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What are the experience, and gynaecological and reproductive health outcomes in young adult women who have undergone ovarian tissue cryopreservation (OTC)?A retrospective observational study was conducted at a single institution between May 2019 and February 2021 including 87 women aged over 18 years undergoing OTC. Medical characteristics and questionnaire data collected more than 18 months after OTC were analysed.Close to 74% (n = 64/87) of women had a follow-up consultation and completed the questionnaire. Most women found the information provided on the OTC technique and the strategies proposed to restore fertility with ovarian tissue understandable and useful. The majority of patients thought that OTC had a positive impact on their well-being during disease treatment. Anti-Müllerian hormone serum concentration decreased significantly after treatment (P0.0001) and was significantly lower when patients received chemotherapy before OTC (P = 0.0039). The total cyclophosphamide equivalent dose was significantly higher in women with FSH concentrations above 25 IU/l after treatment (P = 0.0004). More than 70% of women who planned a pregnancy after the end of treatment succeeded, with a natural pregnancy rate close to 53%. Only nine patients (8.0%) underwent ovarian tissue transplantation for fertility restoration and six of them became pregnant and delivered at least once.Young adult women expressed a good satisfaction rate with OTC and that their experience had been beneficial. The usage rate of cryopreserved ovarian tissue remains low. The gynaecological and reproductive health follow-up consultation should be included in the supportive care provided following OTC.

Ubiquitin proteasome system contributes to the regulation of intestinal inflammatory response as its inhibition is associated with tissue damage improvement. We aimed to evaluate whether glutamine is able to limit inflammation by targeting ubiquitin proteasome system in experimental colitis. Colitis was induced in male rats by intrarectal instillation of 2-4-6-trinitrobenzen sulfonic acid (TNBS) at day 1. From day 2 to day 6, rats daily received either an intrarectal instillation of PBS (TNBS/PBS group) or glutamine (TNBS/Gln). Rats were euthanized at day 7 and colonic samples were taken to evaluate ubiqutinated proteins by proteomic approach combining 2D electrophoresis and immunoblots directed against ubiquitin. Results were then confirmed by evaluating total expression of proteins and mRNA levels. Survival rate, TNFα, and IL-1β mRNA were improved in TNBS/Gln compared with TNBS/PBS (p < 0.05). Proteasome activities were affected by TNBS but not by glutamine. We identified eight proteins that were less ubiquitinated in TNBS/PBS compared with controls with no effect of glutamine. Four proteins were more ubiquitinated in TNBS/PBS group and restored in TNBS/Gln group. Finally, 12 ubiquitinated proteins were only affected by glutamine. Among proteins affected by glutamine, eight proteins (GFPT1, Gapdh, Pkm2, LDH, Bcat2, ATP5a1, Vdac1, and Vdac2) were involved in metabolic pathways. In conclusion, glutamine may regulate ubiquitination process during intestinal inflammation.

Anorexia nervosa is a severe eating disorder often leading to malnutrition and cachexia, but its pathophysiology is still poorly defined. Chronic food restriction during anorexia nervosa may induce gut barrier dysfunction, which may contribute to disease development and its complications. Here we have characterized intestinal barrier function in mice with activity-based anorexia (ABA), an animal model of anorexia nervosa.Male C57Bl/6 ABA or limited food access (LFA) mice were placed respectively in cages with or without activity wheel. After 5 days of acclimatization, both ABA and LFA mice had progressively limited access to food from 6 h/d at day 6 to 3 h/d at day 9 and until the end of experiment at day 17. A group of pair-fed mice (PF) was also compared to ABA.On day 17, food intake was lower in ABA than LFA mice (2.0 ± 0.18 g vs. 3.0 ± 0.14 g, p 0.001) and weight loss was more pronounced in ABA and PF compared to LFA mice (23.6 ± 1.6% and 24.7 ± 0.7% vs. 16.5 ± 1.2%; p 0.05). Colonic histology showed decreased thickness of the muscularis layer in ABA compared to LFA mice (p 0.05). Colonic permeability was increased in both ABA and PF compared to LFA mice (p 0.05) but jejunal paracellular permeability was not affected. Expression of claudin-1 in the colon was lower in the ABA than the LFA group (p 0.05), whereas occludin expression remained unaffected.Increased colonic permeability and histological alterations found in ABA mice suggest that intestinal barrier dysfunction may also occur in anorexia nervosa. The role of these alterations in the pathophysiology of anorexia nervosa should be further evaluated.

INTRODUCTIONThe objective is to report a rare tumour of the sinonasal tract and conduct a literature review.Malignant triton tumour is a subtype of malignant schwannoma with rhabdomyoblastic differentiation. It is a very rare tumour, with only 15 reported cases involving the sinonasal region.PRESENTATION OF CASEForty-seven years old female presented with a right-sided epistaxis, progressive right sided nasal obstruction and anosmia and a visible mass in the right nasal cavity. Imaging studies showed a mass extending from the piriform aperture to the nasopharynx in contact with the dura and the orbital content. The mass was biopsied and the result was consistent with malignant triton tumour. The patient refused the surgery at first so chemotherapy with MAID protocol was started. After the fourth course of chemotherapy the treatment was stopped due to patient intolerance and a thrombosis of the jugular vein. Patient then underwent surgery with frontal craniotomy and dural excision, endoscopic control was done at the end to insure a complete removal. The patient received Radiotherapy in the postoperative period (56 Greys). At 5 years of follow up the patient is doing fine with no signs of recurrence and normal ophthalmological findings.DISCUSSIONSixteen cases, including our case, have been reported to date in the literature. The mean age at presentation is 61 years. None of cases were associated with neurofibromatosis type 1. Eight patients were reported to be alive 5 years post-treatment, and 2 patients were reported to have died of the disease. The prognosis for triton tumours in the sinonasal tract is better than that for triton tumours in other locations.CONCLUSIONMalignant triton tumour is a rare malignancy of the sinonasal tract. Otolaryngologists should be aware of this disease. The optimal treatment should include radical resection of the tumour.

Objective The ω-3 polyunsaturated fatty acid therapy in inflammatory bowel disease is focused on the effects on fish oil–derived polyunsaturated fatty acids. We speculated that a vegetal oil rich in α-linolenic acid (ALA) might also inhibit colitis. Therefore, we evaluated whether dietary ALA would decrease the expression of adhesion molecules by inducing the protective enzyme heme oxygenase-1 (HO-1) in a rat colitis model. Methods Colitis was induced at day 0 by an intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas control rats received the vehicle. Rats were fed an ALA-rich formula 450 mg · kg −1 · d −1 , whereas the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from day −7 to day 7). The colonic expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor A receptor-2 (VEGFR2), and HO-1 were studied by immunohistochemistry. Results The ALA-rich diet significantly decreased the expression of ICAM-1, VCAM-1, and VEGFR-2 compared the TNBS group, but it did not affect the expression of HO-1. Conclusion A vegetal ALA-rich formula decreases the expression of ICAM-1, VCAM-1, and VEGFR-2 and independently of HO-1 in rats with TNBS-induced colitis. Further studies are required to evaluate its therapeutic potential in inflammatory bowel disease as an alternative to fish oil.

Proteasome-mediated protein degradation may contribute to the regulation of intestinal inflammation. At the same time, low-grade inflammation and increased intestinal permeability seem to be involved in the pathophysiology of irritable bowel syndrome (IBS). Thus, we aimed to evaluate proteasome composition and activities in colonic mucosa of IBS patients and its putative pathogenic role.Proteasome activities and proteasome subunit expression were measured in colonic mucosa of IBS, Crohn's disease (CD), and control patients by fluorometric assays and western blot, respectively. Expression of inhibitor of kappa B factor (IkappaB alpha) and occludin, a tight junction protein, was also evaluated in colonic biopsies. The degradation of recombinant occludin incubated with protein extracts from colonic mucosa was evaluated in the presence or absence of proteasome inhibitor, MG132.Proteasome trypsin-like activity was increased in IBS patients compared with CD and controls, whereas chymotrypsin-like activity was upregulated in CD patients only. Caspase-like activity was reduced both in IBS and CD patients. IkappaB alpha expression was similar between IBS and controls. In contrast, occludin expression was lower in IBS than in controls, but occludin mRNA level was similar. Protein extracts from IBS patients but not from controls degraded recombinant occludin (20% over 160 min), which was blocked by MG132. Although mast cell number was increased in IBS patients, no correlation was found between this number and proteasome alterations.Our study shows that proteasome alterations are present in the colonic mucosa of IBS patients and may contribute to the pathophysiology of IBS by increasing occludin degradation.

The role of endothelial cells in inflammatory bowel disease has been recently emphasized. Endothelial activation and expression of adhesion molecules are critical for leukocytes recruitment into the inflammatory wall. Compelling evidence demonstrated anti-inflammatory effects of long chain n-3 PUFA in inflammatory models. We previously showed that long chain n-3 PUFA (EPA and DHA) inhibited inflammatory response in epithelial and dendritic cells. As long chain n-3 PUFA treatment led to a decreased expression of adhesion molecules in endothelial cells from other organs, we have now investigated their effect on intestinal endothelial cells in vitro and in colitic rats.In vitro study: Primary culture of human intestinal microvascular endothelial cells (HIMEC) were pre-treated with DHA and then incubated with IL-1β. In vivo study: Colitis was induced in 2 groups at day0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS). Rats received by gavage either fish oil, rich in EPA and DHA (TNBS+n-3) or an isocaloric isolipidic oil formula for 14 days.DHA led to a decreased VCAM-1, TLR4, cyclooxygenase-2 and VEGFR2 expression and a decreased production of IL-6, IL-8 and GM-CSF and a reduced production of PGE(2) and LTB(4) (p 0.001) in IL-1β-induced HIMEC. Similarly, dietary intervention with fish oil rich in EPA and DHA significantly decreased colon production of PGE(2) and LTB(4,) endothelial VCAM-1 and VEGFR2 in rats with colitis.Data obtained from in vitro and in vivo studies reveal a potential anti-angiogenic role of long chain n-3 PUFA in intestinal endothelial cells. This protective effect of long chain n-3 PUFA may partly explain the observed benefit of dietary intake of long chain n-3 PUFA in IBD development.

Introduction et but de l’etude Le systeme ubiquitine-proteasome, systeme de degradation proteique majeur, est implique dans la regulation de nombreux processus cellulaires et dans la reponse inflammatoire intestinale. Des effets protecteurs de la glutamine au niveau intestinal ont ete decrits dans diverses situations physiopathologiques. La glutamine modifie la degradation de l’inhibiteur du facteur de transcription NF-kB par le proteasome en regulant son processus d’ubiquitination. Cependant, les effets de la glutamine sur le processus d’ubiquitination d’autres proteines restent meconnus. Le but de cette etude etait donc de rechercher les proteines dont le taux d’ubiquitination etait modifie par la glutamine au cours d’une colite chez le rat. Materiel et methodes Des rats mâles Sprague Dawley ont ete repartis en 3 groupes (n = 8 / groupe). Une colite a ete induite par une injection rectale d’une solution de TNBS au jour 1. Une injection intra-rectale de glutamine (25 mg kg −1 , 3 ml, TNBS/Gln) ou de PBS (3 ml, TNBS/PBS) a ensuite ete realisee chaque jour de J2 a J6. A J7, les rats ont ete euthanasies et des segments coliques ont ete preleves. L’expression des proteines ubiquitinees a ete etudiee par une approche proteomique combinant une electrophorese bidimensionnelle et un immunoblot dirige contre l’ubiquitine. Apres analyse des variations d’ubiquitination (basee sur un ratio d’expression R > 1,5), les proteines d’interet ont ete identifiees par spectrometrie de masse. Des cytokines pro-inflammatoires (TNFα, IL-1β) ont egalement ete mesurees. Resultats et Analyse statistique Le taux de survie etait signifi-cativement augmente dans le groupe TNBS/Gln par rapport au groupe TNBS/PBS (8/8 vs 5/8, p Conclusion Nos resultats suggerent donc que la glutamine peut moduler le taux d’ubiquitination de proteines au cours d’une reponse inflammatoire intestinale chez le rat, en particulier de proteines impliquees dans la production d’ATP. Des etudes complementaires devront etre menees pour mieux comprendre les mecanismes d’action de la glutamine sur le systeme ubiquitine-pro-teasome et pour savoir si ces effets sont impliques dans les proprietes anti-inflammatoires de la glutamine.