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Biomedical subjects

Pierre Dechelotte

Publications and source records attributed to Pierre Dechelotte.

9 recordsLinked to original sources

Molecular and metabolic retinoid pathways in human amniotic membranes.

Vitamin A (retinol) and its active derivatives (the retinoids) are essential for the growth and development of the mammalian fetus and placenta. The amniotic membranes are extra-embryonic structures that are indispensable for normal gestation in mammals. Although placental involvement of retinoids is clearly established, little is known about the roles of retinoids for the associated amniotic membranes. The aim of this study was to define the metabolic and molecular pathways of retinoic signaling in human fetal membranes. The expression of retinoid receptors (RARalpha, beta and RXRalpha, beta) was established at transcript and protein levels. Enzymes involved in retinoic acid generation were also detected. The enzymatic generation of functional retinoids was confirmed using specific inhibitors of retinol metabolism. Finally, the functionality of retinoid pathways was demonstrated by inducing established retinoid target gene expression. Our results clearly demonstrated that the molecular and metabolic actors of retinoic signaling pathways are functional in human fetal membranes.

Amnion↗

Growth arrest and decrease of alpha-SMA and type I collagen expression by palmitic acid in the rat hepatic stellate cell line PAV-1.

Liver fibrosis is characterized by an activation of hepatic stellate cells (HSC). During primary culture HSC evolve from a quiescent into an activated phenotype which is characterized by alpha-smooth muscle actin (alpha-SMA) up-regulation, increase in cell growth, and extracellular matrix secretion. HSC culture with trans-resveratrol can lead to deactivation of myofibroblast-like HSC. We used an HSC line, PAV-1, to check the role of retinol and palmitic acid in the deactivation process of HSC. Using mass and metabolic-based methods, Western blot and immunocytochemistry assays, we demonstrated that treatment with palmitic acid (75 muM) alone or in combination with retinol (2 muM) significantly decreased cell proliferation and alpha-SMA expression. We also established that the association of both compounds strongly decreased collagen type I expression. Our results suggest the potential use of palmitic acid alone or in combination with retinol to induce HSC deactivation.

Actins↗

[Prevention and treatment of undernutrition in hospitals and institutions. Cross-sectional study in 116 health facilities in Haute-Normandie (France), 2003].

INTRODUCTION: The elderly, especially the institutionalized elderly, are at risk of undernutrition, which institutions do not appear to identify or treat adequately. OBJECTIVE: To identify activities undertaken to manage and prevent undernutrition in the elderly in institutions in Haute-Normandy (France). METHODS: In February 2003, all institutions in Haute-Normandy likely to house the elderly received questionnaires for this cross-sectional study: public hospitals (PH) responded, private hospitals (PRH), and retirement homes, classified into two groups according to the medical services provided (RH, retirement homes, NH, nursing homes). RESULTS: Slightly more than half the institutions responded: 34/36 PH, 20/28 PRH, and 62/161 RH and NH. Half Only 22% reported specific protocols for undernutrition; this figure ranged from 30.3% for PH to 13.6% for RH (p=0.22). Patients' food intake was tracked at 67% of the institutions - from 81.8% of the PH to 45.5% of the retirement homes (p=0.10). Meal choices were offered at 54% of the institutions: 85.0% of PRH hospitals offered a choice, but only 45.4% of the PH and of the RH (p=0.01). Overall, 51% asked about eating habits and preferences at admission. Nurses' aides provided help during meals in 46.9% of institutions, and 49% considered they had sufficient staff to help patients during meals: 95.5% in RH, but only 20.7% in PH (p<0.001). DISCUSSION: Institutions for the elderly are well aware of the problems of undernutrition, but not enough of them appear to have a specific protocol to deal with it. Earlier screening for undernourishment would be useful. The study also shows the important role of nurses' aides in this area. CONCLUSION: Institutions in Haute-Normandy agree about the need to screen for and treat undernutrition, but their interventions are not effective. Better organization and special training of health workers could improve this screening and treatment.

Aged↗

Modulation of nitric oxide and cytokines production by L-arginine in human gut mucosa.

BACKGROUND: Arginine is a conditionally essential amino-acid with immuno-modulatory properties, mainly through the nitric oxide (NO) pathway. AIM: To assess the effects of arginine on intestinal production of pro- and anti-inflammatory cytokines and NO in human gut. METHODS: An enteral solution of arginine or a control solution of amino-acids was administered to 8 healthy volunteers on a randomized cross-over design. Duodenal biopsies were taken. Pro- (IL-6, IL-8) and anti-inflammatory (IL-4, IL-10) cytokines mRNA expression was assessed by RT-PCR. Other biopsies were cultured with 0.1, 0.5 or 2 mM arginine or control amino-acids, under basal or IL-1beta-induced inflammatory conditions. Interleukin-4, IL-6, IL-8 and IL-10 production was measured in culture supernatant by ELISA and NO production by Griess reaction. RESULTS: Arginine enhanced the production of NO under inflammatory conditions in a dose-dependent manner (P=0.03). IL-1beta increased the production of IL-8 and IL-6 (P<0.01). Arginine had no effect on pro- and anti-inflammatory cytokines production both under basal and inflammatory conditions. CONCLUSIONS: Arginine enhanced the production of NO but did not affect that of cytokines in inflammatory human gut. Further clinical studies are required to assess whether arginine-enhanced NO production plays a beneficial or deleterious effect in intestinal inflammation.

Adult↗

Rectal instillation of butyrate provides a novel clinically relevant model of noninflammatory colonic hypersensitivity in rats.

BACKGROUND & AIMS: The treatment of irritable bowel syndrome (IBS), characterized by abdominal pain and bloating, is empirical and often poorly efficient. Research lacks suitable models for studying the pathophysiologic mechanisms of the colonic hypersensitivity and new pharmacologic targets. The present study aimed to develop a novel model of colonic hypersensitivity possessing several of the characteristics encountered in patients with IBS. METHODS: Rats received enemas of a butyrate solution (8-1000 mmol/L) twice daily for 3 days. A time course was determined for colonic hypersensitivity (colorectal distention test) and referred cutaneous lumbar hyperalgesia (von Frey hairs). Macroscopic and histologic analyses were performed on colonic mucosa. The efficacy of morphine, U50488H (a kappa opioid agonist), and trimebutine on the 2 pain parameters was determined. Finally, the involvement of peptidergic C-fibers was evaluated using capsaicin-pretreated animals and treatments with calcitonin gene-related peptide (CGRP) and neurokinin 1 receptor antagonists. RESULTS: Butyrate enemas induced a sustained, concentration-dependent colonic hypersensitivity and, to a lesser extent, a referred cutaneous mechanical hyperalgesia, particularly in female rats, but no macroscopic and histologic modifications of the colonic mucosa, as observed in patients with IBS. Both pain parameters were sensitive to morphine, U50488H, trimebutine, neonatal capsaicin treatment, and the CGRP receptor antagonist but not to the neurokinin 1 receptor antagonist. CONCLUSIONS: These results present our noninflammatory model of chronic colonic hypersensitivity as a useful novel tool for studying IBS. The CGRP receptor antagonist-induced reduction of colonic hypersensitivity suggests that CGRP receptors may provide a promising target for treatment of IBS.

Animals↗

Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review.

Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.

Adult↗

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.

Adult↗

Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis.

BACKGROUND: Studies of viral hepatitis C have suggested that fibrosis can regress, at least in patients with sustained virological response. A recent study suggested that cirrhosis was reversible in sustained and non-virological responders. AIM: To study fibrosis progression rate and cirrhosis reversion in patients treated for severe fibrosis with interferon or interferon + ribavirin. PATIENTS AND METHODS: Ninety-nine patients were treated with interferon + ribavirin and 64 with interferon. The Metavir fibrosis score and the semiquantitative fibrosis score (SFS) were used to assess fibrosis. RESULTS: In sustained responders, fibrosis progression rate decreased from 0.26 Metavir unit (interquartile range: 0.19-0.34) to -0.67 (-0.67 to 0) (P < 0.0001) and from 0.81 SFS unit (0.48-1.13) to -1.33 (-3.67 to 0) (P < 0.0001). In non-responders, fibrosis progression rate decreased from 0.25 Metavir unit (0.17-0.33) before treatment to 0 (0-0) during treatment (P = 0.002) and from 0.63 SFS unit (0.49-1.12) to 0 (-2.67-1.33) (P = 0.18). Six out of 18 (33%) sustained virological responders and four of 43 (9%) non-responders regressed from cirrhosis (F4) to severe fibrosis (F3) (P = 0.058). No patient with cirrhosis had a decrease of Metavir fibrosis score of 2 points. CONCLUSION: Interferon can slow fibrosis progression in sustained virological responders with severe fibrosis. In patients with a non-virological response and treated for 12 months the fibrosis progression rate was nil, meaning that only fibrosis stabilization could be obtained in these patients. Then, longer treatment duration (3-4 years) could be evaluated in non-virological responders.

Antiviral Agents↗

Expression of transforming growth factor beta1 in nerve fibers is related to dysmenorrhea and laparoscopic appearance of endometriotic implants.

OBJECTIVE: To quantify the expression of transforming growth factor beta1 in nerve fibers in endometriotic lesions and to correlate it with dysmenorrhea and appearance of endometriotic implants. DESIGN: Prospective comparative study. SETTING: University hospital. PATIENT(S): Peritoneal endometriotic specimens obtained from 35 patients diagnosed with endometriosis were compared with biopsies of normal peritoneum from 10 patients without endometriosis. INTERVENTION(S): Endometriosis-associated dysmenorrhea for each patient was evaluated before surgery using a 10-point visual analog scale, which was followed by a laparoscopic staging of the patient's endometriosis. MAIN OUTCOME MEASURE(S): Immunohistochemical analysis of the peritoneal endometriotic specimens evaluated the maximal intensity of staining (INTMMAX) of TGFbeta1, defined as higher staining intensity found within a selected structure. RESULT(S): When the nerve fibers of endometriotic lesions were compared with those of normal peritoneum, statistically significant differences were found in the INTMMAX of TGFbeta1. Greater TGFbeta1 INTMMAX was found in red lesions and deep endometriotic foci than in black lesions and normal peritoneum. A statistically significant relationship was found between the TGFbeta1 INTMMAX score and dysmenorrhea; a relationship also was found to the color of the lesions. CONCLUSION(S): The physical appearance of endometriotic implants and the severity of dysmenorrhea appear to be related to the expression of TGFbeta1 in nerve fibers.

Adult↗