We read with interest the publication by Wang and colleagues on the off-label use of Mepolizumab for the treatment of eosinophilic cystitis in a 77-year-old patient [1].The authors presented another patient with idiopathic eosinophilic cystitis successfully treated with mepolizumab [1].

We formerly demonstrated that GPR40 prevents from osteoporosis establishment using synthetic agonist. Here, we questioned whether stimulation of GPR40 by fatty acids, the natural ligands for GPR40, may parallel with its described beneficial effects on bone. In this study we demonstrated for the first time that GPR40 limits bone loss induced by ovariectomy upon high fat diet. Taken together, our results demonstrate that GPR40 mediates beneficial effects of high fat diets mainly by targeting the bone cell coupling and subsequent osteoclastic bone resorption.

Background and Purpose A high recurrence rate after medical treatment is a major clinical problem for patients with endometriosis. Here, we have evaluated the in vitro effects of combined treatment with MK2206 (an AKT inhibitor) + chloroquine on cell growth and regrowth of endometriotic stromal cells and the in vivo effects on endometriotic implants in a mouse xenograft model of endometriosis. Experimental Approach We evaluated the effects of autophagy inhibition by knockdown of the ATG13, Beclin‐1 and ATG12 genes and pharmacological agents (chloroquine, bafilomycin A1 or 3‐methyalanine) individually and in combination with MK2206 on cell growth and/or cell regrowth of endometriotic stromal cells in vitro . Furthermore, we evaluated treatment with MK2206 + chloroquine on endometriotic implants in a mouse xenograft model of endometriosis. Key Results Combined treatment with MK2206 and chloroquine markedly reduced cell growth and regrowth after discontinuation of treatment in endometriotic stromal cells compared with cells treated with either drug alone. Autophagy inhibition by ATG13, Beclin‐1 or ATG12 gene knockdown only affected regrowth of endometriotic stromal cells, but not endometrial stromal cells from the same patients, after a 72 h discontinuation of the combined treatment. Furthermore, combined treatment reduced the size of endometriotic implants, whereas no effects on endometriotic implants treated with either drug alone were observed in a mouse xenograft model of endometriosis. Conclusions and Implications The present findings suggest that a novel strategy for treatment of endometriosis may involve decreasing the number of endometriotic cells that can survive treatment and then preventing regrowth by autophagy inhibition.

European Annals of Otorhinolaryngology, Head and Neck Diseases - Vol. 129 - N° 4 - p. 211-213

La trachéopathie ossifiante ou trachéobronchopathie ostéochondroplastique (TBOP) est une maladie rare d’étiologie inconnue, qui occasionne des manifestations pouvant simuler un asthme. Nous rapportons une observation colligée au mois d’octobre 2012. Il s’agit d’une patiente âgée de 47 ans suivie pour asthme sévère non contrôlé, hospitalisée suite à des épisodes d’hémoptysies minimes. L’examen clinique avait noté un wheezing et des râles sibilants diffus à l’auscultation. Le diagnostic de trachéopathie ossifiante a été soulevé devant les données de l’imagerie radiologique et l’aspect endoscopique caractéristique. Le traitement n’est que symptomatique.Tracheopathia osteoplastica or tracheobronchopathia osteochondroplastica (TPO) is a rare disease of unknown etiology which causes symptoms that may mimic asthma. We report a case observed in October 2012. The 47-year-old patient, who was being followed for severe uncontrolled asthma, was hospitalized after episodes of minimal hemoptysis. Clinical examination revealed wheezing and sibilant rales on auscultation. A diagnosis of tracheopathia osteoplastica was made before the radiologic imaging data and endoscopic features were obtained. The only treatment is symptomatic.

The objective of the present study was to evaluate the effects of small molecule antagonists of Tcf/beta-catenin complex on proliferation, migration and invasion of endometrial and endometriotic cells. In Vitro study. Samples of endometriosis and the matched eutopic endometrium were collected during laparoscopic surgery. Cell proliferation, migration and invasion, expression of Tcf/beta-catenin target genes and the MMP-2 and MMP-9 activity of endometrial and endometriotic cells were analyzed after the treatment with small molecule antagonists of Tcf/beta-catenin complex. Statistical significance was defined as P<0.05. Treatment with 6.25 μM PKF115-584 for 48h inhibited proliferation of endometriotic epithelial cells (deep infiltrating endometriosis (DIE): 47.9±7.2%, n=16; ovarian endometriosis (OV): 25.3±7.6%, n=13; peritoneal endometriosis (PE): 43.1±10.3%, n=12, mean±SEM) and endometriotic stromal cells (DIE: 30.4±8.9%, n=18; OV: 11.1±9.4%, n=15; PE: 24.1±11.8%, n=14). However, the inhibitory effects were significantly higher in the matched endometrium than those of endometriosis. Inhibition of migration and invasion of epithelial cells were significantly greater in endometriosis (n=16) compared to those of the matched eutopic endometrium (n=16) (migration: 61.1±4.1%, 38.3±6.0%, respectively; invasion: 63.8±5.1%, 38.5±7.5%, respectively). There was no significant difference in inhibition of migration of stromal cells between endometriosis (n=16) and the matched eutopic endometrium (n=16) (71.1±1.6%, 62.9±7.3%, respectively), whereas inhibition of invasion of stromal cells was significantly greater in endometriosis compared with the matched eutopic endometrium (67.0±3.1%, 37.6±4.1%, respectively). Small molecule antagonists of Tcf/beta-catenin complex might be effective in inhibition of migration and invasion of endometriotic cells.

Introduction: Tumor microenvironment of colorectal carcinoma (CRC) is a complex association of non neoplastic and cancer cells and a large amount of microorganisms that could be linked to cancer by various mechanisms including chronic inflammation and production of carcinogenic metabolites.E. coli is a consistent commensal of the human gut microbiota but some pathogenic strains have acquired the ability to produce toxins that can interfere with eukaryotic cell cycle or directly induce DNA damages.In this study, we analyzed the E. coli population associated with the colonic mucosa of human colorectal cancers and investigated the ability of CRC-associated E. coli to induce colonic tumorigenesis in multiple intestinal neoplasia (Min) mice with mutation in the APC gene, which is altered in the majority of CRC.Material and Methods: Tumors and normal mucosa from CRC patients (n = 52) and healthy mucosa for diverticulosis controls (n = 30) were collected.Mucosa-associated and internalized E. coli were quantified and characterized.Min mice were inoculated with a CRC-associated E. coli strain (strain CRC20), non pathogenic E. coli (strain K-12 MG1655) or PBS alone.Fecal bacterial colonization was quantified.Colonic samples were analyzed (macroscopy, histology).Results: Significantly higher numbers of mucosa-adherent and mucosainternalized E. coli were observed in tumors compared to normal tissue from control and CRC patients (at distance of the tumor).A statistically significant relationship was found between the presence of mucosa-associated E. coli and poor prognostic factors for CRC as tumor staging, lymph node status.In vitro, CRC-associated E. coli strains were able to invade and to persist in intestinal epithelial cells.Electron microscopy analysis of infected cultured cells indicated that bacteria induce the elongation of eukaryotic cell membranes and are internalized within endocytic vacuoles.Infections of Min mice with CRC20 E. coli indicated that this strain was able to persist at a high level in the gut up to 10 weeks after infection in comparison to non pathogenic E. coli that was no longer detected 2 weeks after infection.CRC20-colonized mice showed a marked increased number of visible colonic polyps at 10 weeks compared to controls.Histological analyzes confirmed that all these polyps were adenocarcinoma.Conclusion: These data support that mucosa-adherent pathogenic E. coli may be a cofactor in the pathogenesis of colorectal cancer.

Introduction: Le but de cette étude était d'évaluer la sensibilité, la spécificité et la rentabilité diagnostique de la biopsie guidée par échoendoscopie (BG/EE) pour les syndromes lymphoprolifératifs à partir d'une série rétrospective réalisée dans un centre expert.

There is growing evidence to suggest that endometriosis may arise from stem cells. Recently, Masuda et al. demonstrated that the ATP-binding cassette transporter G2 (ABCG2) + population, which presumably includes endometrial side population (ESP) cells having endometrial stem cell-like properties is localized exclusively in the endothelium of the human cycling endometrium (PLoS One. 2010;5:e10387). The objective of the present study was to investigate ABCG2 expression in endometriosis. Prospective study Samples of deep infiltrating endometriosis (n = 68), ovarian endometriosis (n = 55) and superficial peritoneal endometriosis (red lesions: n = 30, black lesions: n = 46) were collected during laparoscopic surgery. In addition, samples of menstrual endometrium, scar endometriosis following cesarean section, cutaneous umbilical endometriosis, and bowel endometriosis with pre-operative hormonal treatment, were included in the present study for comparison. Immunohistochemical staining was performed on paraffin sections using monoclonal antibody against ABCG2. Double immunofluorescence staining using CD31 and ABCG2 antibodies was performed to examine the localization of CD31+ ABCG2+ cells. The percentage of ABCG2 positive samples was significantly higher in deep infiltrating endometriosis (72.0 %, 49/68, P<.05) compared to that of ovarian endometriosis (21.8%, 12/55), red peritoneal lesions (46.7%, 14/30) and black peritoneal lesions (10.9%, 5/46). In addition, ABCG2 expression was detected in 10 samples of scar endometriosis following cesarean section (83.3%, 10/12), 3 samples of cutaneous umbilical endometriosis (60%, 3/5) and 22 samples of bowel endometriosis with pre-operative hormonal treatment (100%, 22/22). The present findings suggest that some endometriosis may arise from stem cells. In addition, ABCG2 might be of interest for a therapeutic target in deep infiltrating endometriosis.

OBJECTIVE: Our previous study demonstrated that expression levels of E-cadherin were distinctive among different forms of endometriosis. We further investigated several markers of epithelial-mesenchymal transition (EMT) (N-cadherin, vimentin, S100A4, dephosphorylated form of beta-catenin) in endometriosis.DESIGN: Prospective study.MATERIALS AND METHODS: Samples of deep infiltrating endometriosis (n= 61), ovarian endometriosis (n=48) and superficial peritoneal endometriosis (red lesions: n=30, black lesions: n = 46) were collected during laparoscopic surgery. In addition, samples of menstrual endometrium, abdominal wall endometriosis, other benign ovarian cysts, carcinoma arising in ovarian endometriosis, colon endometriosis and scar endometriosis, were included in the present study for comparison. Immunohistochemical staining was performed on paraffin sections and quantitation of immunostained cells (percentage of immunostained surface × mean staining intensity) was obtained using a computerized image analysis system.RESULTS: Vimentin expression was detected in the menstrual endometrium, whereas no expression of N-cadherin, S100A4 and dephosphorylated beta-catenin was detected. S100A4 expression was significantly lower in deep infiltrating endometriosis compared to that of ovarian endometriosis and red peritoneal lesions. Vimentin expression was significantly lower in ovarian endometriosis compared to that of deep infiltrating endometriosis, red and black peritoneal lesions. In addition, vimentin expression in deep infiltrating endometriosis, red and black peritoneal lesions was significantly higher than that of menstrual endometrium. Dephosphorylated beta-catenin expression was significantly higher in deep infiltrating endometriosis compared to that of ovarian endometriosis, red and black peritoneal lesions.CONCLUSION: The present findings suggested that markers of EMT might be gained depending on the microenvironment during the evolution of endometriotic implants. OBJECTIVE: Our previous study demonstrated that expression levels of E-cadherin were distinctive among different forms of endometriosis. We further investigated several markers of epithelial-mesenchymal transition (EMT) (N-cadherin, vimentin, S100A4, dephosphorylated form of beta-catenin) in endometriosis. DESIGN: Prospective study. MATERIALS AND METHODS: Samples of deep infiltrating endometriosis (n= 61), ovarian endometriosis (n=48) and superficial peritoneal endometriosis (red lesions: n=30, black lesions: n = 46) were collected during laparoscopic surgery. In addition, samples of menstrual endometrium, abdominal wall endometriosis, other benign ovarian cysts, carcinoma arising in ovarian endometriosis, colon endometriosis and scar endometriosis, were included in the present study for comparison. Immunohistochemical staining was performed on paraffin sections and quantitation of immunostained cells (percentage of immunostained surface × mean staining intensity) was obtained using a computerized image analysis system. RESULTS: Vimentin expression was detected in the menstrual endometrium, whereas no expression of N-cadherin, S100A4 and dephosphorylated beta-catenin was detected. S100A4 expression was significantly lower in deep infiltrating endometriosis compared to that of ovarian endometriosis and red peritoneal lesions. Vimentin expression was significantly lower in ovarian endometriosis compared to that of deep infiltrating endometriosis, red and black peritoneal lesions. In addition, vimentin expression in deep infiltrating endometriosis, red and black peritoneal lesions was significantly higher than that of menstrual endometrium. Dephosphorylated beta-catenin expression was significantly higher in deep infiltrating endometriosis compared to that of ovarian endometriosis, red and black peritoneal lesions. CONCLUSION: The present findings suggested that markers of EMT might be gained depending on the microenvironment during the evolution of endometriotic implants.

BACKGROUNDTo better understand the infertility of patients with Robertsonian translocation, the biochemical and ultrastructural apoptotic characteristics of apoptosis in the sperm of patients and fertile donors were studied.METHODSEjaculated sperm samples of seven Robertsonian translocation carriers and seven fertile donors were analyzed after cryopreservation. The proportion of both viable and dead spermatozoa expressing activated caspases was detected by flow cytometry through the use of different specific carboxyfluorescein-labeled caspase inhibitors. Sperm DNA fragmentation was evaluated by the TUNEL method. The percentages of intact spermatozoa or spermatozoa with ultrastructural features of apoptosis, immaturity or necrosis were estimated by electron microscopy. Meiotic segregation analysis was performed by FISH.RESULTSSignificantly lower concentration, forward motility and normal morphology of spermatozoa were found in ejaculated samples of the Robertsonian patients than fertile donors. Compared with the control group, in Robertsonian translocation carriers: (i) the caspase assays showed a significantly increased (P < 0.05) proportion of viable spermatozoa with activated poly-caspases (57.4 versus 25.8%), caspase-3 (43.5 versus 13.4%), caspase-8 (44.4 versus 17.1%) and caspase-9 (42.4 versus 10.0%); (ii) the rate of DNA fragmentation was higher (26.3 versus 12.8%); and (iii) sperm ultrastructural examination highlighted a higher percentage of immature (28.0 versus 10.0%) and apoptotic (24.5 versus 18.5%) spermatozoa. FISH study showed predominant normal/balanced spermatozoa (78.34-85.53%).CONCLUSIONSThese results show a predominant proportion of balanced and normal gametes and higher numbers of spermatozoa showing apoptosis and immaturity features in oligoasthenozoospermic Robertsonian translocation carriers than in fertile donors. This suggests defects in spermatogenesis and especially spermiogenesis of these infertile patients.

vation was only inhibited by EN, which vice versa increased pro-inflammatory cytokine secretion.In mucosal T cells, both PN and EN reduced LPMC activation (an affect probably wanted in IBD) and reduced pro-inflammatory cytokine secretion.Our study provides evidence, that EN and PN are both capable to modulate intestinal barrier and T cell function and thus are capable to protect the host.