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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.

Pre-pubertal murine models of acute colitis are lacking. Magnetic resonance colonography (MRC) is a promising minimally invasive tool to assess colitis. We aimed to: 1/ Adapt a model of acute experimental colitis to pre-pubertal rats and determine whether MRC characteristics correlate with histological inflammation. 2/ Test this model by administering a diet supplemented in transforming growth factor β2 to reverse inflammation. Twenty-four rats were randomized at weaning to one of 3 groups: Trinitrobenzene Sulfonic Acid (TNBS) group (n = 8) fed a standard diet, that received an intra-rectal 60 mg/kg dose of TNBS-ethanol; Control group (n = 8) fed standard diet, that received a dose of intra-rectal PBS; TNBS+MODULEN group (n = 8) that received a dose of TNBS and were exclusively fed MODULEN-IBD® after induction of colitis. One week after induction of colitis, rats were assessed by MRC, colon histopathology and inflammation markers (Interleukin 1β, Tumor necrosis factor α, Nitric Oxide Synthase 2 and Cyclooxygenase 2). TNBS induced typical features of acute colitis on histopathology and MRC (increased colon wall thickness, increased colon intensity on T2-weighted images, target sign, ulcers). Treatment with MODULEN-IBD® did not reduce signs of colitis on MRC. Inflammatory marker expression did not differ among study groups.

Intestinal fibrosis is a frequent complication in inflammatory bowel diseases (IBD). It is a challenge to identify environmental factors such as diet that may be driving this risk. Intestinal fibrosis result from accumulation of extracellular matrix (ECM) proteins secreted by myofibroblasts. Factors promoting intestinal fibrosis are unknown, but diet appears to be a critical component in its development. Consumption of salt above nutritional recommendations can exacerbate chronic inflammation. So far, high salt diet (HSD) have not been thoroughly investigated in the context of intestinal fibrosis associated to IBD. In the present study, we analyze the role of dietary salt in TNBS chronic colitis induced in rat, an intestinal fibrosis model, or in human colon fibroblast cells. Here, we have shown that high-salt diet exacerbates undernutrition and promoted ECM-associated proteins in fibroblasts. Taken together, our results suggested that dietary salt can activate intestinal fibroblasts, thereby contributing to exacerbation of intestinal fibrosis. Dietary salt may be considered as a putative environmental factor that drives intestinal fibrosis risk.

Resume Introduction Les carcinomes de l’endometre de type 2 sont des cancers peu frequents et de mauvais pronostique. Il existe tres peu d’etude analysant leur prise en charge. L’objectif de l’etude etait d’etudier la prise en charge des carcinomes de type 2 dans nos centres en evaluant l’application des recommandations. Materiel et methode Il s’agit d’une etude multicentrique retrospective enregistrant les cancers de l’endometre de type 2 pris en charge de janvier 2009 a decembre 2019. Les analyses ont ete adaptees aux dernieres recommandations francaises appliquees par rapport a l’annee de prise en charge. Resultats Soixante-quatorze carcinomes de type 2 ont ete analyses dans dix centres: 34 carcinosarcomes (45,9 %), 29 carcinomes sereux (39,2 %), neuf carcinomes a cellules claires (12,2 %) et deux carcinomes indifferencies (2,7 %). Lors de la prise en charge initiale, les recommandations etaient appliquees dans 45,9 % des cas. Le principal motif de non-application des recommandations etait la non-realisation d’une stadification ganglionnaire chirurgicale pour 20 patientes (57,1 %). Lors de la prise en charge adjuvante, les recommandations etaient appliquees dans 37,8 % des cas. Le principal motif de non-application des recommandations etait la non-realisation d’une restadification ganglionnaire chirurgicale ou radiologique pour 25 patientes (67,6 %). Discussion L’applicabilite des recommandations pour la prise en charge des carcinomes de type 2 reste difficile en raison de l’âge eleve et des comorbidites des patientes notamment pour la realisation d’une stadification chirurgicale ganglionnaire pelvienne et lombo-aortique. L’utilisation de nouvelles techniques de stadification permettrait de mieux selectionner les indications de curages ganglionnaires.

Undernutrition is a global health issue leading to 1 out 5 all deaths in children under 5 years. Undernutrition is often associated with environmental enteric dysfunction (EED), a syndrome associated with increased intestinal permeability and gut inflammation. We aimed to develop a novel murine model of undernutrition with these EED features. Post-weaning mice were fed with low-protein diet (LP) alone or combined with a gastrointestinal insult trigger (indomethacin or liposaccharides). Growth, intestinal permeability and inflammation were assessed. LP diet induced stunting and wasting in post-weaning mice but did not impact gut barrier. We therefore combined LP diet with a single administration of indomethacin or liposaccharides (LPS). Indomethacin increased fecal calprotectin production while LPS did not. To amplify indomethacin effects, we investigated its repeated administration in addition to LP diet and mice exhibited stunting and wasting with intestinal hyperpermeability and gut inflammation. The combination of 3-weeks LP diet with repeated oral indomethacin administration induced wasting, stunting and gut barrier dysfunction as observed in undernourished children with EED. As noninvasive methods for investigating gut function in undernourished children are scarce, the present pre-clinical model provides an affordable tool to attempt to elucidate pathophysiological processes involved in EED and to identify novel therapeutic strategies.

Endometrial osseous metaplasia (EOM) is a rare condition characterised by the presence of bone in the uterine cavity. Some patients with this condition present with secondary infertility due to the presence of a foreign body in the endometrium. We report a case of a 39-year-old woman who presented with secondary infertility due to EOM. EOM is a rare cause of infertility that can be easily managed by hysteroscopic removal of the bony fragments.

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.

Endometrial osseous metaplasia (EOM) is a rare condition characterised by the presence of bone in the uterine cavity. Some patients with this condition present with secondary infertility due to the presence of a foreign body in the endometrium. We report a case of a 39-year-old woman who presented with secondary infertility due to EOM. EOM is a rare cause of infertility that can be easily managed by hysteroscopic removal of the bony fragments.

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.

AIM To assess the feasibility of SPECT-computed tomography (CT) in rats with trinitrobenzene sulfonic acid (TNBS)-induced acute colitis and confront it with model inflammatory characteristics. METHODS Colitis was induced in Sprague-Dawley rats by intrarectal injection of TNBS (n = 10) while controls received vehicle (n = 10). SPECT-CT with intravenous injection of 10 MBq of 67Ga-Citrate was performed at day 2. SPECT-CT criteria were colon wall thickness and maximal wall signal intensity. Laboratory parameters were assessed: colon weight:length ratio, colon cyclooxygenase-2 expression by western blot and histological inflammatory score. RESULTS Colon weight/length ratio, colon COX-2 expression and histological inflammatory score were significantly higher in the TNBS group than in the control group (P = 0.0296, P < 0.0001, P = 0.0007 respectively). Pixel max tend to be higher in the TNBS group than in the control group but did not reach statistical significance (P = 0.0662). Maximal thickness is significantly increased in the TNBS group compared to the control group (P = 0.0016) while colon diameter is not (P = 0.1904). Maximal thickness and colon diameter were correlated to colon COX-2 expression (P = 0.0093, P = 0.009 respectively) while pixel max was not (P = 0.22). Maximal thickness was significantly increased when inflammation was histologically observed (P = 0.0043) while pixel max and colon diameter did not (P = 0.2452, P = 0.3541, respectively). CONCLUSION SPECT-CT is feasible and easily distinguished control from colitic rats.

Irritable bowel syndrome is a multifactorial disease. Although faecal calprotectin has been shown to be a reliable marker of intestinal inflammation, its role in irritable bowel syndrome remains debated.The aims of this prospective study were to select a subgroup of irritable bowel syndrome patients and to characterise those patients with high faecal calprotectin by systematic work-up.Calprotectin levels were determined by enzyme-linked immunosorbent assay test in consecutive irritable bowel syndrome patients fulfilling Rome III criteria in whom normal colonoscopy and appropriate tests had excluded organic disease. Calprotectin levels were compared in irritable bowel syndrome patients, healthy controls and patients with active and quiescent Crohn's disease. When the calprotectin level was higher than 50 µg/g, the absence of ANCA/ASCA antibodies and a normal small bowel examination were required to confirm irritable bowel syndrome diagnosis. Additional explorations included assessment of irritable bowel syndrome severity, anxiety and depression, impact on quality of life, glucose and fructose breath tests, rectal distension test by barostat and quantitative and qualitative assessment of inflammation on colonic biopsies.Among the 93 irritable bowel syndrome patients (73% women; 66.7% with diarrhoea) recruited, 34 (36.6%) had reproducibly elevated calprotectin. Although they tended to be older than those with normal calprotectin (Elevated faecal calprotectin was observed in one third of patients in this series, without any significant association with a specific clinical phenotype (except age) or specific abnormalities.

Objective To evaluate the impact of bowel occult microscopic endometriosis (BOME) implants on postoperative outcomes in patients treated with colorectal resection for deep infiltrating digestive endometriosis. Design Prospective series of consecutive patients with deep colorectal endometriosis managed by colorectal resection in our department from June 2009 to November 2014 and enrolled in the CIRENDO database (NCT02294825). Setting University tertiary referral center. Patient(s) One hundred three patients managed by colorectal resection for deep infiltrating endometriosis. Intervention(s) Histologic examination of colorectal resection specimens. Main Outcome Measure(s) Patient characteristics, preoperative and 1-year postoperative symptoms and intraoperative findings were compared between women with and without BOME on specimen resection margins. Result(s) In 15 cases, BOME was found in one (nine cases) or both resection limits (six cases). No statistical significance was found between BOME and height of colorectal anastomosis, length of the resected bowel specimen or depth of rectal wall infiltration. One patient with BOME underwent a second colorectal resection 5 years later for rectal recurrence. Comparison between the rates of dyschezia, diarrhea, constipation, bloating and overall values of GIQLI and KESS scores 1 and 3 years postoperatively showed no statistical significance between women with and without BOME. Conclusion(s) BOME was found in 14.6% of specimen resection margins. No impact on either pelvic or digestive symptoms was observed after 1-year follow-up postoperatively. Clinical Trial Registration Number NCT02294825.

Objective To provide a mapping of bowel occult microscopic endometriosis implants from colorectal specimens removed from patients who had undergone colorectal resection for deep endometriosis infiltrating the rectum. Design A series of consecutive patients with deep endometriosis infiltrating the rectum or/and sigmoid colon, between January 2013 and December 2013. Setting University tertiary referral center. Patient(s) Twenty-six patients with deep endometriosis infiltrating the rectum or/and sigmoid colon. Intervention(s) Surgical management by colorectal resection. Main Outcome Measure(s) Twenty-six patients with prospective recording of data (age, clinical history, symptoms, preoperative assessment, and intraoperative findings) underwent colorectal resection for bowel endometriosis. Mapping of occult microscopic endometriosis implants from specimens was established by histologic examination of 1,051 microsection slides taken from transversal macrosections of 3-mm thickness (40 microsections per patient on average). Result(s) The mean (SD) length of colorectal specimens was 110 (42) mm. Microimplants were found at varying distances up to 54 mm from macronodule limits. Multiple macroscopic nodules were identified in five patients (19.2%). In 18 specimens (69%) diffusion of endometriosis microimplants was longitudinal, whereas in 8 specimens (31%) diffusion was concentrated around the macroscopic nodule. Respectively, 31%, 19%, 8%, and 4% of patients presented with endometriosis microimplants at 2, 3, 4, and 5 cm from macroscopic nodules. Conclusion(s) The present data suggest that in patients presenting with deep colorectal endometriosis, microscopically complete excision of rectal endometriosis may be unachievable because of bowel occult microscopic endometriosis implants located far from macroscopic nodules.

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.

Anticancer chemotherapy often induces side effects such as mucositis. Recent data suggest that a diet, Clinutren Protect (CP), containing whey proteins, glutamine, and transforming growth factor-b (TGFb)-rich casein limits intestinal mucositis and improves recovery after a single methotrexate (MTX) challenge in rats. Chemotherapy consists of alternating periods of treatment and rest. Thus, our study evaluated the effects of CP on nutritional outcome and intestinal mucositis in rats receiving repeated chemotherapeutic challenges. Thirty-six Sprague-Dawley rats received 3 cycles of MTX at 8-d intervals. Rats had free access to CP or control diet (Co) from 7 d before the first MTX injection until the end of the experiment at d 27. In Co, whey proteins and TGFb-rich casein were replaced by TGFb-free casein. L-Glutamine was replaced by L-alanine. Body composition was assessed by dual energy X-ray absorptiometry. Before MTX challenges, food intake and body weight were similar in both groups but became higher during MTX challenges in CP (P , 0.05). Fat mass decreased similarly in both groups. In contrast, the decrease of fat free mass between d 21 and d 27 was less pronounced in the CP group (29.5 g) than in the Co group (257.2 g) (P , 0.05). The intestinal damage score was lower in the CP group (0.6 6 0.3 vs. 2.1 6 0.6; P , 0.05). Fecal IgA increased over time in the CP group (P , 0.05) but not in the Co group. A diet containing whey proteins, glutamine, and TGFb improves nutritional outcome by limiting the reduction of fat free mass and reduces intestinal mucositis during repeated chemotherapeutic challenges in rats. J. Nutr. 140: 799‐805, 2010.

Study Objective To document the presence of bowel invisible microscopic endometriosis implants and their relationship with deep endometriosis macronodule infiltrating the bowel. Design A series of consecutive patients with deep endometriosis infiltrating the rectum and/or sigmoid colon (Canadian Task Force classification II-2). Settings A university referral center. Patients Ten patients managed by colorectal resection. Interventions A microscopic study of endometriotic foci of the bowel involving 3272 microsection slides was established using a unique method of step serial sections using combined transverse and longitudinal macrosection. Two-dimensional reconstruction based on slide scanning highlighted the presence and localization of the deep endometriosis macronodule in contrast with bowel invisible microscopic endometriosis microimplants. Measurements and Main Results The distance separating the microimplants and the nodule and their histologic characteristics. The mean length of the colorectal specimens was 91 ± 19 mm. The maximum distance between the farthest microimplants was 7.2 cm. The maximum distance from the macroscopic nodule limit to the farthest microimplant was 31 mm. Bowel invisible microscopic endometriosis microimplants presented with similar features independently of the type of spread. They had an active appearance including stroma and glands, were sometimes decidualized, and were free of fibrosis. They were found on the distal/rectal limit of the specimen in 3 patients and on both limits (distal/rectal and proximal/sigmoid colon) in 1 patient. Conclusion Invisible microscopic endometriosis implants surround the bowel macroscopic endometriosis nodule at variable distances, suggesting that complete surgical microscopic removal may be a challenging goal. These results may help to reconsider the principles and feasibility of the surgical management of bowel endometriosis.

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Summary Background & aims Increased intestinal permeability occurs during chemotherapy-induced intestinal mucositis. Previous data suggest that glutamine and arginine may have additive or synergic effects to limit intestinal damage. The present study aimed to evaluate the effects of glutamine and arginine, each alone or in combination, on gut barrier function during methotrexate (MTX)-induced mucositis in rats. Methods Eighty Sprague Dawley rats received during 7 days (d) standard chow supplemented with protein powder (PP), glutamine (G, 2%), arginine (A, 1.2%) or glutamine plus arginine (GA). All diets were isonitrogenous. Rats received subcutaneous injections of MTX (2.5 mg/kg) from d0 to d2. The intestinal permeability and tight junction proteins were assessed at d4 and d9 in the jejunum by FITC-dextran and by western blot and immunohistochemistry, respectively. Results At d4, intestinal permeability was increased in MTX-PP, MTX-A and MTX-GA rats compared with controls but not in MTX-G rats. The expression of claudin-1, occludin and ZO-1 was decreased in MTX-PP group compared with controls but was restored in MTX-G and MTX-A rats. In MTX-GA rats, occludin expression remained decreased. These effects could be explained by an increase of erk phosphorylation and a decrease of IκBα expression in MTX-PP and MTX-GA rats. At d9, Intestinal permeability remained higher only in MTX-GA rats. This was associated with a persistent decrease of occludin expression. Conclusions Glutamine prevents MTX-induced gut barrier disruption by regulating occludin and claudin-1 probably through erk and NF-κB pathways. In contrast, combined glutamine and arginine has no protective effect in this model.

Cartilage-hair-hypoplasia is a rare autosomal recessive metaphyseal dysplasia due to RMRP (the RNA component of the RNase MRP ribonuclease mitochondrial RNA processing complex) gene mutations. So far, about 100 mutations have been reported in the promoter and the transcribed regions. Clinical characteristics include short-limbed short stature, sparse hair and defective cell-mediated immunity. We report herein the antenatal presentation of a female foetus, in whom CHH was suspected from 23 weeks' gestation, leading to a medical termination of the pregnancy at 34 weeks gestation, and thereafter confirmed by morphological and molecular studies. Post-mortem examination confirmed short stature and limbs, and revealed thymic hypoplasia associated with severe CD4 T-cell immunodeficiency along with extensive non caseating epithelioid granulomas in almost all organs, which to our knowledge has been described only in five cases. Molecular studies evidenced on one allele the most frequently reported founder mutation NR_003051: g.70A>G, which is present in 92% of Finnish patients with Cartilage Hair Hypoplasia. On the second allele, a novel mutation consisting of a 10 nucleotide insertion at position −18 of the promoter region of the RMRP gene ( M29916.1 :g.726_727insCTCACTACTC) was detected. The founder mutation was inherited from the father, and the novel mutation from the mother. To our knowledge, this case report represents the first detailed foetal analysis described in the literature.

Magnetic resonance colonography (MRC) has been recently developed to assess bowel inflammation in inflammatory bowel disease (IBD) patients. Evaluating animal models of inflammation with MRC may be important in new drug-screening processes. The aim of this study was to assess the feasibility of MRC in colitic rats and confront it with model characteristics.Colitis was induced by rectal injection of trinitrobenzene-sulfonic acid (TNBS) in 13 rats while six rats received the vehicle. MRC was performed at day 2. Colon inflammation and production of inflammatory mediators were evaluated. Image quality was assessed by wall and motion artifacts. MRC criteria were bowel wall thickness, wall signal intensity on T2-weighted (T2w) and T1w images, the appearance of a target sign pattern, and irregular patterns of mucosal surface.MRC quality was good or excellent in 16/21 examinations with no difference between groups. Colitis rats were significantly different from controls in terms of wall thickness (P = 0.004), the appearance of a target sign pattern (P = 0.02), irregular patterns of mucosal surface (P = 0.01), and hyperintensity on T1w images (P = 0.03). All MRC criteria except maximal bowel wall thickness were associated with colon weight:length ratio and inflammatory biomarkers (all P0.05). Minimal bowel wall thickness and wall signal intensity on T2w images were associated with histological score (P0.05).MRC is feasible and reliable in rats with TNBS-induced colitis. MRC criteria including colon wall thickness, wall signal intensity on T2w images, hyperintensity in T1w sequence, and the appearance of a target sign pattern may be potential targets for new IBD drugs.

5-aminosalicylic acid (5-ASA) is widely used for the treatment of inflammatory bowel disease (IBD). Recent studies have evaluated the potential of nutritional intervention as adjunct therapy to 5-ASA in IBD. N-3 polyunsaturated fatty acids (PUFA) have shown potent anti-inflammatory properties in gut inflammation. Therefore, we aimed to evaluate the efficacy of the dual therapy (n-3 PUFA plus 5-ASA) in rats with 2, 4, 6-trinitrobenzen sulfonic acid (TNBS)-induced colitis. Colitis was induced by intrarectal injection of TNBS while control rats received the vehicle. Rats received by gavage a fish oil-rich formula (n-3 groups) or an isocaloric and isolipidic oil formula supplemented with 5-ASA for 14 days. A dose response of 5-ASA (5-75 mg. suppression mg kg(-1) d(-1)) was tested. Colitis was evaluated and several inflammatory markers were quantified in the colon. COX-2 expression (P

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.

To investigate whether targeting proteasome might reverse intestinal fibrosis in rats.Chronic colitis was induced in rats by repeated administration of increasing dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 15, 30, 45, 60, 60, 60 mg) by rectal injection for 6 wk (from day 0 to day 35), while control rats received the vehicle. TNBS + bortezomib (BTZ) rats received intraperitoneal injections of BTZ twice weekly (from day 37 to day 44) at a dose of 25 mg/kg, whereas the control and TNBS groups received the same amount of the vehicle. Histologic scoring of inflammation and fibrosis was performed. Colonic production of transforming growth factor (TGF)-β was measured by ELISA. Colon fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, Akt and peroxisome proliferator activated receptor γ (PPARγ) were studied by western blot. Expression of the tight junction proteins, occludin and claudin-1, were assessed by Western blot. Colon proteasome activities (chymotrypsin-like and trypsin-like activities) were assessed.TNBS-treated rats had a higher colon weight/length ratio compared to control rats (P0.01). Furthermore, fibrosis and inflammation scores were higher in TNBS-treated rats compared to control rats (P0.01 for both). Colonic production of TGF-β production tended to be higher in TNBS-treated rats (P0.06). Fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, and PPARγ were significantly higher in TNBS-treated rats compared to control rats (all P0.05). TNBS rats had a higher expression of Akt compared to control rats (P0.01). Tight junction proteins were modified by repeated TNBS challenge: colon occludin expression rose significantly (P0.01), whereas claudin-1 expression fell (P0.01). Bortezomib inhibition significantly decreased chymotrypsin-like activity (P0.05), but had no significant effect on trypsin-like activity (P0.05). In contrast, bortezomib had no effect on other studied parameters such as fibrosis score, TGF-β signaling, or tight junction expression (P0.05 for all).Rats with TNBS-induced chronic colitis exhibited colon fibrosis associated with higher TGF-β signaling. Proteasome inhibition by bortezomib had no effect on fibrosis in our experimental conditions.