has been used to control wearable robots and was recently shown to provide a robust representation of the phase of human gait. However, this unified phase variable relies on hip velocity, which is difficult to measure in real-time and prevents the use of derivative corrections in phase-based controllers for wearable robots. One derivative of this phase variable yields accelerations (i.e., the equations of motion), so the system is said to be relative degree-one. This means that there are states of the system that cannot be controlled. The goal of this paper is to offer relative degree-two alternatives to the hip phase angle and examine their robustness for parameterizing human gait.

  18. Thyroid-Related Protein Expression in the Human Thymus

    PubMed Central

    Park, Do Joon; Jung, Kyeong Cheon

    2017-01-01

    Radioiodine whole body scan (WBS), related to sodium iodide symporter (NIS) function, is widely used to detect recurrence/metastasis in postoperative patients with thyroid cancer. However, the normal thymic uptake of radioiodine has occasionally been observed in young patients. We evaluated the expression of thyroid-related genes and proteins in the human thymus. Thymic tissues were obtained from 22 patients with thyroid cancer patients of all ages. The expression of NIS, thyroid-stimulating hormone receptor (TSHR), thyroperoxidase (TPO), and thyroglobulin (Tg) was investigated using immunohistochemistry and quantitative RT-PCR. NIS and TSHR were expressed in 18 (81.8%) and 19 samples (86.4%), respectively, whereas TPO was expressed in five samples (22.7%). Three thyroid-related proteins were localized to Hassall's corpuscles and thymocytes. In contrast, Tg was detected in a single patient (4.5%) localized to vascular endothelial cells. The expression of thyroid-related proteins was not increased in young thymic tissues compared to that in old thymic tissues. In conclusion, the expression of NIS and TSHR was detected in the majority of normal thymus samples, whereas that of TPO was detected less frequently, and that of Tg was detected rarely. The increased thymic uptake of radioiodine in young patients is not due to the increased expression of NIS. PMID:28386277

  19. Supporting and Inhibiting Factors When Coping with Endometriosis From the Patientsʼ Perspective

    PubMed Central

    Kundu, S.; Wildgrube, J.; Schippert, C.; Hillemanns, P.; Brandes, I.

    2015-01-01

    Aim: Endometriosis is a chronic gynaecological disorder with manifold symptoms and psychosocial effects on the lives of affected women. The prevalence of endometriosis is estimated to be up to ten percent of women of reproductive age. As a result of its unclear aetiology, only limited treatment options are available. The treatment and care of affected women is therefore a challenge for their doctors. There is a need for healthcare services to provide affected women with support to cope with the disorder better. The aim of the study was to identify supporting and inhibiting factors on disease management to develop new support ideas. Materials and Methods: The results are based on a content analysis evaluation of text responses from 135 women with confirmed endometriosis. Open questions about disease management were posed in a patient questionnaire. A classification system was developed according to Mayrings Qualitative Content Analysis, which allowed the main topics to be identified and summarised qualitatively using a quantitative intermediate step. Results: Social support, treatment, as well as professional and healthcare system performance were found to be particularly supportive by patients. However, when questioned about inhibiting factors, healthcare system professionals and their performance were most commonly criticised. Just over 50 % of women expressed their criticism of doctors. Quality of care and empathy towards the patients were especially criticised. There is also a need for improvement with regard to communication and general support from doctors. The results illustrate the importance of doctors for women affected by endometriosis, but make it clear that there is a great need for improvement with regard to the profession. Conclusion: The results provide the first indication of problem areas in the management of endometriosis from which approaches could be developed to improve care. However, it must be pointed out that the perspective of affected

  20. Aromatase Inhibitors for Endometriosis-Associated Infertility; Do We Have Sufficient Evidence?

    PubMed Central

    Abu Hashim, Hatem

    2016-01-01

    Orally active aromatase inhibitors (AIs) have gained attention for treatment of infertile women with endometriosis in whom aromatase p450 is aberrantly expressed. This review aimed to critically appraise and summarize the available evidence concerning the use of AIs for management of endometriosis-associated infertility. PubMed was searched to May 2015 with the following key words: endometriosis, infertility and aromatase. Priority was given for randomized controlled trials (RCTs) followed by other study designs. Main outcome measures were as follows: rates of clinical pregnancy, miscarriage and live birth as well as endocrine outcomes. Eighty-two abstracts were screened and six original articles were included. A RCT demonstrated that post-operative letrozole treatment did not improve spontaneous pregnancy rate. Another RCT reported no superiority of letrozole superovulation over clomiphene citrate (each combined with intrauterine insemination) in minimalmild endometriosis and previous laparoscopic treatment. Anastrozole significantly inhibited the growth of endometriotic cells and their estrogen production in culture. In assisted reproductive technology (ART) cycles, dual suppression (Agonist/anastrozole) was tested in a pilot study with a pregnancy rate of 45% however, high pregnancy loss (30%) occurred. A retrospective study showed that letrozole may improve endometrial receptivity in endometriotic patients undergoing in vitro fertilization (IVF). An opposite view from an in vitro study showed lower estradiol production and aromatase expression in cultured granulosa cells from endometriotic women undergoing IVF and marked reduction under letrozole. In conclusion, current evidence is limited. More trials are warranted to enhance our knowledge and provide a clear and unequivocal evidence to guide our clinical management of infertile women with endometriosis using AIs. PMID:27695608

  1. 'Waiting for Godot': a commonsense approach to the medical treatment of endometriosis.

    PubMed

    Vercellini, Paolo; Crosignani, PierGiorgio; Somigliana, Edgardo; Viganò, Paola; Frattaruolo, Maria Pina; Fedele, Luigi

    2011-01-01

    Conservative surgical treatment for symptomatic endometriosis is frequently associated with only partial relief of pelvic pain or its recurrence. Therefore, medical therapy constitutes an important alternative or complement to surgery. However, no available compound is cytoreductive, and suppression instead of elimination of implants is the only realistic objective of pharmacological intervention. Because this implies prolonged periods of treatments, only medications with a favourable safety/tolerability/efficacy/cost profile should be chosen. In the past few years, innumerable new drugs for endometriosis, which would interfere with several hypothesized pathogenic mechanisms, have been studied and their use foreseen. However, robust evidence of in vivo safety and efficacy is lacking and, at the moment, the principal modality to interfere with endometriosis metabolism is still hormonal manipulation. Regrettably, in spite of consistent demonstration of a major effect on pain even in patients with deeply infiltrating lesions, progestins are underestimated and dismissed in favour of more scientifically fashionable and up-to-the-minute alternatives. Moreover, oral contraceptives (OCs) dramatically reduce the rate of post-operative endometrioma recurrence and should now be considered an essential part of long-term therapeutic strategies in order to limit further damage to future fertility. Finally, women who have used OC for prolonged periods will be protected from an increased risk of endometriosis-associated ovarian cancer. To avoid the several subtle modalities for distorting facts and orientating opinions in favour of specific compounds, progestins and monophasic OC used continuously are here proposed as the reference comparator in all future randomized controlled trials on medical treatment for endometriosis.

  2. Endometriosis as a detrimental condition for granulosa cell steroidogenesis and development: From molecular alterations to clinical impact.

    PubMed

    Sanchez, Ana Maria; Somigliana, Edgardo; Vercellini, Paolo; Pagliardini, Luca; Candiani, Massimo; Vigano, Paola

    2016-01-01

    Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period. Alterations in ovarian follicle morphology and function have been documented in affected women. The local intrafollicular environment has been as well examined by various groups. In the present review, we aimed to summarize the molecular evidence supporting the idea that endometriosis can negatively influence growth, steroidogenesis and the function of the granulosa cells (GCs). Reduced P450 aromatase expression, increased intracellular ROS generation and altered WNT signaling characterize the GCs of women with endometriosis. Clear evidence for an increased level of GC apoptosis has been provided in association with the downregulation of pro-survival factors. Other potentially negative effects include decreased progesterone production, locally decreased AMH production and lower inflammatory cytokine expression, although these have been only partially clarified. The possibility that endometriosis per se may influence IVF clinical results as a consequence of the detrimental impact on the local intrafollicular environment is also discussed.

  3. Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study

    PubMed Central

    Yuk, Jin-Sung; Shin, Jong Seung; Shin, Ji-Yeon; Oh, Eunsuk; Kim, Hyunmee; Park, Won I.

    2015-01-01

    Background A cross-sectional study has reported that nickel allergy is associated with endometriosis. However, causal studies of this association are limited. Objective The objective of this study was to compare the prevalence of nickel allergy in women with and without endometriosis. Methods We used a National Health Insurance Service (NHIS) sample cohort dataset that included approximately 1 million individuals from South Korea; the data were obtained between January 01, 2002, and December 31, 2013. We selected the endometriosis group according to diagnosis code (N80.X), surgery codes, and drug codes during the years 2009~2013. The controls were randomly matched to the endometriosis patients at a ratio of 4:1 by age and socioeconomic status. Patients with nickel allergy were defined in the cohort dataset as those with a simultaneous diagnosis code (L23.0) and patch test code during 2002~2008. Results In total, 4,985 women were selected from the NHIS cohort database and divided into an endometriosis group (997 women) and a control group (3,988 women). The number of patients with nickel allergy in the endometriosis group was eight (0.8%), and that in the control group was thirteen (0.3%). After adjustment for age and socioeconomic status, the rate of nickel allergy in was higher in the endometriosis group than in the control group [odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044]. Conclusions We found that nickel allergy is a risk factor for endometriosis. PMID:26439741

  4. Molecular Classification of Endometriosis and Disease Stage Using High-Dimensional Genomic Data

    PubMed Central

    Tamaresis, John S.; Irwin, Juan C.; Goldfien, Gabriel A.; Rabban, Joseph T.; Burney, Richard O.; Nezhat, Camran; DePaolo, Louis V.

    2014-01-01

    Endometriosis (E), an estrogen-dependent, progesterone-resistant, inflammatory disorder, affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Because the uterine lining (endometrium) in women with E has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n = 148 archived endometrial samples from women with E or without E (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with E or no E involved 2 binary decisions, each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no E from E, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified E with 90%–100% accuracy, were cycle phase-specific or independent, and used relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism, and growth factor signaling in endometrium of women with E. Similar findings were observed with other disorders vs controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic E with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular

  5. Endometriosis is associated with progesterone resistance in the baboon (Papio anubis) oviduct: evidence based on the localization of oviductal glycoprotein 1 (OVGP1).

    PubMed

    Wang, Chaohua; Mavrogianis, Patricia A; Fazleabas, Asgerally T

    2009-02-01

    Endometriosis has been associated with a reduced response to progesterone in both the eutopic and ectopic endometrium. In this study we evaluated OVGP1 and steroid receptor expression in oviducts of baboons with endometriosis during the midsecretory phase and determined whether progesterone resistance associated with endometriosis also occurs in the oviduct. Oviducts obtained during the window of uterine receptivity (Day 10 postovulation [PO]) from animals with induced and spontaneous disease were compared to control animals during the proliferative stage and in the implantation window as well as animals treated with the progesterone receptor (PGR) antagonist ZK 137.299 (ZK). OVGP1 was significantly higher in animals with endometriosis compared with Day 10 PO controls and was similar to that seen in the late proliferative phase and in ZK-treated animals. Baboons with spontaneous endometriosis also showed a similar persistence of OVGP1, which was correlated with the maintenance of estrogen receptor 1 (ESR1) in the epithelial cells of animals with endometriosis. However, epithelial cell height and the percentage of ciliation were not affected by endometriosis. These data imply that the normal antagonism of progesterone on ESR and OVGP1, which results in their downregulation during the window of implantation, is absent in animals with endometriosis. This was confirmed further when the action of PGR was antagonized in animals without disease, which also resulted in the persistence of ESR1 and OVGP1. These studies suggest that an aberrant oviductal environment may be an additive factor that contributes to endometriosis-associated infertility.

  6. Expression patterns of progesterone receptor membrane components 1 and 2 in endometria from women with and without endometriosis.

    PubMed

    Bunch, Kristen; Tinnemore, Deborah; Huff, Seth; Hoffer, Zachary S; Burney, Richard O; Stallings, Jonathan D

    2014-02-01

    Endometriosis is a hormone-dependent inflammatory condition associated with pain and infertility. A growing body of evidence supports attenuated secretory-phase progesterone responsiveness in women with this disease. Herein, we compare the expression of progesterone receptor membrane components (PGRMC) 1 and 2 in eutopic endometrium from 11 women with laparoscopically and/or histologically proven stage III/IV endometriosis and 23 disease-free women. Menstrual cycle phase was determined using a combination of reported cycle day, serum hormone profile, and endometrial histologic dating. The PGRMC-1 (fold change -3.3; P < .05) and PGRMC-2 (fold-change -8.8; P < .05) gene expression were significantly downregulated in secretory phase, eutopic endometrium from women with endometriosis. Immunohistochemistry demonstrated decreased PGRMC-1 and PGRMC-2 protein expression in the secretory phase endometrial stroma cells of women with endometriosis. Consistent with the preclinical work of others, our results reflect downregulation of endometrial PGRMC-1 and PGRMC-2 expression in secretory phase endometrium from women with advanced stage endometriosis. Understanding the molecular mechanisms of attenuated progesterone action in endometriosis has important diagnostic and therapeutic implications.

  7. COX-2 gene promoter DNA methylation status in eutopic and ectopic endometrium of Egyptian women with endometriosis.

    PubMed

    Zidan, Haidy E; Rezk, Noha A; Alnemr, Amr Abd Almohsen; Abd El Ghany, Amany M

    2015-11-01

    The pathophysiology of COX-2 expression in endometriosis is a matter of debate. The aim was to investigate the role of DNA methylation of the NF-IL6 site within the promoter of COX-2 gene in the pathogenesis of endometriosis. The endometrial tissues (ectopic and eutopic) were collected from 60 women with endometriosis and 30 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation-specific PCR. Quantitative real-time PCR (RT-PCR) was performed to measure COX-2 mRNA levels in endometrial tissues. We found significantly higher levels of COX-2 in ectopic endometriotic tissue compared with eutopic tissue. Also, we found that the frequencies of methylation status of the NF-IL6 site within the COX-2 promoter in the eutopic and ectopic endometrial tissues of endometriosis groups were significantly decreased in comparison to controls (P=0.002, P=0.000 respectively). Our study demonstrated that DNA hypomethylation of the NF-IL6 site within the promoter of COX-2 gene could be a key mechanism for its elevated expression in the eutopic and ectopic tissues of endometriosis.

  8. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids.

    PubMed Central

    McLaren, J; Prentice, A; Charnock-Jones, D S; Millican, S A; Müller, K H; Sharkey, A M; Smith, S K

    1996-01-01

    Angiogenesis is important in the pathophysiology of endometriosis, a condition characterized by implantation of ectopic endometrium in the peritoneal cavity. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in physiological and pathological angiogenesis, and elevated levels of VEGF are found in peritoneal fluid of patients with endometriosis. Our aim was to investigate the site of expression and regulation of VEGF in endometriosis. VEGF immunoreactivity was found in tissue macrophages present in ectopic endometrium and in activated peritoneal fluid macrophages. Macrophage activation was highest in women with endometriosis, and media conditioned by peritoneal fluid macrophages from these women caused a VEGF-dependent increase in endothelial cell proliferation above that seen from normal women. Peritoneal fluid macrophages secreted VEGF in response to ovarian steroids, and this secretion was enhanced after activation with lipopolysaccharide. Peritoneal fluid macrophages expressed receptors for steroid hormones. VEGF receptors flt and KDR (kinase domain receptor) were also detected, suggesting autocrine regulation. During the menstrual cycle, expression of flt was constant but that of KDR was increased in the luteal phase, at which time the cells migrated in response to VEGF. KDR expression and the migratory response were significantly higher in patients with endometriosis. This study demonstrates that activated macrophages are a major source of VEGF in endometriosis and that this expression is regulated directly by ovarian steroids. PMID:8755660

  9. mRNA TLR2 AND TLR4 EXPRESSION IN THE ENDOMETRIUM TISSUE IN WOMEN WITH ENDOMETRIOSIS ASSOSIATED WITH INFERTILITY.

    PubMed

    Koval, H; Chopiak, V; Kamyshnyi, А

    2015-01-01

    Endometriosis is an important medical and social problem as it causes stable pelvic pains, afflicts women of the reproductive age, provokes infertility characterized by poor outcome of treatment. In recent times much attention is paid to the mechanisms of congenital immunity as possible mediators of the development of endometriosis and targets of therapy. The work deals with the investigation of the levels of mRNA TLR2 and TLR4 expression in the tissue of eutopic endometrium in women with endometriosis and infertility in comparison with women afflicted with infertility of a tubular character with the aim to define the role of TLR2 and TLR4 in the development of infertility in case of endometriosis. The study was conducted by means of polymerase chain reaction (PCR) real-time method. The results of the study are indicative of an increased TLR2 and TLR4 expression (especially TLR2) in the endometrium in women with endometriosis. The results obtained may be indicative of an important role of TLR2 and TLR4 in the development of endometrioid ectopia and should be considered while treating infertility in women with endometriosis.

  10. Human crew-related aspects for astrobiology research

    NASA Astrophysics Data System (ADS)

    Thiel, Cora S.; Pletser, Vladimir; Foing, Bernard

    2011-07-01

    Several space agencies and exploration stakeholders have a strong interest in obtaining information on technical and human aspects to prepare for future extra-terrestrial planetary exploration. In this context, the EuroGeoMars campaign, organized with support from the International Lunar Exploration Working Group (ILEWG), the European Space Agency (ESA), the National Aeronautics and Space Administration (NASA) Ames Research Center and partner institutes, was conducted by the crews 76 and 77 in February 2009 in The Mars Society's ‘Mars Desert Research Station’ (MDRS) in Utah. The EuroGeoMars encompasses two groups of experiments: (1) a series of field science experiments that can be conducted from an extra-terrestrial planetary surface in geology, biology, astronomy/astrophysics and the necessary technology and networks to support these field investigations; (2) a series of human crew-related investigations on crew time organization in a planetary habitat, on the different functions and interfaces of this habitat, and on man-machine interfaces of science and technical equipment. This paper recalls the objective of the EuroGeoMars project and presents the MDRS and its habitat layout. Social and operational aspects during simulations are described. Technical and operational aspects of biology investigations in the field and in the habitat laboratory are discussed in detail with the focus point set on the polymerase chain reaction (PCR)-based detection of microbial DNA in soil samples.

  11. Primary function analysis of human mental retardation related gene CRBN.

    PubMed

    Xin, Wang; Xiaohua, Ni; Peilin, Chen; Xin, Chen; Yaqiong, Sun; Qihan, Wu

    2008-06-01

    The mutation of human cereblon gene (CRBN) is revealed to be related with mild mental retardation. Since the molecular characteristics of CRBN have not been well presented, we investigated the general properties of CRBN. We analyzed its gene structure and protein homologues. The CRBN protein might belong to a family of adenosine triphosphate (ATP)-dependent Lon protease. We also found that CRBN was widely expressed in different tissues, and the expression level in testis is significantly higher than other tissues. This may suggested it could play some important roles in several other tissues besides brain. Transient transfection experiment in AD 293 cell lines suggested that both CRBN and CRBN mutant (nucleotide position 1,274(C > T)) are located in the whole cells. This may suggest new functions of CRBN in cell nucleolus besides its mitochondria protease activity in cytoplasm.

  12. Absolutely relative or relatively absolute: violations of value invariance in human decision making.

    PubMed

    Teodorescu, Andrei R; Moran, Rani; Usher, Marius

    2016-02-01

    Making decisions based on relative rather than absolute information processing is tied to choice optimality via the accumulation of evidence differences and to canonical neural processing via accumulation of evidence ratios. These theoretical frameworks predict invariance of decision latencies to absolute intensities that maintain differences and ratios, respectively. While information about the absolute values of the choice alternatives is not necessary for choosing the best alternative, it may nevertheless hold valuable information about the context of the decision. To test the sensitivity of human decision making to absolute values, we manipulated the intensities of brightness stimuli pairs while preserving either their differences or their ratios. Although asked to choose the brighter alternative relative to the other, participants responded faster to higher absolute values. Thus, our results provide empirical evidence for human sensitivity to task irrelevant absolute values indicating a hard-wired mechanism that precedes executive control. Computational investigations of several modelling architectures reveal two alternative accounts for this phenomenon, which combine absolute and relative processing. One account involves accumulation of differences with activation dependent processing noise and the other emerges from accumulation of absolute values subject to the temporal dynamics of lateral inhibition. The potential adaptive role of such choice mechanisms is discussed.

  13. Human attribute concepts: relative ubiquity across twelve mutually isolated languages.

    PubMed

    Saucier, Gerard; Thalmayer, Amber Gayle; Bel-Bahar, Tarik S

    2014-07-01

    It has been unclear which human-attribute concepts are most universal across languages. To identify common-denominator concepts, we used dictionaries for 12 mutually isolated languages-Maasai, Supyire Senoufo, Khoekhoe, Afar, Mara Chin, Hmong, Wik-Mungkan, Enga, Fijian, Inuktitut, Hopi, and Kuna-representing diverse cultural characteristics and language families, from multiple continents. A composite list of every person-descriptive term in each lexicon was closely examined to determine the content (in terms of English translation) most ubiquitous across languages. Study 1 identified 28 single-word concepts used to describe persons in all 12 languages, as well as 41 additional terms found in 11 of 12. Results indicated that attribute concepts related to morality and competence appear to be as cross-culturally ubiquitous as basic-emotion concepts. Formulations of universal-attribute concepts from Osgood and Wierzbicka were well-supported. Study 2 compared lexically based personality models on the relative ubiquity of key associated terms, finding that 1- and 2-dimensional models draw on markedly more ubiquitous terms than do 5- or 6-factor models. We suggest that ubiquitous attributes reflect common cultural as well as common biological processes.

  14. Rapidly quantifying the relative distention of a human bladder

    NASA Technical Reports Server (NTRS)

    Companion, John A. (Inventor); Heyman, Joseph S. (Inventor); Mineo, Beth A. (Inventor); Cavalier, Albert R. (Inventor); Blalock, Travis N. (Inventor)

    1989-01-01

    A device and method of rapidly quantifying the relative distention of the bladder in a human subject are disclosed. The ultrasonic transducer which is positioned on the subject in proximity to the bladder is excited by a pulser under the command of a microprocessor to launch an acoustic wave into the patient. This wave interacts with the bladder walls and is reflected back to the ultrasonic transducer, when it is received, amplified and processed by the receiver. The resulting signal is digitized by an analog-to-digital converter under the command of the microprocessor and is stored in the data memory. The software in the microprocessor determines the relative distention of the bladder as a function of the propagated ultrasonic energy; and based on programmed scientific measurements and individual, anatomical, and behavioral characterists of the specific subject as contained in the program memory, sends out a signal to turn on any or all of the audible alarm, the visible alarm, the tactile alarm, and the remote wireless alarm.

  15. Autophagy and lysosomal related protein expression patterns in human glioblastoma.

    PubMed

    Giatromanolaki, Alexandra; Sivridis, Efthimios; Mitrakas, Achileas; Kalamida, Dimitra; Zois, Christos E; Haider, Syed; Piperidou, Charitomeni; Pappa, Aglaia; Gatter, Kevin C; Harris, Adrian L; Koukourakis, Michael I

    2014-01-01

    Glioblastoma cells are resistant to apoptotic stimuli with autophagic death prevailing under cytotoxic stress. Autophagy interfering agents may represent a new strategy to test in combination with chemo-radiation. We investigated the patterns of expression of autophagy related proteins (LC3A, LC3B, p62, Beclin 1, ULK1 and ULK2) in a series of patients treated with post-operative radiotherapy. Experiments with glioblastoma cell lines (T98 and U87) were also performed to assess autophagic response under conditions simulating the adverse intratumoral environment. Glioblastomas showed cytoplasmic overexpression of autophagic proteins in a varying extent, so that cases could be grouped into low and high expression groups. 10/23, 5/23, 13/23, 5/23, 8/23 and 9/23 cases examined showed extensive expression of LC3A, LC3B, Beclin 1, Ulk 1, Ulk 2 and p62, respectively. Lysosomal markers Cathepsin D and LAMP2a, as well as the lyososomal biogenesis transcription factor TFEB were frequently overexpressed in glioblastomas (10/23, 11/23, and 10/23 cases, respectively). TFEB was directly linked with PTEN, Cathepsin D, HIF1α, LC3B, Beclin 1 and p62 expression. PTEN was also significantly related with LC3B but not LC3A expression, in both immunohistochemistry and gene expression analysis. Confocal microscopy in T98 and U87 cell lines showed distinct identity of LC3A and LC3B autophagosomes. The previously reported stone-like structure (SLS) pattern of LC3 expression was related with prognosis. SLS were inducible in glioblastoma cell lines under exposure to acidic conditions and 2DG mediated glucose antagonism. The present study provides the basis for autophagic characterization of human glioblastoma for further translational studies and targeted therapy trials.

  16. Human Brain Activity Related to the Tactile Perception of Stickiness.

    PubMed

    Yeon, Jiwon; Kim, Junsuk; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    While the perception of stickiness serves as one of the fundamental dimensions for tactile sensation, little has been elucidated about the stickiness sensation and its neural correlates. The present study investigated how the human brain responds to perceived tactile sticky stimuli using functional magnetic resonance imaging (fMRI). To evoke tactile perception of stickiness with multiple intensities, we generated silicone stimuli with varying catalyst ratios. Also, an acrylic sham stimulus was prepared to present a condition with no sticky sensation. From the two psychophysics experiments-the methods of constant stimuli and the magnitude estimation-we could classify the silicone stimuli into two groups according to whether a sticky perception was evoked: the Supra-threshold group that evoked sticky perception and the Infra-threshold group that did not. In the Supra-threshold vs. Sham contrast analysis of the fMRI data using the general linear model (GLM), the contralateral primary somatosensory area (S1) and ipsilateral dorsolateral prefrontal cortex (DLPFC) showed significant activations in subjects, whereas no significant result was found in the Infra-threshold vs. Sham contrast. This result indicates that the perception of stickiness not only activates the somatosensory cortex, but also possibly induces higher cognitive processes. Also, the Supra- vs. Infra-threshold contrast analysis revealed significant activations in several subcortical regions, including the pallidum, putamen, caudate and thalamus, as well as in another region spanning the insula and temporal cortices. These brain regions, previously known to be related to tactile discrimination, may subserve the discrimination of different intensities of tactile stickiness. The present study unveils the human neural correlates of the tactile perception of stickiness and may contribute to broadening the understanding of neural mechanisms associated with tactile perception.

  17. Human Brain Activity Related to the Tactile Perception of Stickiness

    PubMed Central

    Yeon, Jiwon; Kim, Junsuk; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    While the perception of stickiness serves as one of the fundamental dimensions for tactile sensation, little has been elucidated about the stickiness sensation and its neural correlates. The present study investigated how the human brain responds to perceived tactile sticky stimuli using functional magnetic resonance imaging (fMRI). To evoke tactile perception of stickiness with multiple intensities, we generated silicone stimuli with varying catalyst ratios. Also, an acrylic sham stimulus was prepared to present a condition with no sticky sensation. From the two psychophysics experiments–the methods of constant stimuli and the magnitude estimation—we could classify the silicone stimuli into two groups according to whether a sticky perception was evoked: the Supra-threshold group that evoked sticky perception and the Infra-threshold group that did not. In the Supra-threshold vs. Sham contrast analysis of the fMRI data using the general linear model (GLM), the contralateral primary somatosensory area (S1) and ipsilateral dorsolateral prefrontal cortex (DLPFC) showed significant activations in subjects, whereas no significant result was found in the Infra-threshold vs. Sham contrast. This result indicates that the perception of stickiness not only activates the somatosensory cortex, but also possibly induces higher cognitive processes. Also, the Supra- vs. Infra-threshold contrast analysis revealed significant activations in several subcortical regions, including the pallidum, putamen, caudate and thalamus, as well as in another region spanning the insula and temporal cortices. These brain regions, previously known to be related to tactile discrimination, may subserve the discrimination of different intensities of tactile stickiness. The present study unveils the human neural correlates of the tactile perception of stickiness and may contribute to broadening the understanding of neural mechanisms associated with tactile perception. PMID:28163677

  18. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-12-29

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  19. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-12-31

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  20. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-12-30

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  1. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-11-22

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  2. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    PubMed Central

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  3. Relative Valuation of Pain in Human Orbitofrontal Cortex

    PubMed Central

    Vlaev, Ivo; Seymour, Ben; Chater, Nick; Dolan, Raymond J.

    2014-01-01

    The valuation of health-related states, including pain, is a critical issue in clinical practice, health economics, and pain neuroscience. Surprisingly the monetary value people associate with pain is highly context-dependent, with participants willing to pay more to avoid medium-level pain when presented in a context of low-intensity, rather than high-intensity, pain. Here, we ask whether context impacts upon the neural representation of pain itself, or alternatively the transformation of pain into valuation-driven behavior. While undergoing fMRI, human participants declared how much money they would be willing to pay to avoid repeated instances of painful cutaneous electrical stimuli delivered to the foot. We also implemented a contextual manipulation that involved presenting medium-level painful stimuli in blocks with either low- or high-level stimuli. We found no evidence of context-dependent activity within a conventional “pain matrix,” where pain-evoked activity reflected absolute stimulus intensity. By contrast, in right lateral orbitofrontal cortex, a strong contextual dependency was evident, and here activity tracked the contextual rank of the pain. The findings are in keeping with an architecture where an absolute pain valuation system and a rank-dependent system interact to influence willing to pay to avoid pain, with context impacting value-based behavior high in a processing hierarchy. This segregated processing hints that distinct neural representations reflect sensory aspects of pain and components that are less directly nociceptive whose integration also guides pain-related actions. A dominance of the latter might account for puzzling phenomena seen in somatization disorders where perceived pain is a dominant driver of behavior. PMID:25355207

  4. Reconcilable differences? Human diversity, cultural relativity, and sense of community.

    PubMed

    Townley, Greg; Kloos, Bret; Green, Eric P; Franco, Margarita M

    2011-03-01

    Sense of community (SOC) is one of the most widely used and studied constructs in community psychology. As proposed by Sarason in (The Psychological sense of community: prospects for a community psychology, Jossey-Bass, San Francisco, 1974), SOC represents the strength of bonding among community members. It is a valuable component of community life, and it has been linked to positive mental health outcomes, citizen participation, and community connectedness. However, promotion of SOC can become problematic in community psychology praxis when it conflicts with other core values proposed to define the field, namely values of human diversity, cultural relativity, and heterogeneity of experience and perspective. Several commentators have noted that promotion of SOC can conflict with multicultural diversity because it tends to emphasize group member similarity and appears to be higher in homogeneous communities. In this paper, we introduce the idea of a community-diversity dialectic as part of praxis and research in community psychology. We argue that systematic consideration of cultural psychology perspectives can guide efforts to address a community-diversity dialectic and revise SOC formulations that ultimately will invigorate community research and action. We provide a working agenda for addressing this dialectic, proposing that systematic consideration of the creative tension between SOC and diversity can be beneficial to community psychology.

  5. Human heart rate variability relation is unchanged during motion sickness

    NASA Technical Reports Server (NTRS)

    Mullen, T. J.; Berger, R. D.; Oman, C. M.; Cohen, R. J.

    1998-01-01

    In a study of 18 human subjects, we applied a new technique, estimation of the transfer function between instantaneous lung volume (ILV) and instantaneous heart rate (HR), to assess autonomic activity during motion sickness. Two control recordings of ILV and electrocardiogram (ECG) were made prior to the development of motion sickness. During the first, subjects were seated motionless, and during the second they were seated rotating sinusoidally about an earth vertical axis. Subjects then wore prism goggles that reverse the left-right visual field and performed manual tasks until they developed moderate motion sickness. Finally, ILV and ECG were recorded while subjects maintained a relatively constant level of sickness by intermittent eye closure during rotation with the goggles. Based on analyses of ILV to HR transfer functions from the three conditions, we were unable to demonstrate a change in autonomic control of heart rate due to rotation alone or due to motion sickness. These findings do not support the notion that moderate motion sickness is manifested as a generalized autonomic response.

  6. Error-related electrocorticographic activity in humans during continuous movements

    NASA Astrophysics Data System (ADS)

    Milekovic, Tomislav; Ball, Tonio; Schulze-Bonhage, Andreas; Aertsen, Ad; Mehring, Carsten

    2012-04-01

    Brain-machine interface (BMI) devices make errors in decoding. Detecting these errors online from neuronal activity can improve BMI performance by modifying the decoding algorithm and by correcting the errors made. Here, we study the neuronal correlates of two different types of errors which can both be employed in BMI: (i) the execution error, due to inaccurate decoding of the subjects’ movement intention; (ii) the outcome error, due to not achieving the goal of the movement. We demonstrate that, in electrocorticographic (ECoG) recordings from the surface of the human brain, strong error-related neural responses (ERNRs) for both types of errors can be observed. ERNRs were present in the low and high frequency components of the ECoG signals, with both signal components carrying partially independent information. Moreover, the observed ERNRs can be used to discriminate between error types, with high accuracy (≥83%) obtained already from single electrode signals. We found ERNRs in multiple cortical areas, including motor and somatosensory cortex. As the motor cortex is the primary target area for recording control signals for a BMI, an adaptive motor BMI utilizing these error signals may not require additional electrode implants in other brain areas.

  7. Human Aging Is a Metabolome-related Matter of Gender.

    PubMed

    Jové, Mariona; Maté, Ianire; Naudí, Alba; Mota-Martorell, Natalia; Portero-Otín, Manuel; De la Fuente, Mónica; Pamplona, Reinald

    2016-05-01

    A molecular description of the mechanisms by which aging is produced is still very limited. Here, we have determined the plasma metabolite profile by using high-throughput metabolome profiling technologies of 150 healthy humans ranging from 30 to 100 years of age. Using a nontargeted approach, we detected 2,678 metabolite species in plasma, and the multivariate analyses separated perfectly two groups indicating a specific signature for each gender. In addition, there is a set of gender-shared metabolites, which change significantly during aging with a similar tendency. Among the identified molecules, we found vitamin D2-related compound, phosphoserine (40:5), monoacylglyceride (22:1), diacylglyceride (33:2), and resolvin D6, all of them decreasing with the aging process. Finally, we found three molecules that directly correlate with age and seven that inversely correlate with age, independently of gender. Among the identified molecules (6 of 10 according to exact mass and retention time), we found a proteolytic product (l-γ-glutamyl-l-leucine), which increased with age. On the contrary, a hydroxyl fatty acid (25-hydroxy-hexacosanoic), a polyunsaturated fatty acid (eicosapentaenoic acid), two phospholipids (phosphocholine [42:9]and phosphoserine [42:3]) and a prostaglandin (15-keto-prostaglandin F2α) decreased with aging. These results suggest that lipid species and their metabolism are closely linked to the aging process.

  8. Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects.

    PubMed

    Lessey, Bruce A; Lebovic, Dan I; Taylor, Robert N

    2013-03-01

    The endometrium is ground zero when it comes to understanding how implantation occurs and how it might also fail, resulting in infertility or pregnancy loss. Many of the causes of diminished uterine receptivity are acquired during a woman's lifetime. Endometriosis, a major inflammatory disease affecting women, is also a leading cause of infertility and miscarriage. Once established, the inflammatory changes can, in some women, lead to progesterone resistance and downstream changes in endometrial gene expression. Much is now known about how inflammation translates to progesterone resistance and infertility, but much remains to be learned. In this review we provide an overview for understanding how the endometrium becomes dysfunctional, what biomarkers may hold promise for the diagnosis of endometriosis, and how progesterone resistance leads to infertility. Understanding the pathophysiology of this disease will likely lead to better treatment options.

  9. Sacral Neuromodulation: Foray into Chronic Pelvic Pain in End Stage Endometriosis

    PubMed Central

    Suvitie, Pia

    2017-01-01

    Excision of all endometriotic lesions is the method of choice in the treatment of severe endometriosis resistant to medical therapy. The infiltrating nature of the disease as well as extensive surgery may, however, cause chronic pain that cannot be relieved by either surgery or hormonal treatment. As a pilot treatment, we tested the effect of sacral neuromodulation (SNM) for four endometriosis patients suffering chronic pelvic pain and pelvic organ dysfunction after radical surgical treatment. Three out of four patients reported improvement in their symptoms during the neuromodulation testing period and a permanent pulse generator was installed. After 2.5 years, all three patients report better quality of life and want to continue with SNM.

  10. Endometrial adult/progenitor stem cells: pathogenetic theory and new antiangiogenic approach for endometriosis therapy.

    PubMed

    Pittatore, G; Moggio, A; Benedetto, C; Bussolati, B; Revelli, A

    2014-03-01

    The cyclical arrival of endometrial cells into the abdominal cavity through retrograde flux at menstruation represents the etiopathogenetic basis of endometriosis. The endometrium has peculiar regenerative properties linked to the presence of adult stem cells similar to mesenchymal stem cells (MSCs). Once in the abdominal cavity, these MSCs could proliferate, invade, and differentiate into endometrial cells, finally generating ectopic implants. As only differentiated endometrial cells, and not endometrial MSCs, possess steroid hormone receptors, MSCs could be responsible for the high rate of persistence/recurrence of the disease after hypoestrogenism-inducing therapies. Even angiogenesis promoted by MSCs could play an important role, as survival and proliferation of endometriotic tissue depend on the formation of new blood vessels. Inhibition of angiogenesis represents, in fact, a new, promising therapeutic approach for the disease. Further, medications directly targeting endometriosis MSCs could be effective, alone or in association with hormonal treatments, in increasing the success of medical treatment.

  11. Abdominal Wall Endometriosis: Myofibroblasts as a Possible Evidence of Metaplasia: A Case Report.

    PubMed

    Ibrahim, Mohamed Gamal; Delarue, Eleonore; Abesadze, Elene; Haas, Matthias; Sehouli, Jalid; Chiantera, Vito; Mechsner, Sylvia

    2017-01-01

    In this study, we report about a patient with extra-uterine endometriosis (EM) in the abdominal wall muscle with evident metaplasia based on the abundant alpha smooth muscle actin (ASMA)-expressing myofibroblasts. Laparotomy excision of the abdominal wall EM was done following ultrasonographic evidence of a hypodense swelling in the right rectus abdominis, which was confirmed by MRI. Immunohistochemistry staining for ASMA and collagen I was done, with the results confirming that endometriotic stromal cells expressed both. Anterior abdominal wall endometriosis was suspected because of the patient's history of recurrent EM combined with the cyclic nature of symptoms. MRI is useful in determining the extent of the disease. In case of persisting symptoms even under hormonal treatment, surgical excision is mandatory. The expression of both ASMA and collagen I in and around EM lesions supports the notion of the metaplastic process in the course of disease development.

  12. Role of robotic surgery in the management of deep infiltrating endometriosis.

    PubMed

    Sussfeld, Julie; Segaert, An; Rubod, Chrystèle; Collinet, Pierre

    2016-02-01

    Standard laparoscopy (SL) is the gold standard for endometriosis surgery including deep infiltrating endometriosis (DIE). DIE laparoscopic surgery can require complex surgical procedures performed by multidisciplinary surgical team. Robotic assisted laparoscopy (RAL) could offer technical advantages such as 3D vision, tremor filtration and better surgical ergonomy. RAL would be able to improve surgical performances compared to SL, decrease perioperative morbidity and decrease the risk of laparo-conversion. For these reasons, DIE could be one of the best indications for RAL in gynecologic surgery. Demonstrating the feasibility of RAL for DIE surgery, few series of cases have been already published. None of them have demonstrated differences in surgical outcomes. One randomized control trial comparing SL to RAL would be mandatory in order to define potential benefits of RAL for DIE surgery.

  13. Pelvic abscess after oocyte retrieval in women with endometriosis: A case series

    PubMed Central

    Romero, Bárbara; Aibar, Laura; Martínez Navarro, Luis; Fontes, Juan; Calderón, Maria-Angeles; Mozas, Juan

    2013-01-01

    Background: Pelvic inflammatory disease with progression to pelvic abscess is a rare complication after oocyte retrieval during in vitro fertilization cycles. However, in patients with endometriosis the risk appears to be increased. Many authors agree on the need for antibiotic prophylaxis during the oocyte retrieval in these patients, but there is no consensus regarding the best antibiotic. Case: We discuss 3 clinical cases of tubo-ovarian abscess in women with endometriosis after oocyte retrieval despite antibiotic prophylaxis between 2004 and 2011 at our center, and discuss our experience in the context of earlier reports. Conclusion: It is unclear whether antibiotic prophylaxis is necessary in these women, and which antibiotic is best. Only douching with povidone-iodine appears to decrease the rate of pelvic infection. PMID:24639807

  14. The Association between Endometriosis, Tubal Ligation, Hysterectomy and Epithelial Ovarian Cancer: Meta-Analyses

    PubMed Central

    Wang, Chunpeng; Liang, Zhenzhen; Liu, Xin; Zhang, Qian; Li, Shuang

    2016-01-01

    To investigate the association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer. Relevant published literatures were searched in PubMed, ProQuest, Web of Science and Medline databases during 1995–2016. Heterogeneity was evaluated by I2 statistic. Publication bias was tested by funnel plot and Egger’s test. Odds ratio and 95% CI were used to assess the association strength. The statistical analyses in this study were accomplished by STATA software package. A total of 40,609 cases of epithelial ovarian cancer and 368,452 controls in 38 publications were included. The result suggested that endometriosis was associated with an increased risk of epithelial ovarian cancer (OR = 1.42, 95% CI = 1.28–1.57), tubal ligation was associated with a decreased risk of epithelial ovarian cancer (OR = 0.70, 95% CI = 0.60–0.81), while hysterectomy show no relationship with epithelial ovarian cancer (OR = 0.97, 95% CI = 0.81–1.14). A stratified analysis showed there were associations between endometriosis and the increased risk of epithelial ovarian cancer for studies conducted in USA and Europe. Meanwhile, there were associations between tubal ligation and the decreased risk of epithelial ovarian cancer for studies conducted in USA, Asia, Europe and Australia. The result indicated that endometriosis was a risk factor of epithelial ovarian cancer whereas tubal ligation was a protective risk factor of epithelial ovarian cancer, hysterectomy may have no relationship with epithelial ovarian cancer. PMID:27854255

  15. Altered sensitivity to anti-endometriosis medicines in an adenomyosis patient with thyroid dysfunction.

    PubMed

    Tanaka, T; Umesaki, N; Ogita, S

    2000-10-01

    We report the rare case of a patient with adenomyosis who showed thyroid dysfunction of unknown etiology during treatment for endometriosis. She responded to nafarelin acetate and danazol when she was euthyroid but not to buserelin acetate when she was hyperthyroid. This suggests that the response to anti-endometriotic medicine in our patient was altered by impaired thyroid function and that this could occur in other such patients.

  16. Evaluation of antimullerian hormone levels before and after laparoscopic management of endometriosis

    PubMed Central

    Mostaejeran, Fatemeh; Hamoush, Zeinab; Rouholamin, Safoura

    2015-01-01

    Background: Serum antimullerian hormone (AMH) proposed to be a reliable marker of ovarian reserve; the aim of this study was to evaluate the influence and value of laparoscopic management in endometriosis as measured by serum AMH levels. Materials and Methods: In this cross-sectional study, 33 infertile patients who referred to fertility - Infertility Center of Isfahan - with different stages of endometriosis managed by diagnostic operative laparoscopy and serum AMH levels were measured pre and one month postoperative laparoscopy. Main outcome measures were serum AMH levels in correlation with the type of infertility, stage of endometriosis, and type of surgery in infertile patients. Results: 33 infertile patients enrolled in the study with mean age 28.9 ± 5 years, and thus did not show a significant difference. Mean serum AMH levels was 4.23 ± 3.75 ng/ml and 2.2 ± 2.47 ng/ml, respectively, in primary and secondary infertility groups before and one month after laparoscopy, which shows a significant difference (P < 0.001). Median AMH level changes in Cauterization (0.67 ± 0.76 ng/ml), endometrioma excision 2 ± 0.6 ng/ml, both 2.18 ± 0.81 ng/ml and shows no significant differences. Mean serum AMH levels were definitely decreased in minimal/mild and severe stage endometriosis before and 1 month after laparoscopy, (1.84 ± 2.06 ng/ml and 2.18 ± 3.45 ng/ml), respectively. Also serum AMH according to ovarian appearance and evolvement showed no significant differences after laparoscopy: (5.5 ± 1.4 ng/ml and 2.76 ± 0.96 ng/ml) and (3.37 ± 2.2 ng/ml and 1.84 ± 1.5 ng/ml). Conclusion: Serum AMH levels clearly decreased 1 month after operative laparoscopy. PMID:26605221

  17. Cystoscopy-assisted laparoscopy for bladder endometriosis: modified light-to-light technique for bladder preservation

    PubMed Central

    Stopiglia, Rafael Mamprin; Ferreira, Ubirajara; Faundes, Daniel Gustavo; Petta, Carlos Alberto

    2017-01-01

    ABSTRACT Introduction Endometriosis is a disease with causes still unclear, affecting approximately 15% of women of reproductive age, and in 1%-2% of whom it may involve the urinary tract. The bladder is the organ most frequently affected by endometriosis, observed around 85% of the cases. In such cases, the most effective treatment is partial cystectomy, especially via videolaparoscopy. Study Objective, Design, Size and Duration In order to identify and delimit the extent of the intravesical endometriosis lesion, to determine the resection limits, as well as to perform an optimal reconstruction of the organ aiming for its maximum preservation, we performed a cystoscopy simultaneously with the surgery, employing a modified light-to-light technique in 25 consecutive patients, from September 2006 to May 2012. Setting Study performed at Campinas Medical Center – Campinas – Sao Paulo – Brazil.Participants/materials, setting and methods: Patients aged 27 to 47 (average age: 33.4 years) with deep endometriosis with total bladder involvement were selected for the study. The technique used was conventional laparoscopy with a transvaginal uterine manipulator and simultaneous cystoscopy (the light-to-light technique). A partial videolaparoscopic cystectomy was performed with cystoscopy-assisted vesical reconstruction throughout the entire surgical time. The lesions had an average size of 2.75cm (ranging from 1.5 to 5.5cm). The average surgical time was 137.7 minutes, ranging from 110 to 180 minutes. Main Results Postoperative follow-up time was 32.4 months (12-78 months), with clinical evaluation and a control cystoscopy performed every six months. No relapse was observed during the follow-up period. Conclusions A cystoscopy-assisted partial laparoscopic cystectomy with a modified light-to-light technique is a method that provides adequate identification of the lesion limits, intra or extravesically. It also allows a safe reconstruction of the organ aiming for its

  18. Effects of Chinese Materia Medica-Fubao Danggui Jiao on experimental endometriosis.

    PubMed

    Sun, Xing; Chen, Lijue; Zeng, Fanbo

    2011-01-01

    The objective of this paper was to investigate the effects of a Chinese Materia Medica variant -Fubao Danggui Jiao (FDJ)-on experimental endometriosis. An endometriosis model was created by virtue of auto-transplantation of endometrial tissue onto rats' abdominal walls. The implants were allowed to grow for 30 days until the successful completion of the model. After that, forty endometriotic rats were randomly divided into four study groups and given different treatments: (1) negative control group (water, 2ml/kg, per os); (2) FDJ-A group (FDJ, 2ml/kg, per os); (3) FDJ-B group (FDJ, 4ml/kg, per os); (4) Danazol group (70mg/kg, per os). After 30 days with treatments, the volumes of endometriotic implants in each rat were measured. The implants and normal uterine horns were removed for routine histological examination. FDJ caused significant decreases in volumes of the surviving endometriotic implants, with two different doses having statistically equivalent effects. Upon histological examination, FDJ was observed to cause regression of epithelium and stroma of endometriotic implants. FDJ had revealed promising therapeutic effects on endometriosis.

  19. The etiquette of endometriosis: stigmatisation, menstrual concealment and the diagnostic delay.

    PubMed

    Seear, Kate

    2009-10-01

    Endometriosis is a chronic gynaecological condition of uncertain aetiology characterised by menstrual irregularities. Several studies have previously identified a lengthy delay experienced by patients between the first onset of symptoms and eventual diagnosis. Various explanations have been advanced for the diagnostic delay, with both doctors and women being implicated. Such explanations include that doctors normalise women's menstrual pain and that women might delay in seeking medical advice because they have difficulty distinguishing between 'normal' and 'abnormal' menstruation. It has been suggested that the diagnostic delay could be reduced if women were trained in how to distinguish between 'normal' and 'abnormal' menstrual cycles. In this paper I argue that whilst these may be factors in the diagnostic delay, women's reluctance to disclose problems associated with their menstrual cycle may be a more significant and hitherto neglected factor. I argue women are reluctant to disclose menstrual irregularities because menstruation is a 'discrediting attribute' (Goffman, 1963) and disclosure renders women vulnerable to stigmatisation. Women actively conceal their menstrual irregularities through practices of the 'menstrual etiquette' (Laws, 1990) which involves the strategic concealment of menstrual problems. This argument is supported through an analysis of the experiences of 20 Australian women diagnosed with endometriosis. The ramifications of this analysis for chronic pain conditions more generally and for practical strategies designed to address the endometriosis diagnostic delay are considered.

  20. Differences in characteristics among 1,000 women with endometriosis based on extent of disease

    PubMed Central

    Sinaii, Ninet; Plumb, Katherine; Cotton, Louise; Lambert, Ann; Kennedy, Stephen; Zondervan, Krina; Stratton, Pamela

    2010-01-01

    Objective To determine the relationship between disease severity and patient characteristics in endometriosis. Design Cross-sectional study of self-reported survey data. Setting Academic research setting. Patient(s) One thousand women in the Oxford Endometriosis Gene (OXEGENE) study. Intervention(s) None. Main Outcome Measure(s) Participants were assigned to one of two groups with predominantly revised AFS stage I–II (group I, n = 423) or III–IV disease (group II, n = 517). Their characteristics were compared by disease extent. Result(s) Most participants were white (96%) and of reproductive age (81%). Women in group I were significantly younger on entering the study (39.9 ± 0.5 vs. 44.5 ± 0.4 years). Overall time to diagnosis did not differ between groups. The most common symptoms leading to a diagnosis were dysmenorrhea (79%) and pelvic pain (69%). In group II, subfertility (21.5% vs. 30.0%) and an ovarian mass (7.3% vs. 29.4%) more commonly led to a diagnosis, whereas dyspareunia (51.1% vs. 39.5%) was significantly more common in group I. Subfertility (41.5% vs. 53.4%) remained more common in group II throughout reproductive life, although birth and miscarriage rates were similar. Conclusion(s) Pelvic pain is common to all with endometriosis and those with more extensive disease report higher rates of subfertility. Remarkably, the time to diagnosis was similar among women. PMID:17498711

  1. Human Footprints in Relation to the 1790 Eruption of Kilauea

    NASA Astrophysics Data System (ADS)

    Swanson, D. A.; Rausch, J.

    2008-12-01

    In 1790, a party of warriors and their families was decimated by an explosive eruption of Kilauea; fatality estimates range from about 80 to 5,405. In 1920, thousands of footprints made by barefoot walkers in wet accretionary lapilli ash were found within a few kilometers southwest of Kilauea's summit. In 1921, Jaggar related the footprints to survivors or rescuers of the 1790 eruption, mainly because he assumed that few people visited the supposedly forbidden area except in 1790. Archaeologists from Hawai'i Volcanoes National Park recently questioned whether the footprints were made at that time and by warriors, citing a wide range of directions that people were walking and evidence of extensive human use of the area. Forensic and anthropologic studies indicate that a human foot is about 15 percent of an individual's height. A man's foot may be slightly more that 15 percent, a women's slightly less, but nonetheless the height can be estimated to within a few centimeters. We measured the heel-big toe length of more than 400 footprints and calculated an average height of 1.5 m, including some children only a little more than 1 m tall. Few calculated heights are 1.75 m or more. Early Europeans described Hawaiian warriors as tall, one missionary estimating an average height of 1.78 m. A footprint may be larger than a foot, particularly in slippery, wet ash, so our estimates of heights are probably somewhat too large. The data indicate that most of the footprints were made by women and children, not by men, much less warriors. We traced the footprint-bearing ash into the tephra section on the southwest side of Kilauea's caldera. It occurs high in the section, resting on older explosive deposits. Its surface is indented by small lithic lapilli, which fell into the ash while it was still wet; a few even landed in footprints. The lithic lapilli are at the edge of a thick block and lapilli deposit that fell from a high eruption column; the column reached well into the jet

  2. Bioethics & human rights: access to health-related goods.

    PubMed

    Arras, John D; Fenton, Elizabeth M

    2009-01-01

    There are many good reasons for a merger between bioethics and human rights. First, though, significant philosophical groundwork must be done to clarify what a human right to health would be and--if we accept that it exists--exactly how it might influence the practical decisions we face about who gets what in very different contexts.

  3. The relations between neuroscience and human behavioral science.

    PubMed Central

    Strumwasser, F

    1994-01-01

    Neuroscience seeks to understand how the human brain, perhaps the most complex electrochemical machine in the universe, works, in terms of molecules, membranes, cells and cell assemblies, development, plasticity, learning, memory, cognition, and behavior. The human behavioral sciences, in particular psychiatry and clinical psychology, deal with disorders of human behavior and mentation. The gap between neuroscience and the human behavioral sciences is still large. However, some major advances in neuroscience over the last two decades have diminished the span. This article reviews the major advances of neuroscience in six areas with relevance to the behavioral sciences: (a) evolution of the nervous system; (b) visualizing activity in the human brain; (c) plasticity of the cerebral cortex; (d) receptors, ion channels, and second/third messengers; (e) molecular genetic approaches; and (f) understanding integrative systems with networks and circadian clocks as examples. PMID:7513347

  4. Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options

    PubMed Central

    Trovato, Maria Antonietta; Palmara, Vittorio Italo; Rapisarda, Agnese Maria Chiara; Sturlese, Emanuele; De Dominici, Rosanna; Alecci, Stefano; D'Amico, Paolo; Triolo, Onofrio

    2016-01-01

    Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes. PMID:27579309

  5. Extracts of Salvia miltiorrhiza Bunge on the cytokines of rat endometriosis models.

    PubMed

    Zhou, Zan-Hua; Weng, Qing; Zhou, Jian-Hong; Zhou, Jue

    2012-01-01

    Endometriosis is a common mysterious and fascinating gynaecological condition with diverse clinical manifestations, highly variable and unpredictable clinical course with decreased quality of life. Clinically, Salvia miltiorrhiza Bunge (SMB, Chinese Danshen) has been applied to treat endometriosis and get satisfactory results. The present study was aimed to explore the effects of the extracts of SMB (ESMB) on the serum levels of cancer antigen 125 (CA-125) and the levels of interleukin (IL)-13, IL-18 and tumor necrosis factor-alpha (TNF-alpha) in the peritoneal fluids of rat endometriosis models. Three extraction methods for SMB were compared, which are the sample extracted with conventional method, the sample extracted with espresso coffee machine and the commercial condensed powder of natural products. We determined tanshinone IIA, salvianolic acid B and danshensu in the ESMB of different extraction methods. Forty female Sprague-Dawley (SD) rats were randomly divided into ESMB group, Danazol (positive control) group, model group and the sham-operation group (Sham group). After all the treatment ended, the serum levels of CA125 and the levels of IL-13, IL-18 and TNF-alpha in the peritoneal fluids of rat endometriosis models were measured using enzyme-linked immune-sorbent assay (ELISA) as directed by the manufacturer. The extraction efficiency of the ESMB samples extracted with coffee machine ranged from 600µm to 710µm was the highest. The serum levels of CA-125 and the levels of IL-18 and TNF-alpha in the peritoneal fluids of ESMB group, Danazol group and Sham group were significantly lower than those of the Model group (P<0.05). The serum levels of CA-125 and the levels of IL-18 and TNF-alpha in the peritoneal fluids of Danazol group and ESMB group were significantly higher than those of Sham group, respectively (P<0.05), and no marked difference existed between them (P>0.05). The levels of IL-13 in the peritoneal fluids of ESMB group, Danazol group and Sham

  6. Auditory and Vestibular Issues Related to Human Spaceflight

    NASA Technical Reports Server (NTRS)

    Danielson, Richard W.; Wood, Scott J.

    2009-01-01

    Human spaceflight provides unique opportunities to study human vestibular and auditory systems. This session will discuss 1) vestibular adaptive processes reflected by pronounced perceptual and motor coordination problems during, and after, space missions; 2) vestibular diagnostic and rehabilitative techniques (used to promote recovery after living in altered gravity environments) that may be relevant to treatment of vestibular disorders on earth; and 3) unique acoustical challenges to hearing loss prevention and crew performance during spaceflight missions.

  7. The Laboratory Rat: Relating Its Age With Human's

    PubMed Central

    Sengupta, Pallav

    2013-01-01

    By late 18th or early 19th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years). Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor. PMID:23930179

  8. Praxis and Pedagogy as Related to the Arts and Humanities

    ERIC Educational Resources Information Center

    Mulcahy, D. G.

    2010-01-01

    Based on a review of its historical evolution and the contributions of significant writers in the field, this article addresses perennial questions of purpose, content and pedagogy in education in the arts and humanities and, more broadly, liberal education. Taking cognizance of the educational significance of service-learning and practical…

  9. A Relational Hermeneutical Approach to Human Rights Education

    ERIC Educational Resources Information Center

    Al-Daraweesh, Fuad

    2010-01-01

    This research is an effort to transcend the debate of universalism and cultural relativism by offering a new conceptualization of human rights. The conceptualization is presented through the development of a theoretical framework in the form of an epistemology. The research articulates and defends the epistemology, which is grounded on…

  10. Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model.

    PubMed

    Li, Yanfen; Adur, Malavika K; Kannan, Athilakshmi; Davila, Juanmahel; Zhao, Yuechao; Nowak, Romana A; Bagchi, Milan K; Bagchi, Indrani C; Li, Quanxi

    2016-01-01

    Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.

  11. Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model

    PubMed Central

    Kannan, Athilakshmi; Davila, Juanmahel; Zhao, Yuechao; Nowak, Romana A.; Bagchi, Milan K.; Bagchi, Indrani C.; Li, Quanxi

    2016-01-01

    Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis. PMID:27776183

  12. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

    PubMed

    Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W

    2014-02-01

    In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  13. The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis.

    PubMed

    Agostinis, C; Zorzet, S; De Leo, R; Zauli, G; De Seta, F; Bulla, R

    2015-01-01

    To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.

  14. The Combination of N-Acetyl Cysteine, Alpha-Lipoic Acid, and Bromelain Shows High Anti-Inflammatory Properties in Novel In Vivo and In Vitro Models of Endometriosis

    PubMed Central

    Agostinis, C.; Zorzet, S.; De Leo, R.; Zauli, G.; De Seta, F.; Bulla, R.

    2015-01-01

    To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory “marker” VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis. PMID:25960622

  15. Human papillomavirus and human immunodeficiency virus infections: relation with cervical dysplasia-neoplasia in African women.

    PubMed

    La Ruche, G; You, B; Mensah-Ado, I; Bergeron, C; Montcho, C; Ramon, R; Touré-Coulibaly, K; Welffens-Ekra, C; Dabis, F; Orth, G

    1998-05-18

    Our study assessed the factors associated with cervical squamous intra-epithelial lesions (SILs) and invasive cervical cancer, with special attention to human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. Women from 3 outpatient gynecology clinics of Abidjan, Côte d'Ivoire, were screened for cervical abnormalities: 151 women with low-grade SILs and 151 controls, 60 with high-grade SILs and 240 controls, and 13 with invasive cancer and 65 controls were enrolled in 3 case-control studies. Controls were chosen at random among the women without lesions, with a frequency matching for age and center. We used the PCR method for the detection of cervical HPV DNA and the restriction fragment length polymorphism analysis for HPV typing. HIV antibody testing and CD4 cell count were performed. In multivariate analyses, factors associated with cervical lesions were: for low-grade SILs, HPV positivity, HIV-1 seropositivity and parity >3; for high-grade SILs, HPV positivity, chewing tobacco, HIV-1 seropositivity and illiteracy, and for invasive cancer, HPV positivity only. We found a diversity of HPV types associated with SILs. In HIV-1-infected women, SILs occurred at an early stage of HIV disease. Women infected with both HIV-1 and HPV were at much higher risk of SILs than women infected with each of these 2 viruses separately. Invasive cancer was linked to HIV-2 infection in univariate analysis only. Our results suggest that the relation of SILs with HIV-1 infection is mainly explained by HPV infection and that HIV-1-infected African women may not often reach the invasive stage of cervical cancer.

  16. Spontaneous Healing of a Rectovaginal Fistula Developing after Laparoscopic Segmental Bowel Resection for Intestinal Deep Infiltrating Endometriosis

    PubMed Central

    Trippia, Carlos Henrique; Zomer, Monica Tessmann

    2013-01-01

    The surgical treatment of intestinal deep infiltrating endometriosis has an associated risk of major complications such as dehiscence of the intestinal anastomosis, pelvic abscess, and rectovaginal fistula. The management of postoperative rectovaginal fistula frequently requires a reoperation and the construction of a stoma for temporary fecal diversion. In this paper we describe a 27-year-old woman undergoing laparoscopic treatment of deep infiltrating endometriosis (extramucosal cystectomy, resection of the uterosacral ligaments, resection of the posterior vaginal fornix, and segmental bowel resection) complicated by a rectova