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Hôpital-Camfrout, France

Mimoun S.,French National Institute for Agricultural Research | Andriamihaja M.,French National Institute for Agricultural Research | Chaumontet C.,French National Institute for Agricultural Research | Atanasiu C.,Hopital Avicenne | And 5 more authors.
Antioxidants and Redox Signaling | Year: 2012

Aims: Sulfide is released in the large intestine lumen by the microbiota and is an inhibitor of mitochondrial respiration and a genotoxic agent in colonocytes when present in excess. Deciphering how colonocytes metabolize sulfide is an important issue. Results: In this study, using the human colonic epithelial HT-29 Glc-/+ cells, we found that 50 μM sodium hydrogen sulfide represents the threshold of concentration above which respiration is decreased. The capacity of HT-29 Glc-/+ cells to oxidize lower concentration of sulfide was associated with the expression of transcripts corresponding to the enzymes of the sulfide oxidizing unit (SOU), that is, sulfide quinone reductase (SQR), dioxygenase ethylmalonic encephalopathy, and thiosulfate sulfur transferase (TST). Inhibition of cell O2 consumption by sulfide was reverted by zinc but not by calcium and iron. When the cells undergo either spontaneous or butyrate-induced differentiation, their capacity to oxidize sulfide was significantly increased. The expression levels of the genes corresponding to the enzymes of the SOU were not increased, whereas increased cellular maximal respiratory capacity and oxygen consumption by the dioxygenase were both measured. In human biopsies recovered from various parts of the large intestine, the three enzymes of the SOU were expressed. Innovation: SOU and cell respiratory capacity are crucial for sulfide detoxification in colonocytes. Conclusion: Sulfide oxidative capacity in the colonic mucosa is higher in differentiated than in proliferative epithelial cells. The cell respiratory capacity and SOU activity appear to represent major determinants allowing sulfide detoxification in colonic epithelial cells. © 2012 Mary Ann Liebert, Inc. Source

Tallet A.V.,Institute Paoli Calmettes | Azria D.,French Institute of Health and Medical Research | Barlesi F.,Aix - Marseille University | Spano J.-P.,University Paris - Sud | And 3 more authors.
Radiation Oncology | Year: 2012

Whole brain radiation therapy (WBRT) is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests) with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more), insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation. © 2012 Tallet et al.; licensee BioMed Central Ltd. Source

From the organisation of nursing care to the quality of care and the management of human resources, the healthcare manager is the linchpin uniting the different players close to the patient. To ensure this continuity, the healthcare manager relies on a value common to caregivers: the professional conscience. ©2014 Elsevier Masson SAS. All rights reserved. Source

Mourad J.-J.,Hopital Avicenne
Journal of Hypertension | Year: 2011

Fixed-dose combinations have been strongly endorsed by European guidelines for first-line and second-line treatment of hypertension. Among recommended combinations, that of an angiotensin-converting enzyme inhibitor and a calcium channel blocker stands out because the mechanisms of action of these two therapeutic classes are complementary, leading to enhanced efficacy. In the large multicentre ASCOT-BPLA trial, treatment based on the combination of amlodipine and perindopril significantly reduced the risk of cardiovascular and all-cause death, stroke, coronary events and procedures, new-onset diabetes, and new-onset renal impairment in a wide range of patients with hypertension and other cardiovascular risk factors, when compared with atenolol/thiazide-based therapy. The perindopril/amlodipine single-pill combination was developed based on guideline recommendations for combination treatment, the indications of each component, and ASCOT-BPLA trial data. Several studies in real-life settings show that a wide range of hypertensive patients, including everyday hypertensives with common risk factors, would benefit from the perindopril/amlodipine combination. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Ades L.,Hopital Avicenne
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2011

Based on immune mechanisms that appear to play an important role in the pathophysiology of at least part of the lower-risk myelodysplastic syndrome (MDS), the immunomodulating drug (IMID) thalidomide and its derivative lenalidomide (LEN) have been used in MDS, principally in lower-risk MDS. LEN has become the first-line US Food and Drug Administration (FDA)-approved treatment for lower-risk MDS with 5q deletion (del5q), in which its main mechanism of action is probably a direct cytotoxic activity on the del5q clone. This possibly specific effect is currently being investigated in higher-risk MDS-and even acute myeloid leukemia (AML)-with del5q, but LEN has also demonstrated some efficacy in MDS and AML without del5q. Thalidomide also has some activity in lower-risk MDS without del5q, but its side effects limit its practical use in these patients. Source

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