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Saint-Clément-de-la-Place, France

Diemunsch P.A.,Hopitaux Universitaires | Noll E.,Hopitaux Universitaires | Pottecher J.,Hopitaux Universitaires | Diana M.,IRCAD EITS | And 2 more authors.
European Journal of Anaesthesiology | Year: 2016

BACKGROUND Nitrous oxide (N 2 O) is still considered an important component of general anaesthesia. However, should gas embolisation occur as result of carbon dioxide (CO 2) pneumoperitoneum, N 2 O may compromise safety, as the consequences of a gas embolus consisting of a combination of CO 2 and N 2 O may be more severe than CO 2 alone. OBJECTIVE This experimental study was designed to compare the cardiopulmonary consequences of gas embolisation with a N 2 O/CO 2 mixture, or CO 2 alone. DESIGN Experimental study. SETTING Research Institute Against Digestive Cancer laboratory, Strasbourg, France. ANIMALS Seven Large-White pigs receiving standardised inhalation anaesthesia. INTERVENTIONS Each animal, acting as its own control, was studied in two successive experimental conditions - intravenous gas injections of 2-ml-kg -1 of 100% CO 2 and 2-ml-kg -1 of a gas mixture consisting of 10% N 2 O and 90% CO 2. MAIN OUTCOMES MEASURES Haemodynamic and ventilatory consequences of embolisation with the gases. RESULTS We found that the haemodynamic (heart rate, mean arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure and transoesophageal echocardiography parameters) and ventilatory (arterial oxygen saturation, end-tidal CO 2 concentration and mixed venous oxygen saturation) consequences of embolisation with either 100% CO 2 or 10% N 2 O with 90% CO 2 were similar. CONCLUSION The findings of this study may alleviate concerns that the use of N 2 O, as a part of a balanced general anaesthesia technique, may have greater adverse consequences should embolisation of pneumoperitoneal gas containing N 2 O occur. © 2016 European Society of Anaesthesiology.

Kauntz H.,University of Strasbourg | Bousserouel S.,University of Strasbourg | Gosse F.,University of Strasbourg | Marescaux J.,IRCAD EITS | Raul F.,University of Strasbourg
International Journal of Oncology | Year: 2012

The flavonolignan silibinin, the major biologically active compound of the milk thistle (Silybum marianum), has been shown to possess anticancer properties in a variety of epithelial cancers. The present study investigated the potential of silibinin as a chemopreventive agent in colon carcinogenesis. The rat azoxymethane (AOM)-induced colon carcinogenesis model was used because of its molecular and clinical similarities to sporadic human colorectal cancer. One week after AOM injection (post-initiation), Wistar rats received daily intragastric feeding of 300 mg silibinin/kg body weight per day until their sacrifice after 7 weeks of treatment. Silibinin-treated rats exhibited a 2-fold reduction in the number of AOM-induced hyperproliferative crypts and aberrant crypt foci in the colon compared to AOM-injected control rats receiving the vehicle. Silibinin-induced apoptosis in the colon mucosal cells was demonstrated by flow cytometry after propodium iodide staining and by colorimetric measurement of caspase-3 activity. Mechanisms involved in silibinin-induced apoptosis included the downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the pro-apoptotic protein Bax, inverting the Bcl-2/Bax ratio to <1. This modulation already takes place at the mRNA expression level as shown by real-time RT-PCR. Furthermore, silibinin treatment significantly (P<0.01) decreased the genetic expression of biomarkers of the inflammatory response such as IL1β, TNFα and their downstream target MMP7, all of them shown to be upregulated during colon carcinogenesis. The downregulation of MMP7 protein was confirmed by western blot analysis. The present findings show the ability of silibinin to shift the disturbed balance between cell renewal and cell death in colon carcinogenesis in rats previously injected with the carcinogen AOM. Silibinin administered via intragastric feeding exhibited potent pro-apoptotic, anti-inflammatory and multi-targeted effects at the molecular level. The effective reduction of preneoplastic lesions by silibinin supports its use as a natural agent for colon cancer chemoprevention.

Sananes N.,Strasbourg Teaching Hospital | Sananes N.,French Institute of Health and Medical Research | Ruano R.,Baylor College of Medicine | Weingertner A.-S.,Strasbourg Teaching Hospital | And 12 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2015

Objective: The monkey model is the best model to investigate some physiological response to the fetal transitory tracheal occlusion but it has never been described in Macaca monkeys. The aim of this study was to evaluate the feasibility of fetal endoscopic tracheal occlusion (FETO) in a non-human primate model. Methods: Pregnant rhesus monkeys and cynomolgus were tested as a potential experimental model for FETO in the third trimester of pregnancy, by performing fetal tracheoscopies with and without tracheal occlusion. Results: A total of 22 pregnancies were followed in 16 monkeys and underwent fetal surgery. Percutaneous endoscopic access to the uterine cavity was possible in 20 cases (91%). Of these 20 pregnant monkeys, fetal tracheoscopy could be achieved in 15 cases (75%). In rhesus monkeys, the time between the onset of endoscopy and tracheal penetration decreases as operator experience increases. Neither maternal morbidity nor mortality was related to surgery. Two fetal losses were possibly due to the procedure. Conclusion: FETO is feasible in the non-human primate, which closely reflects procedures in humans. The non-human primate model for FETO, specially the rhesus monkeys, may be useful for future studies concerning the mechanisms related to the lung growth after transitory fetal tracheal occlusion. © 2014 Informa UK Ltd. All rights reserved.

Cahill R.A.,European Institute of Surgical Research of Innovation | Asakuma M.,IRCAD EITS | Trunzo J.,Case Western Medical Center | Schomisch S.,Case Western Medical Center | And 5 more authors.
Journal of Gastrointestinal Surgery | Year: 2010

Introduction: Fibered optical coherence tomography (OCT) in conjunction with natural orifice transluminal endoscopic surgery (NOTES) could provide a facility for rapid, in situ pathological diagnosis of intraperitoneal tissues in a truly minimally invasive fashion. Materials and Methods: A large porcine model was established to test this hypothesis. A standard double channel gastroscope (Olympus) was used to achieve a transgastric access to the peritoneum and initiate the pneumoperitoneum. Magnetic retraction was used to display the sigmoid colon along with its mesentery. A commercially available fibered OCT probe (NIRIS system, Imalux) was inserted via a working channel of the gastroscope and used to assess intraperitoneal tissues. Separately, OCT images of human tissue specimens ex vivo were contrasted with representative standard histopathological slides. Results: Intraperitoneal OCT provided clear real-time images of both the serosal and muscularis propria mural layers as well as the submuscosal-muscularis interface. Examination of mesenteric lymph nodes (including sentinel nodes) allowed visualization of their subcapsular sinus. Comparison of representative cross-sections however failed to evince sufficient resolution for confident diagnosis. Conclusion: This approach is technically feasible and, if the technology is advanced and proven accurate in human patients, could potentially be used to individualize operative extent prior to definitive resection. © 2009 The Society for Surgery of the Alimentary Tract.

Bousserouel S.,University of Strasbourg | Kauntz H.,University of Strasbourg | Gosse F.,University of Strasbourg | Bouhadjar M.,IRCAD EITS | And 3 more authors.
International Journal of Oncology | Year: 2010

The rat azoxymethane (AOM)-induced colon carcinogenesis model provides useful information for understanding human colorectal neoplasia. Here, we used the AOM model to measure the gene expression profiles of biomarkers related to tumor progression. We assessed tumor progression stages by computed tomographic (CT) colonography. Messenger RNAs were isolated from tumors and mucosal samples, and gene expression levels were assessed by real-time quantitative polymerase chain reaction (PCR). We show that early stages of tumor progression are associated with an upregulation of matrix metalloproteinase-7 (MMP-7) and of genes involved in the inflammatory response, including interleukin (IL1β) and tumor necrosis factor-α (TNFα). The ratio of B-cell lymphoma/leukemia 2 (Bcl-2)-associated X proteins (Bax) to Bcl-2 transcript (proapototic/antiapoptotic signals) is elevated in early stages of tumor progression (Bax/Bcl-2 >1) and reversed in more advanced stages of tumor development (Bax/Bcl-2 <1). These changes are associated with the reduced expression of TNF-related apoptosis-inducing ligand (TRAIL)-death receptor 5 (DR5) and FAS (also known as CD95) apoptotic receptors. Advanced stages of tumor development are characterized by an increase in MMP-9 expression associated with the upregulation of components of the innate immune system: α-defensin 5 (DEF-5) and neutrophil gelatinase-associated lipocalin (NGAL). The identification of specific gene expression profiles that correlate with tumor progression stages, as reported in the present study, may represent an important step in evaluating potential chemopreventive and/or chemotherapeutic agents prior to initiating clinical trials.

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