Potential use of ellagic acid for endometriosis treatment: its effect on a human endometrial cell cycle, adhesion and migration.

Endometriosis is a common and challenging condition of reproductive-aged women that is defined as the presence of endometrial-like tissue outside the uterine cavity. Despite its prevalence, there is still no effective therapeutics; so we aim to evaluate the ellagic acid (EA) effect on the most relevant aspects that are known to be altered in endometriosis. Endometrial primary cultures from women with and without endometriosis and endometrial cell lines were incubated with EA (50 and 100 µM) for 24 and 48 h. The results demonstrated that EA arrests an endometrial stromal cell cycle on the G2/M phase, after 48 h. In addition, 100 µM EA treatment significantly decreased ECC-1 cell migration at 20 h and T-HESC cell migration at 10 h and 20 h, while 50 µM EA significantly decreased T-HESC cell migration at 20 h. On the other hand, we proved that the treatment with EA for 24 h reduces T-HESC and ECC-1 adhesion to plastic. However, we did not find an effect of EA on cell proliferation. EA has an inhibitory effect on endometrial cell adhesion, migration and cell cycle progression in vitro. These highlight the idea to investigate natural compounds as novel and promising candidates for therapeutic treatment of endometriosis.

Natural therapies assessment for the treatment of endometriosis.

STUDY QUESTION: Can resveratrol and epigallocatechin-3-gallate (EGCG) inhibit the growth and survival of endometriotic-like lesions in vivo in a BALB/c model of endometriosis, and in vitro in primary cultures of human endometrial epithelial cells (EECs)? SUMMARY ANSWER: Resveratrol and EGCG exerted a potent inhibitory effect on the development of endometriosis in a BALB/c murine model and on the survival of EECs. WHAT IS KNOWN ALREADY: Endometriosis is a common condition associated with infertility and pelvic pain in women of reproductive age. Resveratrol and EGCG are two polyphenols with anticarcinogenic and antioxidant properties that have been proposed as natural therapies to treat endometriosis. STUDY DESIGN, SIZE, DURATION: Fifty-six 2-month-old female BALB/c mice underwent surgical induction of endometriosis. Treatments with resveratrol or EGCG started 15 days post-surgery and continued for 4 weeks. Human biopsies were taken with a metal Novak curette from the posterior uterine wall from 16 patients with untreated endometriosis and 15 controls who underwent diagnostic laparoscopy for infertility. MATERIALS, SETTING, METHODS: After the treatments, animals were sacrificed and lesions were counted, measured, excised and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for cell proliferation and vascularization assessment in the lesions. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique was performed for apoptosis evaluation. Peritoneal fluid was collected to analyze vascular endothelial growth factor levels. Human EECs were purified from proliferative-phase endometrial biopsies and cultured. The effect of both polyphenols on cell proliferation was determined by a colorimetric assay using the CellTiter 96®AQueous One Solution Cell Proliferation Assay kit and on apoptosis by the TUNEL technique, using an In Situ Cell Death Detection Kit with Fluorescein. MAIN RESULTS: In the mouse model, both treatments significantly reduced the mean number (P < 0.05 versus control) and the volume of established lesions (P < 0.05 versus control). Treatments consistently statistically significantly diminished cell proliferation (resveratrol P < 0.01 and EGCG P < 0.05, versus control), reduced vascular density (resveratrol P < 0.01 and EGCG P < 0.001, versus control) and increased apoptosis within the lesions (resveratrol P < 0.01 and EGCG P < 0.05, versus control). Both compounds induced reduction in human EEC proliferation (P < 0.05 versus basal) and increased apoptosis (P < 0.05 versus basal) in primary cultures. LIMITATIONS: In vitro studies were only carried out in epithelial cells from human eutopic endometrium. WIDER IMPLICATIONS OF THE FINDINGS: The present findings are promising and will assist the development of novel natural treatments for endometriosis. STUDY FUNDING: This study was supported by ANPCYT (PICT 6384 BID 1201 OC-AR) and CONICET (PIP 5471), Argentina. None of the authors has any conflict of interest to declare.

Deep vein thrombosis after total hip and knee arthroplasty in Indian patients.

BACKGROUND: Deep vein thrombosis (DVT) is one of the most common complications of total hip (THA) and total knee arthroplasty (TKA). Though the reported incidence of DVT is very high, that of proximal DVT is low and that of fatal thromboembolism is very low. Hence the issue of prophylaxis for DVT remains controversial. The incidence of DVT is based on various studies in European and American populations. The Asian population is genetically and socially quite different from American and European populations, and the incidence of DVT can be quite different. Therefore a prospective study was initiated at our centre to determine incidence of DVT after THA and TKA in Indian patients. METHODS: A prospective study was conducted on 60 hips in 45 patients and 46 knees in 26 patients who underwent THA and TKA respectively, without any known risk factors for thromboembolic disease. DVT was studied by preoperative and postoperative serial colour Doppler ultrasonography. No prophylaxis was given to any of the patients. RESULTS: DVT was found in two patients who had undergone THA. No case of DVT was detected in any patient who had undergone TKA. CONCLUSION: These results suggest that the incidence of DVT in Indian patients is very low and is not comparable with American and European populations. It is therefore not cost effective to advise prophylaxis in Indian patients undergoing THA/TKA who have no known risk factors for DVT.

Is preoperative selection of patients with cystic adnexal masses essential for laparoscopic treatment?

STUDY OBJECTIVE: To analyze indications for preoperative selection of patients with cystic adnexal masses to be treated by laparoscopic surgery. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University and military hospitals. PATIENTS: Three hundred sixteen women with adnexal masses. INTERVENTION: Before laparoscopy, 214 patients underwent evaluation (size of adnexal mass, ultrasonographic image, CA 125, suspicious clinical diagnosis); in 102 women laparoscopies were performed without taking these factors into account. MEASUREMENTS AND MAIN RESULTS: In the first center 99% of women were treated by laparoscopic surgery. One (0.4%) tumor of low malignant potential detected by deferred biopsy was operated on. In the second center 98% of cases were performed laparoscopically. In 3.9% of women carcinomas were detected intraoperatively and were treated by laparotomy (p = 0.04). CONCLUSION: Laparoscopy is appropriate management of cystic adnexal masses, with a very low risk of unintentionally operating an ovarian carcinoma if a thorough preoperative evaluation is conducted. Only in centers where surgeons have enough training to cope with ovarian cancer may this evaluation be deferred, since conversion to laparotomy should be considered a second therapeutic step, and not an incorrect indication for laparoscopy. In centers where surgeons have no such training, strict preoperative selection of patients is mandatory

Effect of peritoneal fluid from patients with mild and severe endometriosis on endometrial stromal cell proliferation.

The aim of this study was to evaluate and compare the mitogenic effect of peritoneal fluid (PF) from women with mild and severe endometriosis on the endometrial stromal cell proliferation. Increasing concentrations of PF from women with and without mild or severe endometriosis were added to primary endometrial stromal cell cultures and 3H-thymidine incorporation was used to assess DNA synthesis in these cultures. PF from women with mild endometriosis induced a statistically significant dose-dependent increase in stromal cell thymidine uptake ranged from 5.8 to 14.5 fold, whereas PF from women with severe endometriosis produced an average 51% inhibition of stromal cell proliferation of compared with cells exposed to non-endometriosis PF or exposed to nutrient medium supplemented with 2.5% calf serum alone. PF samples from patients with stage I endometriosis induced a statistically dose-dependent increase in stromal cell proliferation, whereas PF from patients with stage IV endometriosis caused a significant inhibition.