Transcranial magnetic stimulation in depression--lessons from the multicentre trials

Looking at novelties and advances in medicine in particular in the treatment of major depressive disorder no principally new antidepressant treatment strategy has been established in clinical routine in the last fifty years. However, regarding the considerable issue of treatment resistance in depression, new therapeutic strategies are urgently required. In this context, repetitive transcranial magnetic stimulation above the dorsolateral prefrontal cortex has been proposed as a potential new treatment option for depression; furthermore, in October 2008 a first rTMS-device (NeuroStar TMS Therapy System™) was approved by the FDA for the treatment of treatment resistant major refractory depression in adults. Yet, despite now nearly two decades of research in this field, no final answer concerning its validity for antidepressant treatment in the clinical practice is given. Numerous studies with small sample sizes and heterogeneous designs have been performed in this field yielding to different results. These were subjected to meta-analyses, assessing the antidepressant effect of rTMS, which are briefly summarized in this article. Further, multicentre-trials with larger numbers of patients were performed, which are presented and critically discussed here in more detail. This short review shall thus provide an overview of the current status of knowledge concerning rTMS in depression and it also provides some recommendations for future research in this field

Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation

Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self-regulation and appraisal

New Inhibitors of the Na+/K+-ATPase from Helleborus purpurascens

Aus den Wurzeln der Pflanze Helleborus purpurascens wurde die lipophile Vorstufe eines potenten Hemmstoffes der Na+/K+-ATPase isoliert. Die Vorstufe konnte durch eine Basen/Säure Behandlung reproduzierbar in ihre eigentlich aktive Form überführt werden. Diese wurde als macrocyclic carbon suboxide (MCS) Faktor bezeichnet, welcher eine neue Substanzklasse makrozyklischer, kondensierter 4H-Pyran-4-one darstellt. Für die hypothetische Struktur der MCS-Faktoren mit der allgemeinen Formel (C3O2)n konnten massenspektrometrische Belege der Existenz eines Hexameren und Octameren erbracht werden. Zur weiteren Charakterisierung wurden Synthesestrategien für Modellverbindungen dieser Klasse entwickelt und durchgeführt.From the roots of Helleborus purpurascens a lipophilic inhibitor of the Na+/K+-ATPase was isolated which upon a base/acid treatment was converted in reproducible manner into an even more active form. Based on its putative structure, the inhibitor was named macrocyclic carbon suboxide (MCS) factor which represents a new class of macrocyclic condensed 4H-pyran-4-ones. The hexameric and octameric structure of these compounds of the general formula (C3O2)n are supported by mass-spectrometric analysis. For further characterization of the natural products synthetic strategies for model compounds were developed

Ontologien zur Validierung von Produkten basierend auf dem Contact & Channel - Ansatz (C&C²-Ansatz) = Ontologies for the Validation of Products based on the Contact & Channel Approach (C&C²- Approach)

Im Rahmen der Arbeit wurden Ontologien entwickelt, mit denen kausale Zusammenhänge rechnerverständlich modelliert und auf Sinnhaftigkeit hin überprüft werden können. Basierend auf den vermuteten kausalen Zusammenhängen, werden mittels dieser Ontologien des Weiteren zielgerichtete Experimente entworfen. Somit können in einer frühen Phase der Entwicklung statistisch abgesicherte und nachvollziehbare Entscheidungen basierend auf dem zukünftigen Produktverhalten getroffen werden

ADN and HAN-based energetic fuels – A Minireview on compatibility and chemical stability in aqueous media

This article gives a short review on compatibility and chemical stability of selected aqueous ADN and HAN‐based energetic formulations. A brief introduction will outline Energetic Ionic Liquids (EILs) as a new class of energetic materials with beneficial physical‐chemical properties which make them valuable for application in propulsion technologies. EILs combine the advantages of e. g. low toxicity, showing equal or superior propulsion power compared to the state‐of‐the‐art monopropellant hydrazine. Focus is set on open access ADN and HAN‐based monopropellant formulations that are e. g. realized in the advanced blends LMP‐103S, FLP‐106 or LGP 1845

Hybrid Models for Efficient Control, Optimization, and Monitoring of Thermo-Chemical Processes and Plants

This paper describes a procedure and an IT product that combine numerical models, expert knowledge, and data-based models through artificial intelligence (AI)-based hybrid models to enable the integrated control, optimization, and monitoring of processes and plants. The working principle of the hybrid model is demonstrated by NOx reduction through guided oscillating combustion at the pulverized fuel boiler pilot incineration plant at the Institute for Technical Chemistry, Karlsruhe Institute of Technology. The presented example refers to coal firing, but the approach can be easily applied to any other type of nitrogen-containing solid fuel. The need for a reduction in operation and maintenance costs for biomass-fired plants is huge, especially in the frame of emission reductions and, in the case of Germany, the potential loss of funding as a result of the Renewable Energy Law (Erneuerbare-Energien-Gesetz) for plants older than 20 years. Other social aspects, such as the departure of experienced personnel may be another reason for the increasing demand for data mining and the use of artificial intelligence (AI)

Paliperidone extended-release: does it have a place in antipsychotic therapy?

Paliperidone (9-hydroxy-risperidone), the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER), and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially higher costs as compared with risperidone. However, in terms of pharmacology, the available evidence cautiously suggests a place for PER in modern antipsychotic therapy

Formation of Columnar Liquid Crystals on the Basis of Unconventional Triazine-Based Dendrimers by the C3-Symmetric Approach

[[abstract]]Two series of unconventional triazine-based dendrimers with C2 symmetry and C3 symmetry were prepared. The newly prepared C3-symmetrical dendrimers were characterized by 1H and 13C NMR spectroscopy, mass spectrometry, and elemental analysis. Differential scanning calorimetry, polarizing microscopy, and powder XRD showed that the C3-symmetrical dendrimers display columnar liquid-crystalline phases during thermal treatment, but the C2-symmetrical dendrimers were not observed to behave correspondingly. The molecular conformations of C3- and C2-symmetrical dendrimers were obtained by computer simulation with the MM2 model of the CaChe program in the gas phase. The simulation results reasonably explain the different mesogenicities of C3- and C2-symmetric dendrimers. This new strategy should be applicable to other types of unconventional dendrimers with rigid frameworks for displaying columnar liquid-crystalline behavior.[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]紙本[[countrycodes]]DE