Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value.

Glycated haemoglobin (HbA1c) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA1c value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ). Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA1c. A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA1c value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA1c. Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA1C value in patients in presence of HbJ variant

Neurobiological and pharmacological perspectives of D3 receptors in Parkinson's disease

The discovery of the D3 receptor (D3R) subtypes of dopamine (DA) has generated an understandable increase in interest in the field of neurological diseases, especially Parkinson’s disease (PD). Indeed, although DA replacement therapy with l-DOPA has provided an effective treatment for patients with PD, it is responsible for invalidating abnormal involuntary movements, known as L-DOPA-induced dyskinesia, which constitutes a serious limitation of the use of this therapy. Of particular interest is the finding that chronic l-DOPA treatment can trigger the expression of D1R–D3R heteromeric interactions in the dorsal striatum. The D3R is expressed in various tissues of the central nervous system, including the striatum. Compelling research has focused on striatal D3Rs in the context of PD and motor side effects, including dyskinesia, occurring with DA replacement therapy. Therefore, this review will briefly describe the basal ganglia (BG) and the DA transmission within these brain regions, before going into more detail with regard to the role of D3Rs in PD and their participation in the current treatments. Numerous studies have also highlighted specific interactions between D1Rs and D3Rs that could promote dyskinesia. Finally, this review will also address the possibility that D3Rs located outside of the BG may mediate some of the effects of DA replacement therapy

(+)-Catharanthine and (-)-18-methoxycoronaridine induce antidepressant-like activity in mice by differently recruiting serotonergic and norepinephrinergic neurotransmission

The antidepressant-like activity of (+)-catharanthine and (-)-18-methoxycoronaridine [(-)-18-MC] was studied in male and female mice using forced swim (FST) and tail suspension tests (TST). The underlying molecular mechanism was assessed by electrophysiological, radioligand, and functional experiments. The FST results showed that acute administration (40 mg/kg) of (+)-catharanthine or (-)-18-MC induces similar antidepressant-like activity in male and female mice at 1 h and 24 h, whereas the TST results showed a lower effect for (-)-18-MC at 24 h. Repeated treatment at lower dose (20 mg/kg) augmented the efficacy of both congeners. The FST results showed that (-)-18-MC reduces immobility and increases swimming times without changing climbing behavior, whereas (+)-catharanthine reduces immobility time, increases swimming times more markedly, and increases climbing behavior. To investigate the contribution of the serotonin and norepinephrine transporters in the antidepressant effects of (+)-catharanthine and (-)-18-MC, we conducted in vitro radioligand and functional studies. Results obtained demonstrated that (+)-catharanthine inhibits norepinephrine transporter with higher potency/affinity than that for (-)-18-MC, whereas both congeners inhibit serotonin transporter with similar potency/affinity. Moreover, whereas no congener activated/inhibited/potentiated the function of serotonin receptor 3A or serotonin receptor 3AB, both increased serotonin receptor 3A receptor desensitization. Depletion of serotonin decreased the antidepressant-like activity of both congeners, whereas norepinephrine depletion only decreased (+)-catharanthine’s activity. Our study shows that coronaridine congeners induce antidepressant-like activity in a dose- and time-dependent, and sex-independent, manner. The antidepressant-like property of both compounds involves serotonin transporter inhibition, without directly activating/inhibiting serotonin receptors 3, while (+)-catharanthine also mobilizes norepinephrinergic neurotransmission

Les chymases (rôles et inhibition)

Mises en évidence dans les années 80, les chymases ont tout d'abord été présentées comme des enzymes capables de former l'angiotensine II, par une voie alternative à celle de l'enzyme de conversion. Les modèles expérimentaux ne sont pas tous égaux face à cette production d'angiotensine II. L'étendue de l'implication de ces protéases à sérine au niveau cardiovasculaire va bien au-delà de cette formation. Les chymases pourraient contribuer aux développements physiopathologiques de l'athérosclérose et de l'anévrisme. Leurs répercussions sur l'ensemble de l'organisme sont toujours à l'étude, ainsi que la synthèse d'inhibiteurs, dont certains sont déjà brevetés et s'ajouteront peut-être à l'arsenal thérapeutique de demain.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Approche pratique de l'áérosolthérapie par nébulisation à l'officine

Depuis l'antiquité il a été perçu la pertinence de traiter les voies respiratoires par des aérosols. Aujourd'hui, les aérosols sont produits par des aérosols doseurs dont la technique s'améliore chaque jour et par les générateurs d'aérosols proprement dits dont les spécificités en font des outils thérapeutiques indispensables au traitement de certaines affections respiratoires. Les caractéristiques physiques des aérosols médicamenteux doivent se plier aux caractéristiques anatomiques et physiologiques du système respiratoire. Les différents systèmes de nébulisation ont des modes de fonctionnement particuliers, nécessitant une bonne connaissance du matériel, permettant ainsi de traiter spécifiquement certaines zones des voies respiratoires. Ces systèmes de nébulisation sont utilisables avec des médicaments disposant d'une A.M.M. spécifique ou bien avec certains médicaments reconnus comme étant efficaces. La connaissance du matériel et de son fonctionnement ainsi que la maîtrise des notions de pharmacochimie font du pharmacien un interlocuteur privilégié entre le prescripteur et le patient pour une efficacité thérapeutique optimale.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

La place des bêta-bloquants dans le traitement de l'insuffisance cardiaque

L'insuffisance cardiaque est définie comme l'incapacité du coeur à assurer un débit sanguin suffisant aux besoins métaboliques et fonctionnels des différents organes. Cette pathologie ne cesse de voir le nombre des hospitalisations et des décès augmenter. Afin de maintenir cette maladie à un stade compensé, de nombreux mécanismes compensateurs interfèrent les uns avec les autres. L'un de ces mécanismes est le système sympathique. Cette stimulation noradrénergique, bien qu'elle soit bénéfique à court terme dans l'insuffisance cardiaque, engendre des effets délétères qui peuvent se révéler cardiotoxiques. C'est pourquoi, les bêta-bloquants qui faisaient l'objet d'une contre-indication absolue en raison de leur propriété inotrope négative, ont leur place dans une nouvelle stratégie thérapeutique, afin de réduire les effets des catécholamines dans l'insuffisance cardiaque. Plusieurs molécules sont testées dans le monde entier : métoprolol, bisoprolol, bucindolol, carvédilol et nébivolol. Ces études ont amené à de bons résultats car actuellement deux de ces molécules sont déjà commercialisées : le carvédilol sous le nom de KREDEX® et le bisoprolol sous les noms de CARDENSIEL® et CARDIOCOR®. De nombreuses études sont en route et permettront une utilisation plus sûre et efficace de ces bêta-bloquants par le corps médical.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Serotonin/dopamine interaction: Electrophysiological and neurochemical evidence

The interaction between serotonin (5-HT) and dopamine (DA) in the central nervous system (CNS) plays an important role in the adaptive properties of living animals to their environment. These are two modulatory, divergent systems shaping and regulating in a widespread manner the activity of neurobiological networks and their interaction. The concept of one interaction linking these two systems is rather elusive when looking at the mechanisms triggered by these two systems across the CNS. The great variety of their interacting mechanisms is in part due to the diversity of their neuronal origin, the density of their fibers in a given CNS region, the distinct expression of their numerous receptors in the CNS, the heterogeneity of their intracellular signaling pathway that depend on the cellular type expressing their receptors, and the state of activity of neurobiological networks, conditioning the outcome of their mutual influences. Thus, originally conceptualized as inhibition of 5-HT on DA neuron activity and DA neurotransmission, this interaction is nowadays considered as a multifaceted, mutual influence of these two systems in the regulation of CNS functions. These new ways of understanding this interaction are of utmost importance to envision the consequences of their dysfunctions underlined in several CNS diseases. It is also essential to conceive the mechanism of action of psychotropic drugs directly acting on their function including antipsychotic, antidepressant, antiparkinsonian, and drug of abuse together with the development of therapeutic strategies of Alzheimer's diseases, epilepsy, obsessional compulsive disorders. The 5-HT/DA interaction has a long history from the serendipitous discovery of antidepressants and antipsychotics to the future, rationalized treatments of CNS disorders

Crystal Structure of a New Cation-ordered Fluorite-related Phase: Bi2Te2WO10

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