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Circumferential endoscopic resection (ER) of the esophageal mucosa could find its place in the treatment of dysplastic Barrett's esophagus or extensive squamous cell neoplasia. However, the occurrence of esophageal strictures remains a major complication after ER exceeding 75% of the circumference. The aim of this study was to assess the effect of a modified, pH = 2, self-assembling peptide matrix (4[Arg-Ala-Asp-Ala]) (SAP) on the development of esophageal stricture after circumferential ER in a swine model. We performed a circumferential ER in 35 swine under general anesthesia. Five animals were included in the control group, 11 animals received the SAP matrix immediately after the resection, and 11 received the SAP matrix associated to a local steroid immediately after the resection. Follow-up endoscopy and esophagogram were performed before slaughter and necropsy at day 14. Eight treated animals were kept alive until day 28. At day 14, 27% of the animals in the SAP group developed a symptomatic stricture versus 100% in the control group (P  = 0.008) and 50% in the SAP-triamcinolone group (P  = 0.11). Application of an SAP matrix after circumferential ER in the swine allowed a significant reduction of the incidence of symptomatic stricture at day 14. Adding triamcinolone brought no significant improvement. [ABSTRACT FROM AUTHOR]

Background: Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis.Objective and Rationale: We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments.Search Methods: We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment.Outcomes: Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response.Wider Implications: Medical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions. [ABSTRACT FROM AUTHOR]

Study Question: Is endometriosis associated with aberrant sialylation patterns and what is the potential impact of such anomalies on cell migratory properties?Summary Answer: The reduced α-2,6 sialylation patterns in the peritoneal fluid of endometriosis-affected women and in stromal and epithelial cells from endometriotic lesions could be associated with enhanced cell migration.What Is Known Already: Endometriosis is considered to be a benign disease although, like cancer, it has the characteristic of being an invasive disease with cells that have an enhanced capacity to migrate. Aberrant sialylation has been reported in various malignancies and it has been linked to tumour invasion and metastasis.Study Design, Size, Duration: We conducted a prospective laboratory study in a tertiary-care university hospital. We investigated non-pregnant patients who were <42 years of age (n = 273) when they underwent surgery for a benign gynaecological condition.Participants/materials, Setting, Methods: The study population consisted of 102 women with histologically proven endometriosis and 71 endometriosis-free controls, who underwent a complete surgical exploration of the abdominopelvic cavity. Peritoneal fluids were collected during the surgical procedures, and endometrial and endometriotic biopsies were performed on all of the patients to generate stromal and epithelial primary cell cultures. The expression of α-2,6-sialyltransferase (ST6GALNAC1) was studied in eutopic and ectopic endometria of endometriosis patients and in eutopic endometria of controls by reverse transcription followed by quantitative real-time polymerase chain reaction (RT-qPCR). The α-2,6 sialylation levels were measured by ELISA in the peritoneal fluids of patients and controls and by western-blot in primary endometrial and endometriotic cell cultures using Sambucus nigra agglutinin (SNA), an α-2,6 sialic acid-binding lectin. A transwell migration assay after incubation of the cells with neuraminidase was also performed to evaluate the impact of desialylation on eutopic endometrial stromal cell migration.Main Results and the Role Of Chance: ST6GALNAC1 gene expression was significantly lower in endometriotic lesions compared to that in eutopic endometrium of endometriosis-affected patients and healthy endometrium (16-fold for both; P < 0.01). We observed a significant reduction in SNA levels in the peritoneal fluids of endometriosis-affected women compared to control women (median optic density (OD), 0.257; range, 0.215-0.279 versus median OD, 0.278; range 0.238-0.285; P < 0.01), as well as in stromal (mean OD, 705 907; standard error of the mean (SEM), 141 549 versus mean OD, 1.16 × 106; SEM, 107,271; P < 0.05) and epithelial (mean OD, 485 706; SEM, 179 681 versus mean OD, 1.25 × 106; SEM, 232 120; P < 0.05) ectopic endometriotic cells compared to control eutopic cells, indicating reduced α-2,6 sialylation. Finally, in the transwell migration assay, the eutopic endometrial cells of endometriosis patients migrated significantly more into the lower chamber after incubation with neuraminidase, indicating enhanced migration by these cells after desialylation.Large Scale Data: N/A.Limitations, Reasons For Caution: Our control group involved patients operated for benign gynaecological conditions (e.g. tubal infertility, uterine fibroids or ovarian cysts) which may also be associated with altered sialylation patterns.Wider Implications Of the Findings: The hyposialylation pattern of endometriotic cells appeared to be associated with enhanced migratory abilities, which might contribute to the establishment of early endometriotic implants. Further research is needed to confirm these findings, as this could lead to new potential therapeutic targets for this complex disorder.Study Funding and Competing Interest(s): No external funding was received and there are no conflicts of interest. [ABSTRACT FROM AUTHOR]

We report on 11 cases of specific polysaccharide antibody deficiency (SPAD) revealed in adulthood by severe infections with encapsulated bacteria. Given that immunoglobulin replacement therapy can effectively prevent the recurrence of bacterial infections in this context, SPAD should be considered once other antibody deficiencies have been ruled out. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Are protein oxidative stress markers [thiols, advanced oxidation protein products (AOPP), protein carbonyls and nitrates/nitrites] in perioperative peritoneal fluid higher in women with histologically proven endometriosis when compared with endometriosis-free controls? SUMMARY ANSWER: Protein oxidative stress markers are significantly increased in peritoneal fluids from women with deep infiltratingendometriosis with intestinal involvement when compared with endometriosis-free controls. WHAT IS KNOWN ALREADY: Endometriosis is a common gynaecologic condition characterized by an important inflammatory process. Various source of evidence support the role of oxidative stress in the development of endometriosis. STUDY DESIGN, SIZE, DURATION: We conducted a prospective laboratory study in a tertiary-care university hospital between January 2011 and December 2012, and included 235 non-pregnant women, younger than 42 year old, undergoing surgery for a benign gynaecological condition. PARTICIPANTS/MATERIALS, SETTING, METHODS: After complete surgical exploration of the abdomino-pelvic cavity, 150 women with histologically proven endometriosis and 85 endometriosis-free controls women were enrolled. Women with endometriosis were staged according to a surgical classification in three different phenotypes of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deeply infiltrating endometriosis (DIE). Perioperative peritoneal fluids samples were obtained from all study participants. Thiols, AOPP, proteincarbonyls and nitrates/nitrites were assayed in all peritoneal samples. MAIN RESULTS AND THE ROLE OF CHANCE: Concentrations of peritoneal AOPP were significantly higher in endometriosis patients than in the control group (median, 128.9 µmol/l; range, 0.3-1180.1 versus median, 77.8 µmol/l; range, 0.8-616.1; P < 0.001). In a similar manner concentrations of peritoneal nitrates/nitrites were higher in endometriosis patients than in the control group (median, 24.8 µmol/l; range, 1.6-681.6 versus median, 18.5 µmol/l; range, 1.6-184.5; P < 0.05). According to the surgical classification, peritoneal fluids protein AOPP and nitrates/nitrites were significantly increased only in DIE samples when compared with controls (P < 0.001 and P < 0.05; respectively), whereas the others forms of endometriosis(SUP and OMA) showed non-statistically significant increases. We found positive correlations between peritoneal fluids AOPP concentrations, nitrites/nitrates levels and the total number of intestinal DIE lesions (r = 0.464; P < 0.001 and r = 0.366; P = 0.007; respectively). LIMITATIONS, REASONS FOR CAUTION: Inclusion of only surgical patients may constitute a possible selection bias. In fact, our control group involved women who underwent surgery for benign gynaecological conditions. This specificity of our control group may lead to biases stemming from the fact that some of these conditions, such as fibroids, ovarian cysts or tubal infertility, might be associated with altered peritoneal protein soxidative stress markers. WIDER IMPLICATIONS OF THE FINDINGS: We demonstrate the existence of a significantly increased protein oxidative stress status in peritoneal fluid from women with endometriosis especially in cases of DIE with intestinal involvement. This study opens the way to future more mechanistics studies to determine the exact role of protein oxidative stress in the pathogenesis of endometriosis. Even if an association does not establish proof of cause and effect, these intrinsic biochemical characteristics of endometriosis may lead to the evaluation of therapeutic approaches targeting oxidative imbalance. STUDY FUNDING/COMPETING INTERESTS: No funding was used for this study. The authors have no conflict of interest. [ABSTRACT FROM AUTHOR]

This review and meta-analysis confirmed that the duration of seroprotection conferred by most licensed vaccines was shorter in patients infected with human immunodeficiency virus. Implications for the monitoring of antibody levels and timing of revaccination in these patients are therefore discussed.Vaccine-induced antibodies may wane more quickly in persons living with human immunodeficiency virus (HIV) than in healthy individuals. We reviewed the literature on vaccines routinely recommended in HIV-infected patients to estimate how seroprotection decreases over time in those who initially responded to immunization. For each study retrieved from the literature, the decrease of seroprotection was modeled with a log binomial generalized linear model, and data were pooled in a meta-analysis to provide estimates of seroprotection 2 and 5 years after the last vaccine administration. Our analyses confirmed that the duration of seroprotection was shorter in HIV-infected patients and that with current guidelines, a substantial proportion of patients would have lost protective antibodies before a booster was proposed. We therefore discuss the implications for the monitoring of antibody levels and timing of revaccination in these patients. [ABSTRACT FROM PUBLISHER]

BACKGROUND Interleukin 33 (IL-33) is a cytokine involved in fibrotic disorders. We have analyzed IL-33 levels in the sera and peritoneal fluids of women with various forms of endometriosis and investigated the correlation with disease activity. METHODS We conducted a prospective laboratory study in a tertiary-care university hospital between January 2005 and December 2010. Five hundred and ten women with histologically proven endometriosis and 132 endometriosis-free controls were enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Blood samples and peritoneal fluids were obtained before and during surgical procedures, respectively. IL-33 was measured by an enzyme-linked immunosorbent assay in sera and peritoneal fluids, and the concentrations correlated with the extent and the severity of endometriotic lesions. RESULTS IL-33 was detectable in 23.1% of serum samples from all 642 women studied and 75.0% of peritoneal fluid samples studied (44 women with endometriosis and 36 controls). Serum IL-33 was higher in deeply infiltrating endometriosis (DIE) (median, 104.9 pg/ml; range, 8.0–104.9) than in endometriosis-free women (median, 61.3 pg/ml; range, 7.5–526.0; P = 0.022) or in women affected by superficial endometriosis (median, 36.8 pg/ml; range, 7.5–179.0; P < 0.001). Peritoneal IL-33 was higher in DIE than in endometriosis-free women (median, 642.0 pg/ml; range, 25.9–3350.6 versus median, 194.2 pg/ml; range, 12.7–1818.2, respectively; P = 0.003). We found positive correlations between serum IL-33 concentration and intensity of dysmenorrhea (r = 0.174; P = 0.028) and gastrointestinal symptoms (r = 0.199; P = 0.027), total number of DIE lesions (r = 0.224; P = 0.016) and the worst DIE lesion (r = 0.299; P < 0.001). CONCLUSIONS In spite of the number of samples with undetectable levels, serum IL-33 is abnormally elevated in women with endometriosis and principally in DIE. Elevated serum IL-33 is correlated with the intensity of preoperative painful symptoms, and with the extent and severity of the DIE. IL-33 may be considered as a novel cytokine involved in the pathogenesis of DIE. [ABSTRACT FROM AUTHOR]

Background: Anticancer drugs act by increasing intracellular hydrogen peroxide levels. Mangafodipir, a superoxide dismutase (SOD) mimic with catalase and glutathione reductase activities, protects normal cells from apoptosis induced by H2O2. We investigated its and other oxidative stress modulators' effects on anticancer drug activity in vitro and in vivo. Methods: Cell lysis and intracellular reactive oxygen species levels were assessed in vitro in human leukocytes from healthy subjects and in marine CT26 colon cancer cells. Cells were exposed to the chemotherapeutic agents paclitaxel, oxaliplatin, or 5-fluorouracil, either in the presence or absence of mangafodipir and other oxidative stress modulators. Cell viability was evaluated by the methylthiazoletetrazolium assay. The effects of mangafodipir and other oxidative stress modulators on peripheral blood counts and on tumor growth were studied in BALB/c mice that were implanted with CT26 tumors and treated with 20 mg/kg paclitaxel. Survival of BALB/c mice infected with Staphylococcus aureus was also examined by treatment group. Statistical tests were two-sided. Results: In vitro lysis of leukocytes exposed to paclitaxel, oxaliplatin, or 5-fluorouracil in combination with mangafodipir was decreased by 46% (95% confidence interval [CI] = 44% to 48%), 30.5% (95% CI = 29% to 32%), and 15% (95% C1 = 10% to 20%), compared with lysis of cells treated with anticancer agent alone. Mangafodipir also statistically significantly enhanced in vitro anticancer drug cytotoxicity toward CT26 cancer cells. In vivo, mangafodipir protected mice against paclitaxel-induced leukopenia. Moreover, the survival rate of mice infected with S. aureus and treated with paclitaxel was higher when mangafodipir was also administered (survival: 3 of 17 versus 14 of 17, P<.001). In addition, mangafodipir amplified the inhibitory effect of paclitaxel on CT26 tumor growth in mice. Conclusions: Mangafodipir decreased hematotoxicity and enhanced cytotoxicity of anticancer agents. [ABSTRACT FROM AUTHOR]