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See detailDrug-delivery implants : Pharmaceutical advantages and current processing technologies
Champeau, Mathilde; Jérôme, Christine ULg; Tassaing, Thierry

Scientific conference (2014, February 25)

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See detailDrug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide.
Scheen, André ULg

in Clinical Pharmacokinetics (2007), 46(2), 93-108

This review describes the current knowledge on drug-drug and food-drug interactions with repaglinide and nateglinide. These two meglitinide derivatives, commonly called glinides, have been developed for ... [more ▼]

This review describes the current knowledge on drug-drug and food-drug interactions with repaglinide and nateglinide. These two meglitinide derivatives, commonly called glinides, have been developed for improving insulin secretion of patients with type 2 diabetes mellitus. They are increasingly used either in monotherapy or in combination with other oral antihyperglycaemic agents for the treatment of type 2 diabetes. Compared with sulfonylureas, glinides have been shown to (i) provide a better control of postprandial hyperglycaemia, (ii) overcome some adverse effects, such as hypoglycaemia, and (iii) have a more favourable safety profile, especially in patients with renal failure.The meal-related timing of administration of glinides and the potential influence of food and meal composition on their bioavailability may be important. In addition, some food components (e.g. grapefruit juice) may cause pharmacokinetic interactions. Because glinides are metabolised via cytochrome P450 (CYP) 3A4 isoenzyme, they are indeed exposed to pharmacokinetic interactions. In addition to CYP3A4, repaglinide is metabolised via CYP2C8, while nateglinide metabolism also involves CYP2C9. Furthermore, both compounds and their metabolites may undergo specialised transport/uptake in the intestine, another source of pharmacokinetic interactions. Clinically relevant drug-drug interactions are those that occur when glinides are administered together with other glucose-lowering agents or compounds widely coadministered to diabetic patients (e.g. lipid-lowering agents), with drugs that are known to induce (risk of lower glinide plasma levels and thus of deterioration of glucose control) or inhibit (risk of higher glinide plasma levels leading to hypoglycaemia) CYP isoenzymes concerned in their metabolism, or with drugs that have a narrow efficacy : toxicity ratio.Pharmacokinetic interactions reported in the literature appear to be more frequent and more important with repaglinide than with nateglinide. Rifampicin (rifampin) reduced repaglinide area under the plasma concentration-time curve (AUC) by 32-85% while it reduced nateglinide AUC by almost 25%. Reported increases in AUCs with coadministration of drugs inhibiting CYP isoenzymes never exceeded 80% for repaglinide (except with ciclosporin and with gemfibrozil) and 50% for nateglinide. Ciclosporin more than doubled repaglinide AUC (+144%), a finding that should raise caution when using these two drugs in combination. The most impressive pharmacokinetic interaction was reported with combined administration of gemfibrozil (a strong CYP2C8 inhibitor) and repaglinide (8-fold increase in repaglinide AUC). Although no studies have been performed in patients with type 2 diabetes, the latter combination should be avoided in clinical practice. [less ▲]

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See detailDrug-Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus.
Scheen, André ULg

in Clinical pharmacokinetics (2014)

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel ... [more ▼]

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (C max) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment. [less ▲]

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See detailDrug-eluting stents: a study of international practice.
Austin, David; Oldroyd, Keith G.; Holmes, David R. Jr et al

in American heart journal (2009), 158(4), 576-84

OBJECTIVE: We aimed to analyze trends in drug-eluting stents (DES) use in four international health care and regulatory settings. BACKGROUND: Accounts suggest a differential approach to DES ... [more ▼]

OBJECTIVE: We aimed to analyze trends in drug-eluting stents (DES) use in four international health care and regulatory settings. BACKGROUND: Accounts suggest a differential approach to DES internationally and recent reductions in use following reports of late stent thrombosis. Current studies of clinical practice are limited in their scope. METHODS: Data were pooled from angioplasty registries in Alberta (Canada), Belgium, Mayo Clinic (Rochester, MN), and Scotland (UK) that have routinely recorded consecutive patients treated since 2003. Trend analysis was performed to examine variations in DES use over time and by clinical subgroup. RESULTS: A total of 178,504 lesions treated between January 2003 and September 2007 were included. In the Mayo Clinic Registry, rapid adoption to a peak of 91% DES use for all lesions by late 2004 was observed. In contrast, Alberta and Scotland showed delayed adoption with lower peak DES use, respectively, 56% and 58% of lesions by early 2006. Adoption of DES in Belgium was more gradual and peak use of 35% lower than other registries. Reductions in DES use were seen in all data sets during 2006, although this varied in absolute and relative terms and by clinical subgroup. CONCLUSION: Adoption and use of DES showed wide variation in four countries. The determinants of use are complex, and it is likely that nonclinical factors predominate. Recent reductions in use may be as a consequence of publicity and concerns regarding late stent thrombosis. The optimum application of DES in clinical practice is unclear and is reflected in the degree of international variation demonstrated. [less ▲]

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See detailDrug-eluting stents: meta-analysis in diabetic patients.
Scheen, André ULg; Warzee, Fabian ULg; Legrand, Victor ULg

in European heart journal (2004), 25(23), 2167-82168-9

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See detailDrug-induced changes in cortical inhibition in medication overuse headache.
Curra, Antonio; Coppola, Gianluca; Gorini, Manuela et al

in Cephalalgia : An International Journal of Headache (2011), 31(12), 1282-90

BACKGROUND: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy ... [more ▼]

BACKGROUND: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. SUBJECTS AND METHODS: We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. RESULTS: In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 +/- 14.2 vs. 108.1 +/- 30.1 ms), but similar to that reported in migraineurs (59.9 +/- 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 +/- 46.4 and 103.8 +/- 47.2 ms). CONCLUSIONS: Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission. [less ▲]

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See detailDrug-induced destructive cholangitis and total ductopenia in a young dog.
gabriel, Alexandra; Heimann, M.; van den ingh, T. et al

in Proceedings of the 13th Annual Congress of the ECVIM-CA (2003)

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See detailDrug-induced thyroid dysfunction
Geenen, Vincent ULg

Conference (2016, April 16)

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See detailDrug-induced toxic epidermal necrolysis and pancytopenia: a puzzling association.
Paquet, Philippe ULg; Jacob, Eric; Pirson, J. et al

in International Journal of Molecular Medicine (2005), 16(1), 29-33

The molecular mechanisms involved in the pathogenesis of toxic epidermal necrolysis (TEN) remain not fully understood. We report a unique case of antibiotic-induced TEN developed in a patient who also ... [more ▼]

The molecular mechanisms involved in the pathogenesis of toxic epidermal necrolysis (TEN) remain not fully understood. We report a unique case of antibiotic-induced TEN developed in a patient who also suffered from prolonged severe methotrexate-induced pancytopenia. The objective of the study was to explore the nature of the cutaneous inflammatory infiltrate and the density in dermal dendrocytes (DD). Immunohistochemistry was used to identify activated T lymphocytes (CD45R0), monocyte-macrophages (Mac 387, CD68), DD (Factor XIIIa), and Langerhans cells (CD1a). The proliferation marker (Ki67) and the antibody to Fas receptor (CD95R) were also used to assess the distribution of the germinative pool of keratinocytes and the FAS-related apoptotic process, respectively. Numerous Factor XIIIa+ DD were present in the papillary dermis with only sparce perivascular CD45RO+ T lymphocytes and scattered CD68+ or Mac 387+ macrophages. Double immunostainings revealed that a minority of Factor XIIIa+ DD co-expressed the CD68 glycoprotein (a marker of phagocytic activity). No cells co-expressed factor XIIIa and Mac 387 immunoreactivities. CD45RO+ T lymphocytes, CD68+ and Mac 387+ macrophages were absent in the epidermis. The expression of CD95R was present although restricted to the basal keratinocytes, while the L1-protein (Mac 387+) was diffusely present in the epidermis. Langerhans cells (CD1a+) were sparce, but normal in distribution. The presence of a great number of Factor XIIIa+ DD without any possible recent recruitment from bone marrow suggests that these cells differentiated from resident cells of the skin. Indeed, there was no co-expression of Factor XIIIa and L1-protein, thus showing the absence of recruitment from monocytes. The simultaneous over-expression of Factor XIIIa and CD68 in some DD indicates some phagocytic activity. In view of the absence of inflammatory cells in the epidermis, keratinocytes appeared responsible for their own destruction through CD95-mediated and/or calcium-dependent apoptotic pathways. This finding entails that TEN treatments should target the keratinocyte metabolism rather than the circulating inflammatory cells which presumably play a limited role, if any, in the epidermal destructive process. [less ▲]

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See detailDrug-induced valvular heart disease.
Cosyns, Bernard; Droogmans, Steven; Rosenhek, Raphael et al

in Heart (British Cardiac Society) (2013), 99(1), 7-12

Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs ... [more ▼]

Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management. [less ▲]

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See detailDrug-polymer electrostatic complexes as new structuring agents for the formation of drug-loaded ordered mesoporous silica
Molina, Emilie; Warnant, Jérôme; Mathonnat, Mélody et al

in Langmuir (2015), 31(47), 12839-12844

Using aminoglycoside antibiotics as drug models, it was shown that electrostatic complexes between hydrophilic drugs and oppositely charged double-hydrophilic block copolymers can form ordered mesophases ... [more ▼]

Using aminoglycoside antibiotics as drug models, it was shown that electrostatic complexes between hydrophilic drugs and oppositely charged double-hydrophilic block copolymers can form ordered mesophases. This phase behaviour was evidenced by using poly(acrylic acid)-block-poly(ethylene oxide) block copolymers in the presence of silica precursors and, this allowed preparing drug-loaded mesoporous silica directly from the drug-polymer complexes. The novel synthetic strategy of the hybrid materials is highly efficient, avoiding waste and multi-step processes; it also ensures optimal drug loading and provides pH-dependence of the drug release from the materials. [less ▲]

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See detailDrugs and "Integrated"Policy. Between Intention and Execution
Lemaître, André ULg; Fincoeur, Bertrand ULg

in Cahiers de la Sécurité (2009)

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See detailDrugs and crime deviant pathways
Born, Michel ULg; Gavray, Claire ULg

in Brochu, S.; Da Agra, C.; Cousineau, M. (Eds.) Deviant trajectories at the turning point between adolescence and adulthood (2002)

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See detailDRUPSSuC : Design and Renovation of Urban Public Spaces for Sustainable Cities, Final report Phase 1
De Herde, André; Vermeir, Gerrit; Godart, Marie-Françoise et al

Report (2009)

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See detailDry galloping on bridge cables: roughness and shape effects on an inclined circular cylinder
Benidir, Adel; Flamand, Olivier; Gaillet, Laurent et al

in Proceedings of the European-African Conference on Wind Engineering 2013 (2013, July 09)

Dry galloping of stays in cable-stayed bridges is a phenomenon that is still of interest to the scientific community. Over the course of the current three-year research project numerous experiments will ... [more ▼]

Dry galloping of stays in cable-stayed bridges is a phenomenon that is still of interest to the scientific community. Over the course of the current three-year research project numerous experiments will be carried out to investigate the effect of turbulence and inclination angle on dry galloping. The novel aspect of this study consists of an in-depth investigation into the effect of non uniformity of the pipe surrounding the stay cables on the dry galloping excitation mechanism. Previous studies reported that dry galloping is caused by the appearance of a negative pressure bubble on one side of the circular cylinder at the critical Reynolds number range, leading to a rapid drop in the drag coefficient and the appearance of a non negligible lift force. This paper presents results from initial experiments in the wind tunnel at CSTB – Nantes, France. [less ▲]

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See detailDry heathlands and sandy open grasslands in a suburban environment in the south of Brussels (Belgium) : Assessment of the conservation status
Taymans, Julien ULg; Mahy, Grégory ULg

Poster (2008, August)

The Brabant sablo-limoneux region is located in the south and near Brussels, in the phytogeographic district of Brabant (Atlantic domain). This region is characterized by a high diversity of local ... [more ▼]

The Brabant sablo-limoneux region is located in the south and near Brussels, in the phytogeographic district of Brabant (Atlantic domain). This region is characterized by a high diversity of local ecological conditions due to the alternance of important tertiary sand outcrops and quaternary silty layers. The agro-sylvo-pastoral activities, which were practiced on these sandy and sand-silty soils for centuries, caused the evolution of the climactic forest into semi-natural habitats such as dry heathland, sandy grassland and grassheath. The evolution of the heathland distribution from 1770 to the present has been studied on the scale of the Dyle hydrographic subbasin (43.000 ha). It is characterized by an important regression of this habitat in the study area (from 1460 ha in 1770 to 72 ha in 2006), mainly due to Pinus sylvestris orchards, and more recently, to urbanisation caused by the proximity of Brussels. A generalized ageing and an environmental closing characterize the evolution of heathland physiognomy since the middle of the 20th century. The phytosociology of heathlands, sandy grasslands and grassheaths has been characterized and 19 groups of vegetation have been differentiated. Among the 393 listed higher plant species, more than 30 are of great conservation interest in the regional context. A hierarchisation of restoration priorities has been established on the scale of the studied hydrographic subbasin and management measures have been proposed. [less ▲]

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