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Animal models are pivotal for studies of pathogenesis and treatment of disorders of the central nervous system which in its complexity cannot yet be modeled in vitro or using computer simulations. The choice of a specific model to test novel therapeutic strategies for a human disease should be based on validity of the model for the approach: does the model reflect symptoms, pathogenesis and treatment response present in human patients? In the movement disorder dystonia, prior to the availability of genetically engineered mice, spontaneous mutants were chosen based on expression of dystonic features, including abnormal muscle contraction, movements and postures. Recent discovery of a number of genes and gene products involved in dystonia initiated research on pathogenesis of the disorder, and the creation of novel models based on gene mutations. Here we present a review of current models of dystonia, with a focus on genetic rodent models, which will likely be first choice in the future either for pathophysiological or for preclinical drug testing or both. In order to help selection of a model depending on expression of a specific feature of dystonia, this review is organized by symptoms and current knowledge of pathogenesis of dystonia. We conclude that albeit there is increasing need for research on pathogenesis of the disease and development of improved models, current models do replicate features of dystonia and are useful tools to develop urgently demanded treatment for this debilitating disorder. [ABSTRACT FROM AUTHOR]

Abstract: Primary dystonia is a common movement disorder with an unknown pathophysiology, but basal ganglia dysfunctions seem to play a critical role. Previous studies in the dt sz mutant hamster, an animal model of primary paroxysmal dystonia, demonstrated a deficit of striatal γ-amino-butyric acid (GABA) containing interneurons, which normalized at the age of the spontaneous remission of the symptoms. Whereas the reduction of striatal parvalbumin-reactive interneurons is thought to be critically involved in the pathogenesis of dystonia in the hamster mutant, the impact of a reduced density of nitric oxide synthase (NOS) reactive interneurons within the striatum is still unclear. Beside GABA, these interneurons contain somatostatin, neuropeptide Y, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and neuronal NOS, an enzyme which produces NO after the activation of the interneurons. In order to clarify if the reduced density of NOS-reactive interneurons contributes by an altered striatal production of nitric oxide (NO) to the occurrence of dystonic attacks in the hamster mutant, we performed microinjections of the NOS inhibitors 7-nitroindazole (7-NI) and Nω-propyl-l-arginine (NPLA) and of the precursor of NO, l-arginine, into the striata of dt sz hamsters. Neither 7-NI (0.1 and 0.4μg per hemisphere) and NPLA (2.5, 5 and 7.5μg per hemisphere) nor l-arginine (9 and 18μg per hemisphere) exerted any effects on the severity of dystonic movements in the dt sz mutant. Therefore, a critical involvement of striatal changes of NO in the pathophysiology of dystonic attacks in the dt sz hamster cannot be confirmed by the results of these pharmacological examinations. In view of the ontogenetic reduction of the other types of GABAergic interneurons, the deficit of NOS-reactive interneurons is possibly due to the same underlying unknown mechanism, but is less important for the pathophysiology of primary paroxysmal dystonia in the dt sz hamster mutant. [Copyright &y& Elsevier]

Abstract: Objective: Assessment of the use of a computerized information-tool in the context of a shared decision-making process with chronic pain patients. Methods: In the scope of a prospective and randomized study on shared decision-making with Fibromyalgia patients, a total of 75 patients had access to computer-based information about their illness. Fibromyalgia is a condition of chronic wide-spread pain, belonging to rheumatism, which mainly affects mature female patients. The majority of the patients in our study are female (93%) with an average age of 50 years. The computer-based information-tool provided the patients with detailed information about pathogenesis, typical symptoms, treatment options and prognosis. Six evaluative questions were posed to the participants concerning the assessment of the information presented, the handling of the programme, the need for an introduction to the programme, the quality of the layout and the assessment of the length of time spent in front of the computer and the assessment of the usefulness of such a tool in general practitioners’ offices. Furthermore, psychological self-assessment questionnaires were filled out by the participants. Results: The patients highly appreciate the possibility of using computer-based information-tools and endorse the implementation of such tools in general practitioners’ offices. Conclusion: Computerized information leads to a better understanding of the illness and the treatment options on the part of the patient. Practical implications: For further practical use it is crucial to provide an introduction to the handling of a computer to unskilled patients. [Copyright &y& Elsevier]

• Antimicrobial treatment failure is an important threat. • In-vitro resistance is not the only reason for therapeutic failure. • Better understanding of possible reasons can help to avoid treatment failures. • Facts that can result in ineffective antibacterial treatment are summarized. • The communication on therapeutic failure can help to improve the antimicrobial use. The choice of the most suitable antimicrobial agent for the treatment of an animal suffering from a bacterial infection is a complex issue. The results of bacteriological diagnostics and the in-vitro antimicrobial susceptibility testing (AST) provide guidance of potentially suitable antimicrobials. However, harmonized AST methods, veterinary-specific interpretive criteria and quality control ranges, which are essential to conduct AST in-vitro and to evaluate the corresponding results lege artis , are not available for all antimicrobial compounds, bacterial pathogens, animal species and sites of infection of veterinary relevance. Moreover, the clinical benefit of an antimicrobial agent (defined as its in vivo efficacy) is not exclusively dependent on the in-vitro susceptibility of the target pathogen. Apart from the right choice of an antibacterial drug with suitable pharmacokinetic properties and an appropriate pharmaceutical formulation, the success of treatment depends substantially on its adequate use. Even if this is ensured and in-vitro susceptibility confirmed, an insufficient improvement of clinical signs might be caused by biofilm-forming bacteria, persisters, or specific physicochemical conditions at the site of infection, such as pH value, oxygen partial pressure and perfusion rate. This review summarizes relevant aspects that have an impact on the predictive value of in-vitro AST and points out factors, potentially leading to an ineffective outcome of antibacterial treatment in veterinary practice. Knowing the reasons of inadequate beneficial effects can help to understand possible discrepancies between in-vitro susceptibility and in vivo efficacy and aid in undertaking strategies for an avoidance of treatment failures. [ABSTRACT FROM AUTHOR]

Highlights: [•] Retigabine, a KV7.2–5 opener, shows antidyskinetic effects in a rat model of LID. [•] We examined if this effect was mainly mediated by KV7.2/3 channels. [•] Indeed, the KV7.2/3 preferring channel opener ICA 27243 attenuated LID. [•] We suggest an antidyskinetic action mainly mediated by striatal KV7.2/3 channels [ABSTRACT FROM AUTHOR]