Neurotoxische Enzephalopathie unter Neuroleptika und Lithium

Zusammenfassung: Überlappende neuroleptische Medikationen sind in psychiatrischen Behandlungen gelegentlich unumgänglich. Wir berichten über eine unter schizoaffektiver Störung leidende 60-jährige Frau, welche vorübergehend 3 Neuroleptika und Lithium erhielt. Hierunter entwickelte sie eine neurotoxische Enzephalopathie mit Symptomen eines malignen neuroleptischen Syndroms. Gegenwärtig ist unklar, ob irreversible Hirnschäden zurückbleiben werden. Wir empfehlen engmaschige EEG-Kontrollen zur Früherkennung von Neurotoxizitä

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Aérosols de médicaments

L\u27aérosolthérapie a bénéficié ces dernières années de progrès technologiques considérables au niveau des générateurs d\u27aérosols. Les aérosols doseurs liquides HFA avec ou sans chambre d\u27inhalation, les aérosols doseurs de poudre ont vu leurs indications respectives précisées. Les systèmes de nébulisation ont également progressé avec notamment l\u27apparition des nébuliseurs à membranes. La nébulisation permet de traiter les formes les plus sévères des maladies repiratoires, asthme, BPCO, mucoviscidose, par les bronchodilatateurs, les corticoïdes, les antibiotiques et la rhDNase I. L\u27utilisation de la nébulisation trouve depuis peu des applications pour le traitement de maladies systémiques telles que le diabète ou l\u27hypertension artérielle pulmonaire. Des perspectives apparaissent également pour la chimiothérapie antitumorale et la vaccination par aérosols. Les conditions optimales de prescription, d\u27administration et de suivi de l\u27aérosolthérapie ont été définies

Primer to Voltage Imaging With ANNINE Dyes and Two-Photon Microscopy

ANNINE-6 and ANNINE-6plus are voltage-sensitive dyes that when combined with two-photon microscopy are ideal for recording of neuronal voltages in vivo, in both bulk loaded tissue and the dendrites of single neurons. Here, we describe in detail but for a broad audience the voltage sensing mechanism of fast voltage-sensitive dyes, with a focus on ANNINE dyes, and how voltage imaging can be optimized with one-photon and two-photon excitation. Under optimized imaging conditions the key strengths of ANNINE dyes are their high sensitivity (0.5%/mV), neglectable bleaching and phototoxicity, a linear response to membrane potential, and a temporal resolution which is faster than the optical imaging devices currently used in neurobiology (order of nanoseconds). ANNINE dyes in combination with two-photon microscopy allow depth-resolved voltage imaging in bulk loaded tissue to study average membrane voltage oscillations and sensory responses. Alternatively, if ANNINE-6plus is applied internally, supra and sub threshold voltage changes can be recorded from dendrites of single neurons in awake animals. Interestingly, in our experience ANNINE-6plus labeling is impressively stable in vivo, such that voltage imaging from single Purkinje neuron dendrites can be performed for 2 weeks after a single electroporation of the neuron. Finally, to maximize their potential for neuroscience studies, voltage imaging with ANNINE dyes and two-photon microscopy can be combined with electrophysiological recording, calcium imaging, and/or pharmacology, even in awake animals

The construction of identity through visual intertextuality in a Bohemian early modern travelogue

Cultural historians have long been concerned with visual sources. Their research has centred on ways of reading images and how they can most accurately be interpreted. This article focuses on an alternative aspect of these visual sources: on how images were made and used. It analyses how the identity of a Bohemian Catholic, Bed?ich z Donín, is constructed by his use of images in a travelogue based on his pilgrimage in the early 17th century. Highlighting the process of ‘visual intertextuality’, it claims that the ways in which Donín adopts and adapts visual images reveals his association with various affinity groups. The distinction between ‘actual’ and ‘habitual’ intertextuality is applied to the analysis of this historical source and shows how competing voices are present in the images. This article is an example of how historians can use the methodologies of semioticians to benefit their research

Mitochondrial Morphogenesis, Dendrite Development, and Synapse Formation in Cerebellum Require both Bcl-w and the Glutamate Receptor δ2

Bcl-w belongs to the prosurvival group of the Bcl-2 family, while the glutamate receptor δ2 (Grid2) is an excitatory receptor that is specifically expressed in Purkinje cells, and required for Purkinje cell synapse formation. A recently published result as well as our own findings have shown that Bcl-w can physically interact with an autophagy protein, Beclin1, which in turn has been shown previously to form a protein complex with the intracellular domain of Grid2 and an adaptor protein, nPIST. This suggests that Bcl-w and Grid2 might interact genetically to regulate mitochondria, autophagy, and neuronal function. In this study, we investigated this genetic interaction of Bcl-w and Grid2 through analysis of single and double mutant mice of these two proteins using a combination of histological and behavior tests. It was found that Bcl-w does not control the cell number in mouse brain, but promotes what is likely to be the mitochondrial fission in Purkinje cell dendrites, and is required for synapse formation and motor learning in cerebellum, and that Grid2 has similar phenotypes. Mice carrying the double mutations of these two genes had synergistic effects including extremely long mitochondria in Purkinje cell dendrites, and strongly aberrant Purkinje cell dendrites, spines, and synapses, and severely ataxic behavior. Bcl-w and Grid2 mutations were not found to influence the basal autophagy that is required for Purkinje cell survival, thus resulting in these phenotypes. Our results demonstrate that Bcl-w and Grid2 are two critical proteins acting in distinct pathways to regulate mitochondrial morphogenesis and control Purkinje cell dendrite development and synapse formation. We propose that the mitochondrial fission occurring during neuronal growth might be critically important for dendrite development and synapse formation, and that it can be regulated coordinately by multiple pathways including Bcl-2 and glutamate receptor family members

Ten new insights in climate science 2024

The years 2023 and 2024 were characterized by unprecedented warming across the globe, underscoring the urgency of climate action. Robust science advice for decision makers on subjects as complex as climate change requires deep cross- and interdisciplinary understanding. However, navigating the ever-expanding and diverse peer-reviewed literature on climate change is enormously challenging for individual researchers. We elicited expert input through an online questionnaire (188 respondents from 45 countries) and prioritized 10 key advances in climate-change research with high policy relevance. The insights span a wide range of areas, from changes in methane and aerosol emissions to the factors shaping citizens’ acceptance of climate policies. This synthesis and communications effort forms the basis for a science-policy report distributed to party delegations ahead of the 29th session of the Conference of the Parties (COP29) to inform their positions and arguments on critical issues, including heat-adaptation planning, comprehensive mitigation strategies, and strengthened governance in energy-transition minerals value chains

In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors

Adult human cardiac mesenchymal-like stromal cells (CStC) represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS) in the presence of 5 \ub5M all-trans Retinoic Acid (ATRA), 5 \ub5M Phenyl Butyrate (PB), and 200 \ub5M diethylenetriamine/nitric oxide (DETA/NO), to create a novel epigenetically active cocktail (EpiC). Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and \u3b1-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f) current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors