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See detailPharmacodynamics, Efficacy and Safety of Sodium-Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus.
Scheen, André ULg

in Drugs (2015), 75(1), 33-59

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries ... [more ▼]

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Both effects were very consistent across the trials and they represent some advantages for SGLT2 inhibitors when compared with other oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, and prescribing information for each SGLT2 inhibitor should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Caution is also recommended in the elderly population because of a higher risk of renal impairment, orthostatic hypotension and dehydration, even if the absence of hypoglycaemia represents an obvious advantage in this population. The overall effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and will be evaluated in several ongoing prospective placebo-controlled trials with cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy also deserve more attention. SGLT2 inhibitors are generally well-tolerated. The most frequently reported adverse events are female genital mycotic infections, while urinary tract infections are less commonly observed and generally benign. In conclusion, with their unique mechanism of action that is independent of insulin secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic options available for the management of T2DM at any stage in the natural history of the disease. Although SGLT2 inhibitors have already been extensively investigated, further studies should even better delineate the best place of these new glucose-lowering agents in the already rich armamentarium for the management of T2DM. [less ▲]

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See detailMaterial Flow Visualization Friction Stir Welding via Particle Tracing
Dialami, Narges; Chiumenti, Michele; Cervera, Miguel et al

in International Journal of Material Forming (2015), 8

This work deals with the modeling of the material flow in Friction Stir Welding (FSW) processes using particle tracing method. For the computation of particle trajectories, three accurate and ... [more ▼]

This work deals with the modeling of the material flow in Friction Stir Welding (FSW) processes using particle tracing method. For the computation of particle trajectories, three accurate and computationally efficient integration methods are implemented within a FE model for FSW process: the Backward Euler with Sub-stepping (BES), the 4-th order Runge-Kutta (RK4) and the Back and Forth Error Compensation and Correction (BFECC) methods. Firstly, their performance is compared by solving the Zalesak’s disk benchmark. Later, the developed methodology is applied to some FSW problems providing a quantitative 2D and 3D view of the material transport in the process area. The material flow pattern is compared to the experimental evidence. [less ▲]

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See detailL’agentivité engagée chez Charles Taylor. De l’interprétation à l’évaluation de soi
Gauvry, Charlotte ULg

in Boccaccini, Federico; Cormann, Grégory (Eds.) Le soi agent (2015)

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See detailCancer du sein: intérêt du bilan d’extension par imagerie lors du diagnostic initial et du suivi les trois premières années après le diagnostic
SCHROEDER, Hélène ULg; Hanocq, Florence ULg; COLLIGNON, Joëlle ULg et al

in Revue Médicale de Liège (2015), 70(3), 140-147

In our region, repeated tumor staging by radiological procedures aiming to detect relapses and/or metastases from breast cancer is frequently performed. However, these procedures are not recommended by ... [more ▼]

In our region, repeated tumor staging by radiological procedures aiming to detect relapses and/or metastases from breast cancer is frequently performed. However, these procedures are not recommended by current international guidelines. We retrospectively analyzed the charts from 818 patients with a new diagnosis of breast cancer seen at CHU Liege between 2005 and 2009. We assessed the role of staging procedures at initial diagnosis and during follow-up the first 3 years after the diagnosis of breast cancer. Twenty-six patients presented with metastatic disease at diagnosis and 55 patients developed loco-regional relapses or metastases during follow-up. For asymptomatic patients, imaging procedures only detected tumor metastases or relapse without elevated tumor markers in 9 patients at initial diagnosis and 10 patients during follow-up. The diagnosis of an asymptomatic relapse and/or metastases had no positive impact on progression-free or overall survival. The anatomic extension identified patients at high risk for presenting distant metastases already at the time of initial diagnosis and the biological aggressiveness evaluated by Ki-67 was an important prognostic factor for early relapse. In view of these results, we do not recommend staging and searching for metastatic disease in asymptomatic patients presenting early stage breast cancer with low expression of the Ki-67 at the time of initial diagnosis. We also do not recommend repeated staging and searching for metastases by imaging in asymptomatic patients during routine follow-up. Staging should only be performed if a relapse is suspected during follow-up. [less ▲]

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See detailSynthesis and tensioactive properties of PEO-b-polyphosphate copolymers
Vanslambrouck, Stéphanie ULg; Clément, Benoit; Riva, Raphaël ULg et al

in RSC Advances (2015), 5(35), 27330-37337

Poly(ethylene oxide) (PEO)-b-polyphosphate copolymers made of hydrophilic PEO and hydrophobic polyphosphates are amphiphilic copolymers prone to self-assemble in water into nanoparticles. In this work ... [more ▼]

Poly(ethylene oxide) (PEO)-b-polyphosphate copolymers made of hydrophilic PEO and hydrophobic polyphosphates are amphiphilic copolymers prone to self-assemble in water into nanoparticles. In this work, nanoparticles are obtained by the self-assembly of PEO-b-polyphosphate copolymers in water in the absence of any organic co-solvent whatever the length of the pendant alkyl chain (between 4 and 7 carbon atoms) of the polyphosphate block. Remarkably, this solvent-free process remains efficient even for the most hydrophobic polyphosphate blocks. The critical aggregation concentration (CAC) of the block copolymers was determined by pyrene probe fluorescence. Finally, the efficiency of these copolymer surfactants to decrease the air–water interface was measured by air-bubble tensiometry. [less ▲]

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See detailDéveloppements récents de l'assurance construction en droit européen
Kohl, Benoît ULg

in Revue trimestrielle de droit immobilier (2015), 1

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See detailAntidiabétiques oraux dans le traitement du diabète de type 2 : perspectives historique et médico-économique
SCHEEN, André ULg

in Médecine des Maladies Métaboliques (2015), 9(2), 186-197

Oral therapy of type 2 diabetes (T2D) is becoming increasingly complex during the last decade, with first the launch of glitazones, then that of gliptins and finally, very recently, that of gliflozins ... [more ▼]

Oral therapy of type 2 diabetes (T2D) is becoming increasingly complex during the last decade, with first the launch of glitazones, then that of gliptins and finally, very recently, that of gliflozins. However, the two oral glucose-lowering agents developed more than 50 years ago, metformin and sulfonylureas, still remain the leaders in the market. After failure of metformin monotherapy, the choice of antidiabetic medications is difficult and should be made taking into account the benefit-risk balance, with a special attention to cost of therapy and a focus on a patient-centered approach. This strategy is recommended in the recently updated joint ADA-EASD position statement, in January 2015. If the main principles of T2D therapy are universal, particularities should probably be discussed regarding regional situations, and the African continent obviously presents specificities in this respect. [less ▲]

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See detailLa politique belge dans la question allemande (1945-1990) : une politique de sécurité ?
Brüll, Christoph ULg

in Wintgens, Sophie; Grandjean, Geoffrey; Vanhaeren, Stéphanie (Eds.) L'insécurité en question. Définition, enjeux et perspectives (2015)

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See detailEupen-Malmedy
Brüll, Christoph ULg

in Gruner, Wolf; Osterloh, Jörg (Eds.) The Greater German Reich and the Jews. Nazi Persecution Policies in the Annexed Territories 1935-1945 (2015)

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See detailAssessment of contaminant levels and trophic relations at a World Heritage Site by measurements in a characteristic shorebird species
Schwemmer, Philipp; Covaci, Adrian; Das, Krishna ULg et al

in Environmental Research (2015), 136

The River Elbe is responsible for influxes of contaminants into the Wadden Sea World Heritage Site. We investigated levels of polychlorinated biphenyls (PCBs), oxychlordane (OxC), hexachlorobenzene (HCB ... [more ▼]

The River Elbe is responsible for influxes of contaminants into the Wadden Sea World Heritage Site. We investigated levels of polychlorinated biphenyls (PCBs), oxychlordane (OxC), hexachlorobenzene (HCB), hexachlorocyclohexanes (α-, β-, γ-HCHs), dichlorodiphenyltrichloroethane (DDT) and its metabolites, and polybrominated diphenyl ethers (PBDEs) in blood and feathers from Eurasian oystercatchers (Haematopus ostralegus; n=28) at the Elbe and compared it with a non-riverine site about 90 km further north. (1) Mean levels of all contaminants in feathers and serum were significantly higher at the river (ƩPCBs: 27.6 ng/g feather, 37.0 ng/ml serum; ƩDDTs: 5.3 ng/g feather, 4.4 ng/ml serum) compared with the non-riverine site (ƩPCBs: 6.5 ng/g feather, 1.2 ng/ml serum; ƩDDTs: 1.4 ng/g feather, 0.5 ng/ml serum). Mean ƩHCH and HCB levels were <1.8 ng/g in feather and <1.8 ng/ml in serum at both sites. (2) Levels of most detectable compounds in serum and feathers were significantly related, but levels were not consistently higher in either tissue. (3) There was no significant relationship between trophic level in individual oystercatchers (expressed as δ15N) or the degree of terrestrial feeding (expressed as δ13C) and contaminant loads. (4) PBDEs were not detected in significant amounts at either site. The results of this study indicate that the outflow from one of Europe’s largest river systems is associated with significant historical contamination, reflected by the accumulation of contaminants in body tissues in a coastal benthivore predator. [less ▲]

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See detailMaternal transfer of organohalogenated compounds in sharks and stingrays
Weijs, Liesbeth; Briels, Nathalie; Adams, Douglas et al

in Marine Pollution Bulletin (2015)

Elasmobranchs can bioaccumulate considerable amounts of persistent organic pollutants (POPs) and utilize several reproductive strategies thereby influencing maternal transfer of contaminants. This study ... [more ▼]

Elasmobranchs can bioaccumulate considerable amounts of persistent organic pollutants (POPs) and utilize several reproductive strategies thereby influencing maternal transfer of contaminants. This study provides preliminary data on the POP transfer from pregnant females to offspring of three species (Atlantic stingrays, bonnethead, blacktip sharks) with different reproduction modes (aplacental, placental viviparity). Polychlorinated biphenyl (PCB) levels were generally higher than any other POPs. Stingrays and blacktip shark embryos contained the lowest POP concentrations while bonnetheads and the blacktip adult female had the highest concentrations. Results suggest that are more readily transferred from the mother to the embryo compared to what is transferred to ova in stingrays. Statistically significant differences in levels of selected POPs were found between embryos from the left and right uterus within the same litter as well as between female and male embryos within the same litter for bonnetheads, but not for the blacktip sharks. [less ▲]

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See detailBioaccumulation of organohalogenated compounds in sharks and rays from the southeastern USA
Weijs, Liesbeth; Briels, Nathalie; Adams, Douglas et al

in Environmental Research (2015), 137

Organohalogenated compounds are widespread in the marine environment and can be a serious threat to organisms in all levels of aquatic food webs, including elasmobranch species. Information about the ... [more ▼]

Organohalogenated compounds are widespread in the marine environment and can be a serious threat to organisms in all levels of aquatic food webs, including elasmobranch species. Information about the concentrations of POPs (persistent organic pollutants) and of MeO-PBDEs (methoxylated polybrominated diphenyl ethers) in elasmobranchs is scarce and potential toxic effects are poorly understood. The aims of the present study were therefore to investigate the occurrence of multiple POP classes (PCBs, PBDEs, DDXs, HCB, CHLs) and of MeO-PBDEs in various elasmobranch species from different trophic levels in estuarine and marine waters of the southeastern United States. Overall, levels and patterns of PCBs, PBDEs, DDXs, HCB, CHLs and of MeO-PBDEs varied according to the species, maturity stage, gender and habitat type. The lowest levels of POPs were found in Atlantic stingrays and the highest levels were found in bull sharks. As both species are respectively near the bottom and at top of the trophic web, with juvenile bull sharks frequently feeding on Atlantic stingrays, these findings further suggest a bioaccumulation and biomagnification process with trophic position. MeO-PBDEs were not detected in Atlantic stingrays, but were found in all shark species. HCB was not found in Atlantic stingrays, bonnetheads or lemon sharks, but was detected in the majority of bull sharks examined. Comparison with previous studies suggests that Atlantic stingrays may be experiencing toxic effects of PCBs and DDXs on their immune system. However, the effect of these compounds on the health of shark species remains unclear. [less ▲]

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See detailEdmond de la Coste (1846-1847)
Brüll, Christoph ULg

in Raxhon, Philippe (Ed.) Les Gouverneurs de la Province de Liège. Histoire d'une fonction, mémoire d'une action (2015)

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See detailÀ propos de la régulation des établissements scolaires : analyse de deux dispositifs endogènes comme solution au problème de l'exclusion
Dethier, Baptiste ULg

in Beaumont, Claire; Galand, Benoît; Lucia, Sonia (Eds.) Les violences en milieu scolaire. Définir, prévenir, agir (2015)

Cette contribution présente les résultats de deux études de cas menées dans deux établissements d’enseignement secondaire situés en Belgique francophone. Ces deux écoles ont chacune mis en place un ... [more ▼]

Cette contribution présente les résultats de deux études de cas menées dans deux établissements d’enseignement secondaire situés en Belgique francophone. Ces deux écoles ont chacune mis en place un dispositif d’accrochage scolaire endogène dans le but de lutter plus efficacement contre le décrochage et la violence scolaires et d’offrir une solution au problème de l’exclusion provisoire ou définitive. Ces innovations locales proposent, de manière partielle ou totale, d’accueillir des élèves « en difficulté » et de leur fournir un accompagnement à la fois éducatif et pédagogique, tout en soulageant les enseignants et les autres élèves. La présence de ces jeunes au sein de dispositifs endogènes se veut provisoire et a donc comme objectif leur réintégration en classe, dans « les meilleures conditions possible ». Ce texte décrit des solutions concrètes visant à lutter contre des problèmes concrets tels que le décrochage, la violence ou encore l’absentéisme. À partir d’une démarche qualitative s’inscrivant dans la sociologie de l’action organisée (Friedberg, 1993), nous rendrons compte des acteurs impliqués dans ces projets, de leurs pratiques et des interactions par lesquelles ils les font fonctionner. Cette analyse nous permettra d’étudier, sous ce prisme particulier, la régulation organisationnelle locale. [less ▲]

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See detailL’effet d’un dispositif public belge d’accompagnement sur les parcours professionnels des demandeurs d’emploi
Gérard, Julie ULg

in Meilland, Christèle; Sarfati François, François (Eds.) Accompagner vers l'emploi : quand les dispositifs se mettent en action (2015)

Suite aux récents bouleversements économiques et sociaux touchant les pays de l’Union Européenne, de nombreuses collaborations entre services publics et agences d’emploi privées se sont développées et ... [more ▼]

Suite aux récents bouleversements économiques et sociaux touchant les pays de l’Union Européenne, de nombreuses collaborations entre services publics et agences d’emploi privées se sont développées et complexifiées, suivant une logique de gestion mixte du marché du travail. Cette recherche porte sur l’étude d’un partenariat public-privé entre un service public régional de l’emploi belge et une entreprise marchande. À partir des apports conceptuels et théoriques de la sociologie de l’action publique, nous analyserons la capacité d’un dispositif public à assurer la remise à l’emploi de son public-cible. Pour ce faire, nous étudierons son rôle et ses effets sur les trajectoires professionnelles des demandeurs d’emploi y recourant. [less ▲]

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See detailComplex dynamics of a nonlinear aerospace structure: numerical continuation and normal modes
Renson, Ludovic ULg; Noël, Jean-Philippe ULg; Kerschen, Gaëtan ULg

in Nonlinear Dynamics (2015), 79(2), 1293-1309

This paper investigates the dynamics of a real-life aerospace structure possessing a strongly nonlinear component with multiple mechanical stops. A full-scale finite element model is built for gaining ... [more ▼]

This paper investigates the dynamics of a real-life aerospace structure possessing a strongly nonlinear component with multiple mechanical stops. A full-scale finite element model is built for gaining additional insight into the nonlinear dynamics that was observed experimentally, but also for uncovering additional nonlinear phenomena, such as quasiperiodic regimes of motion. Forced/unforced, damped/undamped numerical simulations are carried out using advanced techniques and theoretical concepts such as numerical continuation and nonlinear normal modes. [less ▲]

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See detailRethinking Vulnerability Analysis and Governance with Emphasis on a Participatory Approach
Rossignol, Nicolas ULg; Delvenne, Pierre ULg; Turcanu, Catrinel

in Risk Analysis : An Official Publication of the Society for Risk Analysis (2015), 35(1), 129-141

This paper draws on vulnerability analysis as it emerged as a complement to classical risk analysis, and it aims at exploring its ability of nurturing risk and vulnerability governance actions. An ... [more ▼]

This paper draws on vulnerability analysis as it emerged as a complement to classical risk analysis, and it aims at exploring its ability of nurturing risk and vulnerability governance actions. An analysis of the literature on vulnerability analysis allows us to formulate a threefold critique: first, vulnerability analysis has been treated separately in the natural and the technological hazards fields. This separation prevents vulnerability to unleash the full range of its potential, as it constraints appraisals into artificial categories and thus already closes down the outcomes of the analysis. Second, vulnerability analysis focused on assessment tools that are mainly quantitative, whereas qualitative appraisal is a key to assessing vulnerability in a comprehensive way and to informing policy-making. Third, a systematic literature review of case studies reporting on participatory approaches to vulnerability analysis allows us to argue that participation has been important to address the above, but it remains too closed down in its approach and would benefit from embracing a more open, encompassing perspective. Therefore, we suggest rethinking vulnerability analysis as one part of a dynamic process between opening-up and closing-down strategies, in order to support a vulnerability governance framework. [less ▲]

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See detailAllogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM-TC)
Guillaume, Thierry; Beguin, Yves ULg; Tabrizi, Reza et al

in European Journal of Haematology (2015), 94

T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell ... [more ▼]

T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T-PLL cases identified in the registry in French Society for stem cell transplantation (SFGM-TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow-up for surviving patients of 33 (range, 6–103) months, 10 patients are still alive in continuous CR. Overall survival and progression-free survival estimates at 3 yr were 36% (95% CI: 17–54%) and 26% (95% CI: 14–45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2–24) months. Overall cumulative incidence of transplant-related mortality was 31% at 3 yr. These results suggest that HSCT may allow long-term survival in patients with T-PLL following induction treatment; however, it is associated with a significant rate of toxicity. [less ▲]

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See detailBilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway
Alhosin, Mahmoud; León-González1, Antonio J.; Dandache et al

in Scientific Reports (2015), 5

Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an ... [more ▼]

Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells isolated from patients but little or no effect in PBMCs. Among the main phenolic compounds present in this bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside showed the highest apoptotic effect on B CLL cells, suggesting that anthocyanins play a main role in the cytotoxic activity. Antho 50-induced apoptosis is associated with activation of caspase 3 and down-regulation of the anti-apoptotic protein UHRF1. Antho 50 induced also rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2 resulting in reduced cell viability. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced reduced cell viability, induction of apoptosis, up-regulation of caspase 3, down-regulation of UHRF1 and Bcl-2, and dephosphorylation of Bad. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of Bad/Bcl-2 pathway. This activity is due, at least in part, to a composition rich on glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells. [less ▲]

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