Am J Reprod Immunol. 2011 Aug 23. doi: 10.1111/j.1600-0897.2011.01063.x. [Epub ahead of print]

Modulation of Hepatocyte Growth Factor Secretion in Human Female Reproductive Tract Stromal Fibroblasts by Poly (I:C) and Estradiol.

Coleman KD, Ghosh M, Crist SG, Wright JA, Rossoll RM, Wira CR, Fahey JV.

Source

Physiology Department, Dartmouth Medical School, Lebanon, NH, USA.

Abstract

Citation Coleman KD, Ghosh M, Crist SG, Wright JA, Rossoll RM, Wira CR, Fahey JV. Modulation of Hepatocyte Growth Factor Secretion in Human Female Reproductive Tract Stromal Fibroblasts by Poly (I:C) and Estradiol. Am J Reprod Immunol 2011

PROBLEM:

Hepatocyte Growth Factor (HGF) secretion facilitates epithelial cell growth and development in the female reproductive tract (FRT) and may contribute to pathological conditions such as cancer and endometriosis. We hypothesized that estradiol and poly (I:C), a synthetic RNA mimic, may have a regulatory effect on HGF secretion by stromal fibroblasts from FRT tissues.

METHOD OF STUDY:

Following hysterectomies, normal tissue from the uterus, endocervix, and ectocervix were dispersed into stromal cell fractions by enzymatic digestion and differential filtering. Stromal fibroblasts were cultured and treated with estradiol and/or poly (I:C), and conditioned media were analyzed for HGF via enzyme-linked immunosorbent assay.

RESULTS:

Treating uterine fibroblasts with estradiol or poly (I:C) significantly increased HGF secretion. When uterine fibroblasts were co-treated with estradiol and poly (I:C), the effect on HGF secretion was additive. In contrast, stromal fibroblasts from endo- and ecto-cervix were unresponsive to estradiol, but were stimulated to secrete HGF by poly (I:C).

CONCLUSION:

HGF secretion is uniquely regulated in the uterus, but not in ecto- and endo-cervix, by estradiol. Moreover, potential viral pathogens further induce HGF. These findings have potential applications in understanding both hormonal regulation of normal tissue as well as the role of HGF in tumorogenesis, endometriosis, and human immunodeficiency virus infection.

© 2011 John Wiley & Sons A/S.

Scand J Immunol. 2011 Aug 26. doi: 10.1111/j.1365-3083.2011.02616.x. [Epub ahead of print]

Promoter -817C>T variant of B Lymphocyte Stimulator gene -BLyS, and susceptibility to endometriosis-related infertility and idiopathic infertility in Brazilian population.

Christofolini DM, Cavalheiro CM, Teles JS, Lerner TG, Brandes A, Bianco B, Barbosa CP.

Source

Division of Human Reproduction and Genetics – Department of Gynecology and Obstetrics – Faculdade de Medicina do ABC – Santo André/SP, Brazil.

Abstract

 Many theories have been proposed to explain the development of Background/Aim: endometriosis and recently, autoimmune etiology has been suggested. Besides, it is well know that endometriosis, especially the advanced disease, may impair fertility. B lymphocyte stimulator (BLyS) is a cytokine produced by macrophages necessary for normal B cell development. One of the most studied polymorphisms is the -817C/T in the promoter region of the gene. We aimed to assess the association between endometriosis-related infertility and idiopathic infertility and the BLyS -817C/T  We performed a polymorphism in a Brazilian population. Methods: case-control study comprising 165 infertile women with endometriosis, 83 with idiopathic infertility and 145 fertile, and assessed the association with BLys -817C/T polymorphism. Detection of BLyS -817C/T polymorphism was performed by TaqMan PCR. The results were analyzed statistically and a p-value < 0.05 was considered significant.  The results disclosed similar genotype and allelic Results: frequencies between endometriosis-related infertility and control group (p=0.225), regardless the disease stage (p=0.213 and p=0.462, respectively). However, a statistically significant difference was observed regarding idiopathic infertile group compared to controls (p=0.048). Considering the dominant and recessive inheritance models, no significant differences in both endometriosis and idiopathic infertility group were found. The genotype frequencies  were in Hardy-Weinberg equilibrium in all studied groups. Conclusions: The results point to a possible association between BLyS -817C/T polymorphism and idiopathic infertility in Brazilian population.

Yakugaku Zasshi. 2011;131(9):1271-87.

Drug Discovery by Formulation Design and Innovative Drug Delivery Systems (DDS).

Okada H.

Source

Tokyo University of Pharmacy & Life Sciences.

Abstract

  This review describes studies on drug discovery using a rational formulation design and innovative, drug delivery systems (DDS) for biomaterials such as therapeutic peptides and nucleotides. The microcapsules of the LH-RH superagonist leuprorelin acetate prepared using the new in-water drying method and biodegradable polymers, such as PLGA and PLA, could achieve a long-term sustained release for 1-6 months thereby facilitating easily treatment of hormone-dependent diseases, prostate cancer, endometriosis, and precocious puberty. This DDS technology showed an improvement in patient QOL and highly promoted the clinical value of the agonist. Moreover, PLGA microcapsules of siRNAs against VEGF, cFLIP, Raf-1, and Int6 have also been developed to treat various cancers and arteriosclerosis obliterans. To develop therapeutic nucleotides, a particle design is created using functional peptides, such as cell penetrating peptides (CPP), nuclear localizing signals (NLS), tight junction reversible openers (AT1002), bombesin, and dynein light chain-associated sequences. siRNA use should lead to a paradigm shift in drug discovery against various diseases. Tat analog with NLS could enhance the potency of a vaginal DNA vaccine. The artificial Tat CPP of STR-CH(2)R(4)H(2)C synthesized in our laboratory could efficiently deliver siRNAs into many types of cells and enhance the therapeutic effects for treating sarcoma, atopic dermatitis, allergic rhinitis, and asthma by intratumor injection and inhalation of the nanoparticles. Tat and AT1002 analogs used to treat atopic dermatitis in mice increased cell membrane permeability to siRelA, a siRNA against a subclass of NF-κB, and exhibited striking therapeutic and preventive effects.

Atherosclerosis. 2011 Aug 10. [Epub ahead of print]

Increased asymmetric dimethylarginine and enhanced inflammation are associated with impaired vascular reactivity in women with endometriosis.

Kinugasa S, Shinohara K, Wakatsuki A.

Source

Department of Obstetrics and Gynecology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.

Abstract

OBJECTIVE:

Enhanced inflammatory responses which may inhibit vascular reactivity, are associated with endometriosis development. Asymmetric dimethylarginine (ADMA), an inhibitor of endogenous nitric oxide synthase, is also implicated in endothelial dysfunction. We aimed to determine whether plasma ADMA and systemic inflammation are associated with endothelial function in women with endometriosis.

METHODS:

We evaluated 41 women with and 28 women without endometriosis. Plasma levels of lipids and inflammatory markers such as high sensitive-C reactive protein (hs-CRP), serum amyloid protein A (SAA), and interleukin-6 (IL-6) were measured in the two groups. We also measured levels of ADMA and symmetric dimethylarginine (SDMA). High-resolution ultrasonography measured flow-mediated vasodilation (FMD) to assess vasodilatory responses.

RESULTS:

FMD was significantly lower in women with endometriosis compared to those without endometriosis (8.39±0.43% vs 10.79±0.54%, P=0.001). While plasma lipid levels did not differ significantly between groups, levels of AMDA, but not SDMA, were significantly higher in women with endometriosis (409.7±10.1pmol/L vs 383.0±48.3pmol/L, P=0.04). Inflammatory markers were also significantly higher in these women (hs-CRP: 1053.3±252.0ng/mL vs 272.0±83.3ng/mL, P=0.02; SAA: 8.00±1.53μg/mL vs 3.82±0.42μg/mL, P=0.04; IL-6: 2.73±0.75pg/mL vs 1.05±0.60pg/mL, P=0.04). FMD was negatively correlated with plasma levels of ADMA (r=-0.37, P=0.01) and log hs-CRP (r=-0.34, P=0.01).

CONCLUSION:

Increased plasma ADMA levels and enhanced inflammation are associated with inhibited endothelial function in women with endometriosis.

Fertil Steril. 2011 Sep;96(3):711-714.e1.

Prevalence of uterine leiomyomas in lymphangioleiomyomatosis.

Taveira-Dasilva AM, Rabel A, Gochuico BR, Avila NA, Moss J.

Source

Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Abstract

OBJECTIVE:

To determine the frequency of uterine leiomyomas and hysterectomy in patients with lymphangioleiomyomatosis (LAM), a disease characterized by proliferation of abnormal-appearing smooth muscle-like cells.

DESIGN:

Retrospective study.

SETTING:

Natural history study at the National Institutes of Health.

PATIENT(S):

456 patients with sporadic LAM and LAM associated with tuberous sclerosis complex (LAM/TSC).

INTERVENTION(S):

Review of records and pelvic computed axial tomography scans.

MAIN OUTCOME MEASURE(S):

Prevalence of uterine leiomyomas and hysterectomy.

RESULT(S):

A total of 174 women had uterine leiomyomas (38%). One hundred eighteen were diagnosed by computed tomographic scan and 56 were diagnosed by hysterectomy. Among 323 patients who did not have hysterectomy, 105 of 270 patients (39%) with sporadic LAM and 13 of 53 (25%) with LAM/TSC had uterine leiomyomas. Hysterectomy was performed in 108 of 378 subjects with sporadic LAM and 25 of 78 with LAM/TSC. Fifty-six patients were found to have uterine fibroids on hysterectomy. The most common indications for hysterectomy were uterine leiomyoma, LAM, and endometriosis.

CONCLUSION(S):

Uterine leiomyomas are not more common in LAM than in the general population. However, in LAM, the frequency of hysterectomy is higher because of it having been recommended for treatment of LAM.

Published by Elsevier Inc.

Fertil Steril. 2011 Sep;96(3):692-6.

Lymphatic spread of endometriosis to pelvic sentinel lymph nodes: a prospective clinical study.

Tempfer CB, Wenzl R, Horvat R, Grimm C, Polterauer S, Buerkle B, Reinthaller A, Huber JC.

Source

Department of Obstetrics and Gynecology, Ruhr University of Bochum, Bochum, Germany.

Abstract

OBJECTIVE:

To establish the prevalence of endometriosis metastatic to pelvic sentinel lymph nodes (PSLN) in women with ovarian and/or peritoneal endometriosis.

DESIGN:

Prospective clinical study.

SETTING:

Academic research institution.

PATIENT(S):

Women with a laparoscopic diagnosis of ovarian and/or peritoneal endometriosis verified by intraoperative frozen section analysis.

INTERVENTION(S):

Resection of endometriotic lesions and PSLN after cervical blue dye injection.

MAIN OUTCOME MEASURE(S):

Histologic analysis of PSLN for the presence of endometriosis and immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK), and CD-10 expression.

RESULT(S):

The study enrolled 26 women with suspected endometriosis; endometriosis was confirmed in 23 women, and a PSLN was identified in 19 women. A total of 37 (right side: 20; left side: 17) lymph nodes were removed. The prevalence of endometriotic lesions in PSLN was 11% (2 of 19). Both lesions were positive for ER, PR, CK, and CD-10. Isolated endometriotic-like cells (IELCs) staining positive for ER and PR were identified in the peripheral sinus of 16 (80%) of 20 and 14 (70%) of 20 PSLN, respectively. All IELCs lacked CK staining, whereas CD-10 staining was present in 16 (80%) of 20 cases, indicating a stromal origin of IELCs. Intraoperative and/or postoperative complications were observed in 1 (5%) of 19 women.

CONCLUSION(S):

Spread of IELCs to PSLN is common in ovarian and/or peritoneal endometriosis. Metastatic lesions in PSLN are present in 11% of women. Further studies to evaluate the prognostic and predictive value of endometriotic spread to PSLN are warranted.

Fertil Steril. 2011 Sep;96(3):522-9.

Assessment of endometrial receptivity.

Lessey BA.

Source

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University Medical Group, Greenville Hospital System, Greenville, South Carolina.

Abstract

OBJECTIVE:

To provide a focused review of the scientific literature pertaining to endometrial receptivity.

DESIGN:

Review of the literature and appraisal of relevant articles.

SETTING:

Academic teaching hospital.

PATIENT(S):

Women with infertility.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Critical review of the literature.

RESULT(S):

Although a consensus has been achieved regarding the existence of a temporally defined period during which embryo attachment and invasion can occur (called the “window of implantation”), reliable methods to assess “receptivity” have not been established or adequately validated. In women with certain gynecologic disorders, including endometriosis, tubal disease, and polycystic ovary syndrome, endometrial receptivity seems to be compromised, leading to infertility and pregnancy loss. The establishment of reliable biomarkers for the detection of defects in endometrial receptivity has been a long-sought goal that remains an elusive target. The validation of endometrial biomarkers will require properly designed and implemented studies based on the recognition that endometrial receptivity defects are not equally distributed in women with endometriosis or these other conditions.

CONCLUSION(S):

Rapidly advancing technologies are bringing new biomarkers to the clinical arena that promise to further reveal the complexities of the implantation process.

 

Womens Health (Lond Engl). 2011 Sep;7(5):585-90.

Management of endometriosis-related pain: an update.

Luciano DE, Luciano AA.

Source

Center for Fertility and Women’s Health, 100 Grand Street Suite E3, New Britain, CT 06050, USA. aluciano@thocc.org.

Abstract

Endometriosis is a chronic and recurrent condition affecting 6-10% of women of a reproductive age. It results from implantation of endometrial tissue outside the uterine cavity. It is associated with pelvic pain and infertility. Treatment for endometriosis ranges from medical management, to conservative surgery, to definitive surgery with a hysterectomy and bilateral salpingo-oophorectomy, and should be based on patient’s fertility desires and tolerance. Medical treatment involves hormonal manipulation to induce a hypoestrogenic or antiestrogenic state to induce regression and apoptosis of lesions. Endometriosis can have dire effects on women’s lives and productivity; this article will focus on early diagnosis, treatment and prevention of recurrence of the disease.

J Pediatr Adolesc Gynecol. 2011 Oct;24(5 Suppl):S7-12.

Markers of adult endometriosis detectable in adolescence.

Chapron C, Borghese B, Streuli I, de Ziegler D.

Source

Université Paris Descartes-Assistance Publique Hôpitaux de Paris, CHU Cochin, Department of Ob Gyn and Reproductive Medicine, Paris, France.

Abstract

Endometriosis, a disease of young females that is possibly a devastating ailment requiring surgery, appears to be associated with certain features encountered in adolescence. First among these symptoms is the history of severe and lasting dysmenorrhea at the time of adolescence and the need to use oral contraceptives (OCs) for alleviating dysmenorrhea that failed to respond to nonsteroidal anti-inflammatory drugs (NSAIDs). Further awareness about existing associations between certain symptoms experienced at adolescence and the later development of endometriosis is important. Indeed, the possibility of diagnosing endometriosis earlier when suggested by clinical history could lead to less extensive surgery and thus, less damage. Experimental verification of this insight, however, is needed before the concept that early diagnosis means lesser destructive surgery can be ascertained.

J Pediatr Adolesc Gynecol. 2011 Oct;24(5 Suppl):S2-6.

Treating endometriosis in adolescents: does it matter?

Ballweg ML.

Source

Endometriosis Association, Milwaukee, WI 53223, USA. MaryLou@EndometriosisAssn.org

Abstract

Endometriosis has major physical and psychosocial impacts on teens, as well as long-term implications for their health. The hidden suffering of millions of adolescents worldwide calls on the medical profession to respond, despite the challenges. Given the increasing understanding of adolescent endometriosis, treating adolescents with endometriosis can be a most rewarding experience. Moreover, diagnosing and treating the disease early could prevent more complicated disease later, as well as comorbidities. Helping these girls may save them, their families, and their communities much physical and emotional pain, as well as lessen the huge burden on our health care systems and society.

J Pediatr Adolesc Gynecol. 2011 Oct;24(5 Suppl):S18-9.

Scientific investigation of endometriosis among adolescents.

Shah DK, Missmer SA.

Source

Division of Reproductive Medicine, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.

Abstract

The scientific literature on endometriosis specific to the adolescent population is limited, and the existing data are retrospective and descriptive in nature. It is possible that the disease has a different pathophysiology in adolescents, but little epidemiologic or molecular data exist to support or refute this speculation. In addition, the limited literature does not yet confirm that intervening in the adolescent population prevents long-term sequelae such as pain and infertility as adults. Case-control and cohort studies to identify risk factors, as well as prospective observational and intervention studies to assess treatment outcome, are required to further knowledge about endometriosis in the adolescent population. The scientific literature on endometriosis specific to the adolescent population is limited, and the existing data are retrospective and descriptive in nature. This review summarizes studies that have been done to date and suggests areas for future investigation.

J Pediatr Adolesc Gynecol. 2011 Oct;24(5 Suppl):S13-7.

Helping “adult gynecologists” diagnose and treat adolescent endometriosis: reflections on my 20 years of personal experience.

Laufer MR.

Source

Division of Gynecology, Children’s Hospital Boston, Boston, MA, USA. marc.laufer@childrens.harvard.edu

J Pediatr Adolesc Gynecol. 2011 Oct;24(5 Suppl):S1.

Adolescent endometriosis: improving the comfort level of health care providers treating adolescents with endometriosis.

Ballweg ML, Laufer MR.

 

Rev Assoc Med Bras. 2011 Aug;57(4):456-461.

Environmental factors and endometriosis.

[Article in English, Portuguese]

Bellelis P, Podgaec S, Abrão MS.

Source

Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP.

Abstract

Endometriosis represents a common gynecological condition affecting 5%-15% of childbearing age women and up to 3% 5% of post-menopausal women. This disease is defined by the presence of stromal and/or endometrial glandular epithelium implants in extra-uterine locations possibly compromising several sites. Humans and animals are daily exposed to chemical pollutants that could adversely influence physiological processes and potentially cause diseases, including endometriosis. In this review, the authors aimed at settling the influence of environmental and dietary factors on endometriosis pathogenesis. The mechanism by which dioxin and its similes (TCDD/PCBs) act changing the endometrial physiology remains uncertain and is speculative due to the difficulty in assessing the exposure over intrauterine life, childhood and adulthood and its actual consequences, in addition to the limitations to its in vitro reproducibility. We need to better understand the mechanism of action of these environmental pollutants, not only on reproductive health, but also on overall health of individuals and so prevention strategies, including not only population education, but setting exposure limits, less polluting techniques and a better use of our natural resources, could be promoted.

Mol Cell Endocrinol. 2011 Aug 22. [Epub ahead of print]

Estrogen biosynthesis and signaling in endometriosis.

Huhtinen K, Ståhle M, Perheentupa A, Poutanen M.

Source

Department of Physiology, Institute of Biomedicine, University of Turku, 20014 Turku, Finland; Department of Obstetrics & Gynecology, Turku University Hospital, 20520 Turku, Finland.

Abstract

Endometriosis is an estrogen-dependent gynecological disease where endometrium-like tissue grows outside uterine cavity. Endometriotic cell proliferation is stimulated by estrogens acting predominantly via their nuclear receptors. Estrogen receptors (ESR1, ESR2) are ligand activated transcription factors whose activation is dependent on the cell-specific dynamic expression of the receptors, on the interacting proteins and on the ligand availability. The different types of endometriotic lesions, peritoneal, deep, and ovarian endometriosis, may respond to estrogens differentially due to differences in the expression of the receptors and interacting proteins, and due to potential differences in the ligand availability regulated by the local estrogen synthesis. This review summarizes the current knowledge of estrogen synthesizing enzymes and estrogen receptors in different types of endometriosis lesions. Further studies are still needed to define the possible differences in steroid metabolism in different types of endometriotic lesions.

 

J Pediatr Adolesc Gynecol. 2011 Oct;24(5):233.

Endometriosis in adolescents: a whole different focus.

Sanfilippo JS.

 

J Minim Invasive Gynecol. 2011 Sep-Oct;18(5):666-7.

The singer, not the song.

Muzii L, Miller CE.

Source

Department of Obstetrics and Gynecology, Università Campus BioMedico, Rome, Italy.

Abstract

Recently, data have been published on the possible damage to the healthy ovarian tissue determined by surgery for the excision of endometriomas. We believe that, besides endometriosis in itself, the overall quality of surgery may have a major role in determining damage to the ovary. In recent years, surgeons dedicated to the treatment of endometriosis have refined the technique of laparoscopic surgery for the excision of endometriomas, with particular attention in developing the correct plane of cleavage and in the judicious use of electrosurgery. Quality of the surgery, and not surgery per se, may be important. Surgery is the gold standard treatment for ovarian endometriomas, but it should be performed with proper techniques by specifically trained surgeons. It’s the singer, not the song.

Gut. 2011 Aug 25. [Epub ahead of print]

Visceral hypersensitivity in endometriosis: a new target for treatment?

Issa B, Onon TS, Agrawal A, Shekhar C, Morris J, Hamdy S, Whorwell PJ.

Source

University of Manchester, Manchester, UK.

Abstract

ObjectiveIn women presenting to gynaecological clinics with lower abdominal pain, the cause is frequently attributed to endometriosis irrespective of whether it is found to be minimal or extensive at laparoscopy. Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis.MethodsVisceral sensitivity to balloon distension, symptoms and psychological status were assessed following laparoscopy in 20 women with minimal to mild endometriosis, 20 with moderate to severe endometriosis, 20 with laparoscopy negative abdominal pain and 20 asymptomatic women undergoing laparoscopic sterilisation who acted as controls, and compared with 20 women with IBS.ResultsCompared with controls, patients with minimal to mild and moderate to severe endometriosis had a higher prevalence of symptoms consistent with IBS (0% vs 65% and 50%, respectively, p<0.001) with significantly lower mean pain Hg (95% CI 24.5 Hg (95% CI 36.0 to 43.0) vs 28.1 mm thresholds (39.5 mm Hg (95% CI 24.9 to 32.6), p=0.002) not to 31.6), p=0.001 and 28.8 mm explained by differences in rectal compliance. Patients with laparoscopy negative pain had symptoms and visceral sensitivity similar to patients with IBS. Controls undergoing laparoscopy had normal sensitivity, indicating that the laparoscopic procedure was not inducing hypersensitivity.ConclusionVisceral hypersensitivity is extremely common in endometriosis and could be intensifying the pain. This finding might explain why mildly affected individuals often complain of severe symptoms out of proportion to the extent of their disease. This study has introduced a completely new concept into the understanding of pain in endometriosis and could open up new opportunities for treatment.

Hum Reprod. 2011 Aug 24. [Epub ahead of print]

Ovarian surgery for bilateral endometriomas influences age at menopause.

Coccia ME, Rizzello F, Mariani G, Bulletti C, Palagiano A, Scarselli G.

Source

Department of Science for the Health of Woman and Child, University of Florence, Via Ippolito Nievo 2, 50129 Florence, Italy.

Abstract

BACKGROUNDQuestions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function. To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure.METHODSIn a tertiary university Clinic, longitudinal prospective cohort study. Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study. A prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution of menstrual pattern, symptoms and reproductive outcomes were investigated.RESULTSFrom over the 14-year period, 302 patients were included in the study. The mean age (±SD) of patients was 32.6 ± 5.6 years; the median duration of follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women (14.3%) at a mean age of 45.3 ± 4.3 years (range 32-52 years). Women previously submitted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma (42.1 ± 5.1 years versus 47.1 ± 3.5 years, P = 0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%) menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas (R(2) = 0.754, P = 0.002).CONCLUSIONSPatients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.

Hum Immunol. 2011 Aug 10. [Epub ahead of print]

Comparison of KIR gene content profiles revealed a difference between northern and southern Persians in the distribution of KIR2DS5 and its linked loci.

Solgi G, Ghafari H, Ashouri E, Alimoghdam K, Rajalingam R, Amirzargar A.

Source

Immunology Department, Medical School, Ahvaz University of Medical Sciences, Ahvaz, Iran.

Abstract

Killer cell immunoglobulin-like receptors (KIR) are the key receptors of human natural killer (NK) cells that mount an early immune response against infection and tumors. The number and type of KIR genes are substantially variable between individuals and populations. Recently we reported KIR gene content diversity in a Persian population living in the southern province of Fars, which is comparable to that of European Caucasians. These results are consistent with the ethnic ancestry and affinity between Persians and Caucasians. Herein we analyzed another Persian population living in the northern province of Tehran and discovered an unexpected increase in the distribution of KIR2DS5 and its linked loci KIR3DS1, -2DS1, and -2DL5 in northern Persians compared with that reported in the southern Persian population. Although the geographic barriers may have limited the gene flow, the impact of the local environment on the natural selection of KIR2DS5 and its linked loci in the northern Persians cannot be completely ruled out. The difference in northern and southern populations in activating KIR gene content creates an appealing hypothesis that KIR2DS5-enriched northern Persians are more resistant to developing clinical conditions demonstrated to be associated with KIR2DS5, such as psoriasis vulgaris, endometriosis, ankylosing spondylitis, and acute rejection of kidney grafts, compared with those living in the southern part of the country.

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2011 Jul;31(7):892-5.

Clinical study on treatment of endometriosis-related infertility patients by laparoscopic surgery in combination of quyu jiedu recipe.

[Article in Chinese]

Qi YH, Lian F.

Source

Clinical College of Shandong University of Traditional Chinese Medicine, Jinan 250011.

Abstract

OBJECTIVE:

To study the clinical efficacy of the laparoscopic surgery in combination of Quyu Jiedu Recipe (QYJDR) on endometriosis (EMs)-related infertility patients.

METHODS:

130 EMs-related infertility patients of blood stasis and toxin accumulation syndrome diagnosed and treated by laparoscopic surgery were randomly assigned to two groups, i.e., the test group (75 cases) and the control group (55 cases). All patients received routine progesterone treatment after laparoscopic surgery. QYJDR was given to patients in the test group after laparoscopic surgery, lasting for twelve months. The pregnancy rate within one year after laparoscopic surgery were compared between the two groups. The Chinese medicine syndrome integrals, serum endometrium antibody (EMAb) and cancer antigen 125 (CA125) levels were compared between before drug therapy and three months after drug therapy.

RESULTS:

The pregnancy rate within one year after laparoscopic surgery was higher in the test group than in the control group [61.33% (46/75) vs 45.45% (25/55)], showing significant difference (P<0.05). The Chinese medicine syndrome integral was (16.07 +/- 6.77) score and (7.25 +/- 3.27) score before and 3 months after drug therapy in the test group, while it was (15.92 +/- 7.51) score and (12.73 +/- 6.12) score in the control group. The Chinese medicine syndrome integral after drug therapy was lower than that before drug therapy in the same group. Besides, the integral difference between before and after drug therapy was higher in the test group than in the control group [(9.12 +/- 6.16) score vs (3.48 +/- 2.06) score)], showing statistical difference (P<0.05). After three-month drug therapy, the serum EMAb negative conversion rate was obviously higher in the test group than in the control group (44.44% vs 15.62%), showing statistical difference (P<0.05). The serum CA125 level was (31.88 +/- 15.78) U/mL before drug therapy and (18.82 +/- 10.08) U/mL three months after drug therapy in the test group, while it was (30.63 +/- 19.28) U/mL and (18.05 +/- 11.20) U/mL respectively in the control group. It was lowered after drug therapy in the two groups with statistical difference (P<0.05). There was no statistical difference between the two groups after drug therapy (P>0.05).

CONCLUSIONS:

The laparoscopic surgery in combination of QYJDR could effectively improve clinical symptoms of EMs patients of blood stasis and toxin accumulation syndrome, promote negative conversion of EMAb, lower serum CA125 levels, and elevate the clinical pregnancy rate. QYJDR is an effective formula in treatment of EMs-related infertility.

J Clin Endocrinol Metab. 2011 Aug 24. [Epub ahead of print]

In Silico Analysis Identifies a Novel Role for Androgens in the Regulation of Human Endometrial Apoptosis.

Marshall E, Lowrey J, Macpherson S, Maybin JA, Collins F, Critchley HO, Saunders PT.

Source

Medical Research Council/University of Edinburgh Centre for Reproductive Health, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.

Abstract

Context: The endometrium is a multicellular, steroid-responsive tissue that undergoes dynamic remodeling every menstrual cycle in preparation for implantation and, in absence of pregnancy, menstruation. Androgen receptors are present in the endometrium. Objective: The objective of the study was to investigate the impact of androgens on human endometrial stromal cells (hESC). Design: Bioinformatics was used to identify an androgen-regulated gene set and processes associated with their function. Regulation of target genes and impact of androgens on cell function were validated using primary hESC. Setting: The study was conducted at the University Research Institute. Patients: Endometrium was collected from women with regular menses; tissues were used for recovery of cells, total mRNA, or protein and for immunohistochemistry. Results: A new endometrial androgen target gene set (n = 15) was identified. Bioinformatics revealed 12 of these genes interacted in one pathway and identified an association with control of cell survival. Dynamic androgen-dependent changes in expression of the gene set were detected in hESC with nine significantly down-regulated at 2 and/or 8 h. Treatment of hESC with dihydrotestosterone reduced staurosporine-induced apoptosis and cell migration/proliferation. Conclusions: Rigorous in silico analysis resulted in identification of a group of androgen-regulated genes expressed in human endometrium. Pathway analysis and functional assays suggest androgen-dependent changes in gene expression may have a significant impact on stromal cell proliferation, migration, and survival. These data provide the platform for further studies on the role of circulatory or local androgens in the regulation of endometrial function and identify androgens as candidates in the pathogenesis of common endometrial disorders including polycystic ovarian syndrome, cancer, and endometriosis.

Tumour Biol. 2011 Aug 24. [Epub ahead of print]

HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases.

Molina R, Escudero JM, Augé JM, Filella X, Foj L, Torné A, Lejarcegui J, Pahisa J.

Source

Laboratory of Clinical Biochemistry (Unit for Cancer Research), Hospital Clínic, Medical School, Barcelona, Spain, rmolina@clinic.ub.es.

Abstract

The aim of this study is to evaluate a new tumour marker, HE4, in comparison with CA 125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in healthy women and in patients with benign and malignant gynaecological diseases. CA 125 and HE4 serum levels were determined in 66 healthy women, 285 patients with benign gynaecological diseases (68 endometriosis, 56 myomas, 137 ovarian cysts and 24 with other diseases), 33 patients with non-active gynaecological cancer and 143 with active gynaecological cancer (111 ovarian cancers). CA 125 and HE4 cut-offs were 35 U/mL and 150 pmol/L, respectively. ROMA algorithm cut-off was 13.1 and 27.7 for premenopausal or postmenopausal women, respectively. HE4, CA 125 and ROMA results were abnormal in 1.5%, 13.6% and 25.8% of healthy women and in 1.1%, 30.2% and 12.3% of patients with benign diseases, respectively. Among patients with cancer, HE4 (in contrast to CA 125) had significantly higher concentrations in ovarian cancer than in other malignancies (p < 0.001). Tumour marker sensitivity in ovarian cancer was 79.3% for HE4, 82.9% for CA 125 and 90.1% for ROMA. Both tumour markers, HE4 and CA 125 were related to tumour stage and histological type, with the lowest concentrations in mucinous tumours. A significantly higher area under the ROC curve was obtained with ROMA and HE4 than with CA 125 in the differential diagnosis of benign gynaecological diseases versus malignant ovarian cancer (0.952, 0.936 and 0.853, respectively). Data from our population indicate that ROMA algorithm might be further improved if it is used only in patients with normal HE4 and abnormal CA 125 serum levels (cancer risk for this profile is 44.4%). ROMA algorithm in HE4 positive had a similar sensitivity and only increases the specificity by 3.2% compared to HE4 alone.

Reproduction. 2011 Aug 23. [Epub ahead of print]

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

Delgado-Rosas F, Gomez R, Ferrero H, Gaytan F, Garcia-Velasco J, Simon C, Pellicer A.

Source

F Delgado-Rosas, fIVI / INCLIVA, Valencia, Spain.

Abstract

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 signalling. The dopamine agonist Cabergoline inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived cabergoline 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 cabergoline in preventing angiogenesis and vascularisation 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/day oral cabergoline, or 50 or 200 µg/kg/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 to the placebo. Given that cabergoline 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.

Int J Surg Pathol. 2011 Aug 23. [Epub ahead of print]

Aggressive Angiomyxoma Admixed With Endometriosis: A Case Report.

Coyne JD.

Source

Royal Liverpool University Hospital, Liverpool, UK.

Abstract

Aggressive angiomyxoma and endometriosis are two apparently unrelated lesions which commonly arise within the pelvis. However, whilst their simultaneous occurrence in this site may be fortuitous, a shared pathogenesis cannot be entirely excluded.

 

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