Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile during alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the “drinking in the dark” (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50 % in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4, however, were altered in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm are restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption.     

In search of the Holy Grail of Rodent control: Step-by-step implementation of safe and sustainable-by-design principles on the example of rodenticides

The field of chemical rodent control has seen no major developments in the last decades, even though anticoagulant rodenticides (AR), the mainly used substances to manage mice and rats, are known environmental pollutants and candidates for substitution under the European Biocidal Products Regulation 528/2012. Moreover, recent political developments in Europe and the USA demand more safety and sustainability in the management of chemicals, reinforcing the need for environmentally friendly substances. In this concept study, we present a step-by-step approach to improve the environmental properties of rodenticides. Repurposing of existing pharmaceuticals, the use of enantiomerically pure rodenticides, or the improvement of the formulation by microencapsulation can help to alleviate environmental problems caused by AR in the short term. Modification of the chemical structures or the development of prodrugs as medium-term strategies can further improve environmental properties of existing compounds. Ultimately, the development of new substances from scratch enables the utilisation of so far ignored modes of actions and the application of modern safe and sustainable-by-design principles to improve target specificity and reduce the negative impact on non-target organisms and the environment. Overall, our concept study illustrates the great potential for improvement in the field of chemical rodent control when applying available techniques of green and sustainable chemistry to known or potential rodenticides. Most promising in the medium term is microencapsulation that would allow for the use of acutely acting substances as it could circumvent bait shyness. On a longer timescale the de novo design of new rodenticides, which is the only method that can combine a high target specificity with good environmental properties, is the most promising approach.     

Aktuelle Entwicklungen und Einsatzgebiete von Schulterorthesen

The use of shoulder braces has become more important recently. Although the effectiveness and actual need of different shoulder braces have not yet undergone an evidence-based evaluation, empirical data shows differentiated use of shoulder braces not only in postoperative care but also for non-surgical treatment. For this, not only biological factors (lengths of immobilisation and tissue healing), but also biomechanical factors (pathology-adapted immobilisation) need to be considered.Apart from simple slings, physicians can choose between two different types of braces: soft shoulder braces and rigid shoulder braces. Future studies should evaluate commercially available shoulder braces on their functionality and comfort as well as for potential problems related to different pathologies of the shoulder joint and its clinical outcome.     

Functional parcellation of the inferior frontal and midcingulate cortices in a flanker‐stop‐change paradigm

Conflict monitoring and motor inhibition are engaged in the performance of complex tasks. The midcingulate cortex (MCC) has been suggested to detect conflicts, whereas the right inferior frontal cortex (IFC) seems to be of relevance for the inhibition process. The current experiment investigates the neural underpinnings of their interplay via a modified flanker paradigm. Conflict was manipulated by the congruency of flanking stimuli relative to a target (congruent vs. incongruent) and motor inhibition by a within‐trial response change of the initiated response (keep response vs. stop‐change). We used event‐related functional magnetic resonance imaging, decomposition with high model order ICA, and single trial analysis to derive a functional parcellation of the whole‐brain data. Results demonstrate the segmentation of the MCC into anterior and posterior subregions, and of the IFC into the pars opercularis, pars triangularis, and pars orbitalis. The pars opercularis and pars triangularis of the right IFC constituted the foundation of inhibition‐related networks. With high conflict on incongruent trials, activity in the posterior MCC network, as well as in one right IFC network was observed. Stop‐change trials modulated both the MCC as well as networks covering extended parts of the IFC. Whereas conflict processing and inhibition most often are studied separately, this study provides a synopsis of functionally coupled brain regions acting in concert to enable an optimal performance in situations involving interference and inhibition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.