Alteration of T cell cytokine production in PLPp-139-151-induced EAE in SJL mice by an immunostimulatory CpG Oligonucleotide

Experimental autoimmune encephalomyelitis (EAE) is - in certain aspects - regarded as an animal model of the human CNS autoimmune disease multiple sclerosis (MS). While in EAE CNS-autoantigen-specific immunity is induced in a defined way, the initial processes leading to CNS autoimmunity in humans are so far unknown. Despite essential restrictions, which exist regarding the interpretation of EAE data towards MS, EAE might be a useful model to study certain basic aspects of CNS autoimmunity. Studies in MS have demonstrated that established autoimmune pathology can be critically influenced by environmental factors, in particular viral and bacterial infections. To investigate this interaction, EAE as an instrument to study CNS autoimmunity under defined conditions appears to be a suitable experimental tool. For this reason, we here investigated the influence of the Toll-like-receptor (TLR) ligand CpG oligonucleotide (CpG) on already established CNS autoimmunity in murine proteolipid protein (PLP)-induced EAE in SJL mice. CpG were found to co-stimulate PLPp-specific IFN-γ production in the peripheral immune system and in the CNS. However, CpG induced Interleukin (IL)-17 production in the inflamed CNS both alone and in combination with additional PLPp stimulation. These findings might indicate a mechanism by which systemic infections and the microbial stimuli associated with them may influence already existing CNS autoimmune pathology

Two Distinct Clinical Courses of Human Cowpox, Germany, 2015

Here we present two cases of human infection with cowpox virus with distinct clinical courses. A series of clinical photographs documents lesion progression over time. In the first case—an unvaccinated young veterinary assistant—a pustule was treated locally with cortisone. The lesion turned into a large ulcer accompanied by severe lymphadenitis. Based on her close contact to a sick stray cat, infection with cowpox virus was assumed and confirmed by virus isolation, PCR, and serology. The clinical course took up to eleven months until healing of the wound was complete. Transmission of cowpox virus from the cat was likely because a skin swab was PCR-positive and the cat had a high titer of anti-orthopoxvirus antibodies. In contrast, a rather mild clinical course of cowpox was confirmed in a 49-year-old male farmer vaccinated against smallpox. Only a small eschar developed, and wound closure was complete after 6 weeks

The Combination of Interferon-Beta and HMG-CoA Reductase Inhibition in Multiple Sclerosis: Enthusiasm Lost too Soon?

Recent studies support the notion that statins, widely prescribed cholesterol-lowering agents, may target key elements in the immunological cascade leading to inflammation and tissue damage in the pathogenesis of multiple sclerosis (MS). Compelling experimental and observational clinical studies highlighted the possibility that statins may also exert immunomodulatory synergy with approved MS drugs, resulting in several randomized clinical trials testing statins in combination with interferon-beta (IFN-?). Some data, however, suggest that this particular combination may not be clinically beneficial, and might actually have a negative effect on the disease course in some patients with MS. In this regard, a small North American trial indicated that atorvastatin administered in combination with IFN-? may increase disease activity in relapsing-remitting MS. Although other trials did not confirm this finding, the enthusiasm for studies with statins dwindled. This review aims to provide a comprehensive overview of the completed clinical trials and reports of the interim analyses evaluating the combination of IFN-? and statins in MS. Moreover, we try to address the evident question whether usage of this combination routinely requires caution, since the number of IFN-?-treated MS patients receiving statins for lowering of cholesterol is expected to grow

Radical Deuteration with D₂O: Catalysis and Mechanistic Insights

Selective incorporation of deuterium atoms into molecules is of high interest for labeling purposes and for optimizing properties of drug candidates. A mild and environmentally benign method for the deuteration of alkyl iodides via radical pathway using D₂O as source of deuterium has been developed. The reaction is initiated and mediated by triethylborane in the presence of dodecanethiol as a catalyst. This method is compatible with a wide range of functional groups and provides the monodeuterated products in good yields and with a high level of deuterium incorporation. It opens promising opportunities for the development of enantioselective radical reactions. Moreover, a revision of the mechanism of the deoxygenation reaction of xanthates using R₃B and water (Wood deoxygenation) is presented

Collaborative table-top VR display for neurosurgical planning

We present a prototype of a system in development for pre-operative planning. The proposed NeuroTable uses a combination of traditional rendering and novel visualization techniques rendered to facilitate real-time collaboration between neurosurgeons during intervention planning. A set of multimodal 2D and 3D renderings convey the relation between the region of interest and the surrounding anatomical structures. A haptic device is used for interaction with the NeuroTable to facilitate immersive control over the 3D cursor and navigation modes for the neurosurgeons during their discourse of planning. A pilot experimental study was conducted to assess the performance of users in targeting points within the preoperative 3D scan. Then, two clinicians participated in the evaluation of the table in discussing and planning a case. Results indicate that the NeuroTable facilitated the discourse and we discuss the results of the speed and accuracy for the specification of entry and target points