Jean Michel Fabre

Bio: Jean Michel Fabre is an academic researcher from University of Montpellier. The author has contributed to research in topics: Sleeve gastrectomy & Gastrectomy. The author has an hindex of 18, co-authored 28 publications receiving 893 citations. Previous affiliations of Jean Michel Fabre include French Institute of Health and Medical Research.

The small heterodimer partner interacts with the pregnane X receptor and represses its transcriptional activity.

Abstract: SHP (small heterodimer partner, NR1I0) is an atypical orphan member of the nuclear receptor subfamily in that it lacks a DNA-binding domain. It is mostly expressed in the liver, where it binds to and inhibits the function of nuclear receptors. SHP is up-regulated by primary bile acids, through the activation of their receptor farnesoid X receptor, leading to the repression of cholesterol 7alpha-hydroxylase (CYP7alpha) expression, the rate-limiting enzyme in bile acid production from cholesterol. PXR (pregnane X receptor, NR1I2) is a broad-specificity sensor that recognizes a wide variety of synthetic drugs as well as endogenous compounds such as bile acid precursors. Upon activation, PXR induces CYP3A and inhibits CYP7alpha, suggesting that PXR can act on both bile acid synthesis and elimination. Indeed, CYP7alpha and CYP3A are involved in biochemical pathways leading to cholesterol conversion into primary bile acids, whereas CYP3A is also involved in the detoxification of toxic secondary bile acid derivatives. Here, we show that PXR is a target for SHP. Using pull-down assays, we show that SHP interacts with both murine and human PXR in a ligand-dependent manner. From transient transfection assays, SHP is shown to be a potent repressor of PXR transactivation. Furthermore, we report that chenodeoxycholic acid and cholic acid, two farnesoid X receptor ligands, induce up-regulation of SHP and provoke a repression of PXR-mediated CYP3A induction in human hepatocytes as well as in vivo in mice. These results reveal an elaborate regulatory cascade, tightly controlled by SHP, for both the maintenance of bile acid production and detoxification in the liver.

Impact of Laparoscopic Sleeve Gastrectomy and Laparoscopic Gastric Bypass on HbA1c Blood Level and Pharmacological Treatment of Type 2 Diabetes Mellitus in Severe or Morbidly Obese Patients. Results of a Multicenter Prospective Study at 1 Year

Abstract: Gastric bypass (GBP) has proved its efficacy 30 years ago in the management of diabetes mellitus (T2DM) for severe obese patients. More recently, interesting results have been published after sleeve gastrectomy (SG) in the same indication. Between 2005 and 2008, three bariatric centers have prospectively collected the data of T2DM patients treated by laparoscopic gastric bypass (LGBP) or laparoscopic sleeve gastrectomy (LSG). Effects on hemoglobin A1c (HbA1c), pharmacological treatment and excess weight loss after 1 year of surgery have been analyzed. All patients (35 LGBP and 33 LSG) were treated with oral anti-diabetics (OAD) or insulin before surgery (32 OAD and three insulin in LGBP group and 27 OAD and six insulin in LSG group). The average body mass index (BMI) in the LGBP group was 47.9 and 50.6 kg/m² in the LSG group. At 1 year after surgery, the average HbA1c lost was 2,537 in the GBP group and 2,175 in the SG group. T2DM had resolved (withdrawal of pharmacological treatment) in 60% of the LGBP group and 75.8% of the LSG group. Reduced use of pharmacological therapy was noted in 31.42% of the LGBP group and 15.15% of the LSG group. Percentage excess weight loss and BMI lost were 56.35% and 29.75% in the LGBP group and 60.11% and 29.80% in the LSG group, respectively. During short-term follow-up, the impact on regulation of HbA1c blood level of LGBP or LSG is important. At 1 year after surgery, LSG seems to be as effective as LGBP for the management of T2DM in severely obese patients.

Improvement in Quality of Life After Laparoscopic Sleeve Gastrectomy

Abstract: Few studies have investigated changes in health-related quality of life (HRQOL) in surgical patients who have undergone a laparoscopic sleeve gastrectomy. Prospective data were obtained from 78 consecutive patients undergoing laparoscopic sleeve gastrectomy (LSG; mean age, 42.4 years; mean body weight, 131 kg; mean body mass index (BMI), 47 kg/m(2) (24.4% of superobese patients)). Two HRQOL questionnaires were administered preoperatively and 12 months postsurgery: the generic Medical Outcomes Study Short Form-36 and the weight-specific IWQOL-Lite questionnaire. Excess weight loss at 12 months was 57.18%. No mortality was recorded. HRQOL scores revealed a significant improvement in all areas of both questionnaires. However, changes in HRQOL were not associated consistently with amount of weight loss. Laparoscopic sleeve gastrectomy is an effective and safe procedure, with positive changes in health-related quality of life as well as weight reduction. A fruitful area for future research is the investigation of long-term changes in HRQOL after LSG.

Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient—2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery

Abstract: The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE-TOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues.

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

Abstract: This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.

전자/제조업의 Collaboration 전략

Abstract: Mental health issues often co-occur with other problems such as substance abuse, and they can take an enormous toll on individuals and impact a college or university in many ways. There are staff and departments both onand off-campus who are concerned about the well-being of students and the impact of mental health issues, so partnerships around mental health promotion and suicide prevention make good sense.