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See detailLe glucagon-like peptide-1 (GLP-1), nouvelle cible dans le traitement du diabete de type 2.
Scheen, André ULg

in Revue Médicale de Liège (2007), 62(4), 217-21

Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted in response to the ingestion of a meal. It exerts various favourable metabolic effects among which a glucose-dependent stimulation of insulin ... [more ▼]

Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted in response to the ingestion of a meal. It exerts various favourable metabolic effects among which a glucose-dependent stimulation of insulin secretion, an inhibition of glucagon secretion, a slow down of gastric emptying, and a central anorectic effect. In rodents, a protective effect, or even a trophic effect, on B cell has also been reported. Interestingly, GLP-1 secretion is decreased in patients with type 2 diabetes. This observation stimulated the pharmaceutical research with the aim of restoring appropriate GLP-1 circulating levels able to exert the numerous positive effects of the hormone. One of the main objectives was to solve the problem due to the very short half-life of GLP-1. We here briefly describe the main two proposed approaches : ether to subcutaneously inject an incretinomimetic agent closed to GLP-1 (exenatide) or a long-acting GLP-1 analogue (liraglutide), both being partially resistant to the action of dipeptidylpeptidase-IV (DPP-IV), either to orally administer a selective DPP-IV inhibitor, an enzyme metabolising endogenous GLP-1 (sitagliptin, vildagliptin, .... These new drugs offer the advantage of improving blood glucose control of type 2 diabetic patients, without inducing severe hypoglycaemia and without promoting weight gain (instead a weight reduction is generally observed). These agents should occupy a key place in the overall pharmacological strategy of type 2 diabetes in a near future, especially if the additional favourable effects on B cells are confirmed in clinical practice. [less ▲]

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See detailThe glucocorticoid receptor inhibits the human prolactin gene expression by interference with Pit-1 activity
Nalda, Asunción M; Martial, Joseph ULg; Muller, Marc ULg

in Molecular & Cellular Endocrinology (1997), 134(2), 129-37

Glucocorticoids have been shown to inhibit the activity of the human prolactin (hPRL) promoter. Using transient expression experiments in rat pituitary cells, we located the sequence conferring ... [more ▼]

Glucocorticoids have been shown to inhibit the activity of the human prolactin (hPRL) promoter. Using transient expression experiments in rat pituitary cells, we located the sequence conferring glucocorticoid inhibition to a region which contains Pit-1 binding sites, responsible for pituitary-specific expression, but does not seem to contain a glucocorticoid receptor (GR) binding site. Co-transfection experiments in non-pituitary cell lines, using expression vectors for Pit-1 and different mutants of the human GR show that inhibition of the hPRL gene is seen only in the presence of Pit-1 and GR, and that the DNA binding function of the receptor is not required. Immunoprecipitation studies show that either anti-GR or anti-Pit-1 antibodies are able to co-precipitate GR and Pit-1, suggesting an interaction between these factors. We conclude that the activated GR functionally interferes with the pituitary specific factor Pit-1, thereby leading to the observed transcriptional repression. [less ▲]

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See detailThe glucocorticoid receptor.
Muller, Marc ULg; Renkawitz, R.

in Biochimica et Biophysica Acta (1991), 1088

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See detailGlucocorticoid receptors bound to the antagonist RU486 are not downregulated despite their capacity to interact in vitro with defined gene regions
Rajpert, E. J.; Lemaigre, F. P.; Eliard, P. H. et al

in Journal of Steroid Biochemistry (1987), 26(5), 513-20

Modulation of gene expression by glucocorticoids involves interaction of these hormones with an intracellular receptor followed by 'transformation' of the hormone-receptor complex into a nuclear binding ... [more ▼]

Modulation of gene expression by glucocorticoids involves interaction of these hormones with an intracellular receptor followed by 'transformation' of the hormone-receptor complex into a nuclear binding form. The molecular basis for the antiglucocorticoid action of high-affinity steroid analogues such as RU486 remains controversial. The effects of dexamethasone and RU486 on in vitro and in vivo properties of the receptor were compared using human lymphoblastoid IM-9 cells. In these cells, RU486 fully antagonized the glucocorticoid-specific induction of 5'-nucleotidase activity by dexamethasone. In vitro, however, RU486-bound receptor could be transformed and shown to interact specifically with cloned DNA fragments containing glucocorticoid response elements. These fragments included one from the mouse mammary tumour virus and two from the human growth hormone gene. In vivo, RU486-bound receptor did not behave like dexamethasone-bound receptor. While receptor downregulation, a property of the transformed receptor, was achieved by dexamethasone, this did not occur with RU486. Likewise, RU486 did not affect receptor half-life under conditions when this was shortened by dexamethasone. These seemingly contradictory results can be reconciled by proposing that receptor transformation by agonists involves dissociation of the receptor oligomer to reveal a DNA-binding site that pre-exists on this protein. Although cell-free receptor dissociation and therefore DNA binding can occur even when the receptor is bound to RU486, this steroid maintains receptors in the untransformed state in the intact cell and therefore behaves a glucocorticoid antagonist in vivo. [less ▲]

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See detailGlucocorticoid-suppressible hyperaldosteronism and adrenal tumors occurring in a single French pedigree.
Pascoe, L.; Jeunemaitre, X.; LEBRETHON, Marie-Christine ULg et al

in The Journal of clinical investigation (1995), 96(5), 2236-46

Glucocorticoid-suppressible hyperaldosteronism is a dominantly inherited form of hypertension believed to be caused by the presence of a hybrid CYP11B1/CYP11B2 gene which has arisen from an unequal ... [more ▼]

Glucocorticoid-suppressible hyperaldosteronism is a dominantly inherited form of hypertension believed to be caused by the presence of a hybrid CYP11B1/CYP11B2 gene which has arisen from an unequal crossing over between the two CYP11B genes in a previous meiosis. We have studied a French pedigree with seven affected individuals in which two affected individuals also have adrenal tumors and two others have micronodular adrenal hyperplasia. One of the adrenal tumors and the surrounding adrenal tissue has been removed, giving a rare opportunity to study the regulation and action of the hybrid gene causing the disease. The hybrid CYP11B gene was demonstrated to be expressed at higher levels than either CYP11B1 or CYP11B2 in the cortex of the adrenal by RT-PCR and Northern blot analysis. In situ hybridization showed that both CYP11B1 and the hybrid gene were expressed in all three zones of the cortex. In cell culture experiments hybrid gene expression was stimulated by ACTH leading to increased production of aldosterone and the hybrid steroids characteristic of glucocorticoid-suppressible hyperaldosteronism. The genetic basis of the adrenal pathologies in this family is not known but may be related to the duplication causing the hyperaldosteronism. [less ▲]

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See detailLes glucocorticoïdes, de puissants immunomodulateurs naturels
Geenen, Vincent ULg

Conference given outside the academic context (2008)

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See detailGLUCOCORTICOIDS AS DOPING AGENTS IN HOMING PIGEONS
Duchatel, Jean-Pierre ULg; Beduin, Jean-Marie ULg; Jauniaux, Thierry ULg et al

in Annales de Médecine Vétérinaire (1993), 137(8), 557-564

Different commercially available glucocorticoids that could be used to dope racing pigeons have been evaluated using zootechnical and biological parameters. The influence of these corticosteroids on blood ... [more ▼]

Different commercially available glucocorticoids that could be used to dope racing pigeons have been evaluated using zootechnical and biological parameters. The influence of these corticosteroids on blood values have been investigated. Toxicity of triamcinolone diacetate varied proportionally to injected doses and the main effects observed were lymphoid tissue alterations, muscular atrophy with breast muscles fibers vacuolation, fatty degeneration of liver and kidneys, hypoplasia or atrophy of gonads, and, in the blood, a significant increase of calcium and triglycerides levels. Prednisolone acetate in ocular drops was less toxic than dexemathasone and fluocinolone acetonide. The type of corticoids also had an influence on hemoglobin, glucose, and creatinine levels. The inhibition of the molt was also observed and varied with the sort of product used. [less ▲]

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See detailGlucocorticoids Modulate Tumor Radiation Response through a Decrease in Tumor Oxygen Consumption
Crokart, Nathalie; JORDAN, Bénédicte; BAUDELET, Christine et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2007), 15(13), 6305

Purpose: We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO2) through inhibition of mitochondrial respiration. <br /> <br />Experimental Design ... [more ▼]

Purpose: We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO2) through inhibition of mitochondrial respiration. <br /> <br />Experimental Design: The effect of three glucocorticoids (hydrocortisone, dexamethasone, and prednisolone) on pO2 was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO2 (tmax, 30 min after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO2 measurements were done using electron paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo glucocorticoid administration was measured using high-frequency electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging. <br /> <br />Results: All glucocorticoids tested caused a rapid increase in pO2. At tmax, tumor perfusion decreased, indicating that the increase in pO2 was not caused by an increase in oxygen supply. Also at tmax, global oxygen consumption decreased. When irradiation (25 Gy) was applied at tmax, the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7). <br /> <br />Conclusion: These results show the potential usefulness of the administration of glucocorticoids before irradiation. [less ▲]

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See detailGlucoindole alkaloids from stem bark of Strychnos mellodora
Brandt, Viviane; Tits, Monique ULg; Angenot, Luc ULg

Conference (1996, May)

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See detailGlucoindole alkaloids from stem bark of Strychnos mellodora
Brandt, V; Tits, Monique ULg; Angenot, Luc ULg

Poster (1996, February)

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See detailGlucoindole Alkaloids from Stem Bark of Strychnos Mellodora
Tits, Monique ULg; Brandt, V.; Wauters, Jean-Noël ULg et al

in Planta Medica (1996), 62(1), 73-4

Three glucoindole alkaloids, dolichantoside (1), strictosidine (2), and palicoside (3), have been identified in the stem bark of Strychnos mellodora (Loganiaceae), collected in Zimbabwe. The chiroptical ... [more ▼]

Three glucoindole alkaloids, dolichantoside (1), strictosidine (2), and palicoside (3), have been identified in the stem bark of Strychnos mellodora (Loganiaceae), collected in Zimbabwe. The chiroptical (CD) data are compared. [less ▲]

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See detailGlucometer Performance in the Intensive Care Unit
Thomas, Felicity Louise ULg; Pretty, C.P.; Shaw, G.M. et al

Poster (2014)

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See detailGlucosamine and chondroitin salts in the management of osteoarthritis in Europe
Reginster, Jean-Yves ULg

in Osteoporosis International (2015), 26(S1), 60-61

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See detailGlucosamine and chondroitin sulfate as therapeutic agents for knee and hip Osteoarthritis
Bruyère, Olivier ULg; Reginster, Jean-Yves ULg

in Drugs & Aging (2007), 24(7), 573-580

Osteoarthritis (OA), the most common form of arthritis, is a public health problem throughout the world. Several entities have been carefully investigated for the symptomatic and structural management of ... [more ▼]

Osteoarthritis (OA), the most common form of arthritis, is a public health problem throughout the world. Several entities have been carefully investigated for the symptomatic and structural management of OA. This review evaluates published studies of the effect of glucosamine salts and chondroitin sulfate preparations on the progression of knee or hip OA. Despite multiple double-blind, controlled clinical trials of the use of glucosamine and chondroitin sulfate in OA, controversy regarding the efficacy of these agents with respect to symptomatic improvement remains. Several potential confounders, including placebo response, use of prescription medicines versus over-the-counter pills or food supplements, or use of glucosamine sulfate versus glucosamine hydrochloride, may have relevance when attempting to interpret the seemingly contradictory results of different clinical trials. The National Institutes of Health-sponsored GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) compared placebo, glucosamine hydrochloride, chondroitin sulfate, a combination of glucosamine and chondroitin sulfate and celecoxib in a parallel, blinded 6-month multicentre study of patients with knee OA. This trial showed that glucosamine hydrochloride and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with OA of the knee. However, exploratory analyses suggest that the combination of glucosamine hydrochloride and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. For decades, the traditional pharmacological management of OA has been mainly symptomatic. However, in recent years, several randomised controlled studies have assessed the structure-modifying effect of glucosamine sulfate and chondroitin sulfate using plain radiography to measure joint space narrowing over years. There is some evidence to suggest a structure-modifying effect of glucosamine sulfate and chondroitin sulfate. On the basis of the results of recent randomised controlled trials and meta-analyses, we can conclude that glucosamine sulfate (but not glucosamine hydrochloride) and chondroitin sulfate have small-to-moderate symptomatic efficacy in OA, although this is still debated. With respect to the structure-modifying effect, there is compelling evidence that glucosamine sulfate and chondroitin sulfate may interfere with progression of OA. [less ▲]

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See detailGlucosamine and chondroitine sulfate
Reginster, Jean-Yves ULg; Kvasz, Angela ULg; Bruyère, Olivier ULg et al

in Anti Aging Medizin 2001 : Konferenz der German Society of Anti-Aging Medicine (2002)

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See detailGlucosamine sulfate for structure modification in osteoarthritis : fact of fantasy ?
Reginster, Jean-Yves ULg

in Ortopedia, Traumatologia, Rehabilitacja (2011), 13(S1), 44

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See detailGlucosamine sulfate in the treatment of knee osteoarthritis: impact on health utility.
Scholtissen, S.; Bruyère, Olivier ULg; Hiligsmann, Mickaël ULg et al

in Osteoporosis International (2009, March), 20(Suppl.1), 149

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See detailGlucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies
Bruyère, Olivier ULg; Pavelka, K.; Rovati, Lucio C et al

in Menopause (2004), 11(2), 138-143

OBJECTIVE: To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in postmenopausal women with knee osteoarthritis (OA). DESIGN: This study consisted of a ... [more ▼]

OBJECTIVE: To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in postmenopausal women with knee osteoarthritis (OA). DESIGN: This study consisted of a preplanned combination of two three-year, randomized, placebo-controlled, prospective, independent studies evaluating the effect of glucosamine sulfate on symptoms and structure modification in OA and post-hoc analysis of the results obtained in postmenopausal women with knee OA. Minimal joint space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were scored by the algo-functional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed in intention-to-treat, comparing joint space width and WOMAC changes between groups by ANOVA. RESULTS: Of 414 participants randomized in the two studies, 319 were postmenopausal women. At baseline, glucosamine sulfate and placebo groups were comparable for demographic and disease characteristics, both in the general population and in the postmenopausal women subset. After 3 years, postmenopausal participants in the glucosamine sulfate group showed no joint space narrowing [joint space change of +0.003 mm (95% CI, -0.09 to 0.11)], whereas participants in the placebo group experienced a narrowing of -0.33 mm (95% CI, -0.44 to -0.22; P < 0.0001 between the two groups). Percent changes after 3 years in the WOMAC index showed an improvement in the glucosamine sulfate group [-14.1% (95%, -22.2 to -5.9)] and a trend for worsening in the placebo group (5.4% (95% CI, -4.9 to 15.7) (P = 0.003 between the two groups). CONCLUSION: This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA. [less ▲]

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See detailGlucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two large, randomised, placebo-controlled, double-blind, 3-year studies
Bruyère, Olivier ULg; Pavelka, K.; Rovati, Lucio C et al

in Osteoporosis International (2003, November), 14(Suppl. 7), 62

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