Angiogenesis

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [Ga]Ga-AP747 and [Ga]Ga-RGD small animal PET/CT. [Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [Ga]Ga-RGD. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [Ga]Ga-AP747 PET signal was more than twice higher than that of [Ga]Ga-RGD on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [Ga]Ga-RGD.France Life Imagin

Partenariat entre patients et formateurs en santé : l'efficacité d'un dispositif pédagogique en formation initiale en Pharmacie

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Partenariat entre patients et formateurs en santé : un dispositif pédagogique en formation initiale en pharmacie

International audienc

L’efficacité d’un dispositif pédagogique universitaire intégrant des patients partenaires. Le cas des internes en pharmacie hospitalière.

International audienc

L’efficacité d’un dispositif pédagogique universitaire intégrant des patients partenaires. Le cas des internes en pharmacie hospitalière.

International audienc

Antinociceptive properties of monoaminergic antidepressants : from depression to neuropathy : Preclinical approach

Il existe une comorbidité entre douleur et dépression. Si les antidépresseurs inhibiteurs de recapture de monoamines représentent le traitement de première intention des troubles dépressifs unipolaires, certains d’entre eux sont également recommandés en première ligne de traitement des douleurs neuropathiques. L’objectif de ce travail a été d’étudier les propriétés analgésiques de ces antidépresseurs dans des modèles animaux co-exprimant des éléments de phénotypes douloureux et dépressifs. Pour cela nous avons développé des tests d’évaluation comportementale de la douleur chez la souris. Ces tests permettent de décrire la sensibilité douloureuse des animaux et d’évaluer les effets pharmacologiques de substances de référence et innovantes.Nous avons ainsi démontré que la fluoxétine, inhibiteur sélectif de la recapture de sérotonine (ISRS), possède des effets antalgiques sur les altérations de sensibilité d’un modèle d’anxiété/dépression chez la souris : le modèle CORT. La caractérisation d’un phénotype douloureux chronique chez ces souris renforce la pertinence de ce modèle neuropsychopharmacologique, puisqu’il exprime une des comorbidités fréquentes des pathologies dépressives. De plus, l’efficacité antalgique de la fluoxétine dans ce modèle plaide en faveur d’une modulation de la composante affective de la douleur par les ISRS.De plus, nous avons caractérisé l’effet antalgique d’une nouvelle classe d’antidépresseurs monoaminergiques, les triples inhibiteurs de recapture des monoamines capables d’augmenter à la fois les concentrations intracérébrales de sérotonine, noradrénaline et dopamine. Pour ce faire, nous avons développé un modèle de douleurs induites par injections répétées d’oxaliplatine chez la souris et comparé l’efficacité de différents traitements sur ces douleurs. Les souris « oxaliplatine » développent une hyperalgie mécanique, ainsi qu’une allodynie et hyperalgie au froid. Ces altérations de la sensibilité douloureuse sont corrigées par l’administration aigüe d’un triple bloqueur (indatraline) en faisant intervenir des mécanismes probablement supra-spinaux. La composante dopaminergique de ces substances apporte un intérêt dans le profil antalgique. Par ailleurs, les souris « oxaliplatine » développent des traits caractéristiques d’un phénotype anxio-dépressif et l’indatraline semble avoir des effets antidépresseurs dans ce modèle, ouvrant la possibilité d’une participation de la DA à la composante affective de la douleur et plus d’effets sur l’influx somatosensoriel. L’ensemble de nos travaux fait ressortir l’importance du développement et de l’utilisation de modèles animaux co-exprimant douleurs et anxiété/dépression afin de mieux définir les mécanismes liant ces pathologies et d’optimiser les critères de développement des futurs antidépresseurs et analgésiques.High comorbidity is described between depression and pain disorders. Monoaminergic reuptake inhibitors represent the first choice of treatment for depression and serotonin and norepinephrin reuptake inhibitors are also recommended for the treatment of neuropathic pain disorders. We aims at evaluating analgesic effects of these drugs in animal models sharing anxio-depressive and painful phenotype. We first developed tests to assess pain sensitivity in mice and analgesic properties of pharmacological compounds. Depressive phenotype was assessed using various behavioural paradigms of anxiety/depression.We thus show that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), provide antinociceptive effects in a mice model of anxiety-depression: the CORT model. Fluoxetine may thus exert its analgesic effect by modulating the affective aspect of pain in addition to a putative influence on sensory mechanisms. Moreover we characterized analgesic effects of a new generation of antidepressant, the triple reuptake inhibitors, which simultaneously potentialisate serotoninergic, noradrenergic and dopaminergic neurotransmission, in a mice model of oxaliplatin-induced neuropathy. Our results support that indatraline provide a better analgesic profile than escitalopram and venlafaxine in pain relief in oxaliplatin-treated mice. Although other investigations are required to quantify the putative involvement of DA in the therapeutic action of indatraline, the benefit can be attributed to this additional component. Indeed, reinforcement of descending control pathways though 5-HT and NE systems has been proposed to participate in the analgesic properties of dual reuptake inhibitors. The fact that indatraline was able to enhance dopaminergic transmission in the Anterior Cingulate Cortex argues in favor of a more potent action upon this inhibitory descending control of pain. Results with indatraline in the depression paradigm cannot rule out the possibility that the antidepressant property of the TRI accounts for its analgesic effect.This work provides a support for the need of animal models sharing anxio/depressive and painful phenotype in order to define mechanism responsible for such co-mobidity and optimize the development of newer antidepressants and pain killers

L’efficacité d’un dispositif pédagogique universitaire intégrant des patients partenaires. Le cas des internes en pharmacie hospitalière.

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Effets antalgiques des antidépresseurs monoaminergiques : de la dépression à la neuropathie : approche préclinique

High comorbidity is described between depression and pain disorders. Monoaminergic reuptake inhibitors represent the first choice of treatment for depression and serotonin and norepinephrin reuptake inhibitors are also recommended for the treatment of neuropathic pain disorders. We aims at evaluating analgesic effects of these drugs in animal models sharing anxio-depressive and painful phenotype. We first developed tests to assess pain sensitivity in mice and analgesic properties of pharmacological compounds. Depressive phenotype was assessed using various behavioural paradigms of anxiety/depression.We thus show that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), provide antinociceptive effects in a mice model of anxiety-depression: the CORT model. Fluoxetine may thus exert its analgesic effect by modulating the affective aspect of pain in addition to a putative influence on sensory mechanisms. Moreover we characterized analgesic effects of a new generation of antidepressant, the triple reuptake inhibitors, which simultaneously potentialisate serotoninergic, noradrenergic and dopaminergic neurotransmission, in a mice model of oxaliplatin-induced neuropathy. Our results support that indatraline provide a better analgesic profile than escitalopram and venlafaxine in pain relief in oxaliplatin-treated mice. Although other investigations are required to quantify the putative involvement of DA in the therapeutic action of indatraline, the benefit can be attributed to this additional component. Indeed, reinforcement of descending control pathways though 5-HT and NE systems has been proposed to participate in the analgesic properties of dual reuptake inhibitors. The fact that indatraline was able to enhance dopaminergic transmission in the Anterior Cingulate Cortex argues in favor of a more potent action upon this inhibitory descending control of pain. Results with indatraline in the depression paradigm cannot rule out the possibility that the antidepressant property of the TRI accounts for its analgesic effect.This work provides a support for the need of animal models sharing anxio/depressive and painful phenotype in order to define mechanism responsible for such co-mobidity and optimize the development of newer antidepressants and pain killers.Il existe une comorbidité entre douleur et dépression. Si les antidépresseurs inhibiteurs de recapture de monoamines représentent le traitement de première intention des troubles dépressifs unipolaires, certains d’entre eux sont également recommandés en première ligne de traitement des douleurs neuropathiques. L’objectif de ce travail a été d’étudier les propriétés analgésiques de ces antidépresseurs dans des modèles animaux co-exprimant des éléments de phénotypes douloureux et dépressifs. Pour cela nous avons développé des tests d’évaluation comportementale de la douleur chez la souris. Ces tests permettent de décrire la sensibilité douloureuse des animaux et d’évaluer les effets pharmacologiques de substances de référence et innovantes.Nous avons ainsi démontré que la fluoxétine, inhibiteur sélectif de la recapture de sérotonine (ISRS), possède des effets antalgiques sur les altérations de sensibilité d’un modèle d’anxiété/dépression chez la souris : le modèle CORT. La caractérisation d’un phénotype douloureux chronique chez ces souris renforce la pertinence de ce modèle neuropsychopharmacologique, puisqu’il exprime une des comorbidités fréquentes des pathologies dépressives. De plus, l’efficacité antalgique de la fluoxétine dans ce modèle plaide en faveur d’une modulation de la composante affective de la douleur par les ISRS.De plus, nous avons caractérisé l’effet antalgique d’une nouvelle classe d’antidépresseurs monoaminergiques, les triples inhibiteurs de recapture des monoamines capables d’augmenter à la fois les concentrations intracérébrales de sérotonine, noradrénaline et dopamine. Pour ce faire, nous avons développé un modèle de douleurs induites par injections répétées d’oxaliplatine chez la souris et comparé l’efficacité de différents traitements sur ces douleurs. Les souris « oxaliplatine » développent une hyperalgie mécanique, ainsi qu’une allodynie et hyperalgie au froid. Ces altérations de la sensibilité douloureuse sont corrigées par l’administration aigüe d’un triple bloqueur (indatraline) en faisant intervenir des mécanismes probablement supra-spinaux. La composante dopaminergique de ces substances apporte un intérêt dans le profil antalgique. Par ailleurs, les souris « oxaliplatine » développent des traits caractéristiques d’un phénotype anxio-dépressif et l’indatraline semble avoir des effets antidépresseurs dans ce modèle, ouvrant la possibilité d’une participation de la DA à la composante affective de la douleur et plus d’effets sur l’influx somatosensoriel. L’ensemble de nos travaux fait ressortir l’importance du développement et de l’utilisation de modèles animaux co-exprimant douleurs et anxiété/dépression afin de mieux définir les mécanismes liant ces pathologies et d’optimiser les critères de développement des futurs antidépresseurs et analgésiques

Implementation of a patient-teaching workshop to improve pharmacy students’ competencies in patient-centered communication: a case report

Abstract Background The pharmacist-patient relationship has evolved over recent decades and the development of clinical pharmacy requires pharmacists to take patient-centered responsibilities. This requires a specific set of skills, such as patient-centered communication. Evaluation of students’ competencies in patient-centered communication is challenging in academic settings and complementary assessment methods may be designed in order to overcome the limits of traditional preceptors’ ratings or objective structured clinical examination (OSCE). There is increasing interest in a more active patient role in healthcare professional education and there are very few reports about patient-led education in pharmacies. Thus, the objective of this work was to implement a patient-teaching workshop and to assess its impact on pharmacy students’ competencies in patient-centered communication. Methods The workshop was developed in collaboration between four patients, a senior clinical pharmacist and a lecturer in education sciences and implemented in the hospital pharmacy residency program. The main course objective was acquiring the three competencies of the Calgary-Cambridge guide to the medical interview: (i) building a relationship, (ii) conducting structured interview and (iii) gathering information. The learning process integrated: working on participants’ perception of pharmacists-patient communication, a first simulated interview, didactic learning and a second simulated interview. After simulated interviews, patients and peer residents assessed learner’s performance with a competency chart and provided individual feedback. Assessment methods included comparisons between the first and second interview scores and an anonymous post-course survey. Results Forty-seven residents and 19 patient teachers attended the session. Competency scores were higher after the second interview in all three competencies as rated by both patients (+ 25%) and peer residents (+ 29%). Residents expressed a high satisfaction and reported learning about conducting interviews and soft skills contributing to the development of a relationship with patients. “The involvement of patients” was expressed as most appreciated in the majority of the evaluation charts (87%) and the residents valued the importance of collaborative and interprofessional learning during the workshop. Three themes emerged: (1) patients’ expertise, (2) reliability and (3) relationship, which underlined that the students estimated the patients were credible sources of information in this pedagogical context. Conclusion This patient-teaching approach improved patient-centered competencies of pharmacy residents and promoted partnership between patients and pharmacy students

Involving patients in a workshop focused on communication skills:a proofofconceptofexperiential trainingforresidents inhospital pharmacy.

International audienceWhat was done?: We developed a workshop involving patients within the training programme of residents in hospital pharmacy. The workshop focused on communication skills needed to improve the quality and effectiveness of a pharmaceutical interview.Why was it done?: The development of clinical pharmacy allows pharmacists to take patient-centered roles and responsibilities. However, patient-centered care requires a specific set of skills and training, such as patient-focused communication and conducting structured interviews. Thus, improvement of pharmacist-patient communication may lead to better clinical outcomes.How was it done?: The workshop was developed jointly by two senior clinical pharmacists and a lecturer in education and communication science. The learning process integrated: working on participants’ perception of pharmacists-patient communication, didactic learning, training activities and evaluation. The assessment of the learning effect was performed by self-, peers-, and patient-scored charts. Patients’ feedback during the training activities and assessments was highlighted as the cornerstone of the learning process.What has been achieved?: First, we built a competency chart on communication skills needed to perform a structured pharmaceutical interview. This tool has been validated by the patients and well accepted by the learners. It was used to assess the learning effect of the workshop, and may serve as a guide for the continuous development of junior practitioners. Secondly, the workshop has actually been implemented, with both the learners and patients expressing a high general acceptance and satisfaction. Finally, preliminary results show a learning effect assessed by both peers and patients.What next?: The involvement of patients needs to be further expanded to the training programmes of undergraduate students, residents and clinical pharmacists. A future action planned is to develop a model with the French Society of Clinical Pharmacy (SFPC) for a national systematic training module: “Improving pharmaceutical interviews’ performance through effective communication”, involving patients