Polyimide-ald-polyimide layers as hermetic encapsulant for implants

Several requirements exist for medical devices for long term implantation. Firstly, the foreign body reaction and/or inflammation occurring upon implantation should remain mild and short in time. Moreover, the device needs to be biocompatible during the total implantation duration, hence not causing reactions which decrease the patient’s health. Finally, the device needs to work properly and safe during the total period of implantation, not suffering from corrosion or chemical degradation. To meet these requirements, diffusion of body fluids into the package should be avoided as well as diffusion of toxic device materials into the body, hence a hermetic packaging method is an absolute necessity. Here, a flexible hermetic packaging is presented using alternating polyimide and atomic layer deposited (ALD) metal oxides. Good adhesion between the inorganic ALD layers and the polyimide is required to avoid the creation of lateral diffusion pads. To obtain this, surface modifications of both polyimide and ALD layers are optimized, as presented in this paper. The hermeticity is evaluated in terms of water vapor transmission rate measurements of the film stack

Orbital bleeding in rats while under diethylether anaesthesia does not influence telemetrically determined heart rate, body temperature, locomotor and eating activity when compared with anaesthesia alone

The question addressed was whether orbital bleeding in rats, while under diethylether anaesthesia, affects their locomotor activity, body core temperature, heart rate rhythm and eating pattern. Roman High Avoidance (RHA) and Roman Low Avoidance (RLA) rats were used to enhance generalization of the results. Orbital bleeding when the rats were under diethylether anaesthesia was compared with diethylether anaesthesia alone. To take into account any effects of handling, the rats were also subjected to sham anaesthesia. The RHA rats urinated more during anaesthesia, needed more time to recover from the anaesthesia and showed a greater endocrine stress response to diethylether anaesthesia when compared with the RLA rats. During anaesthesia, the RHA rats showed a greater fall of body temperature and bradycardia than did the RLA rats. Diethylether anaesthesia reduced locomotor activity in the RHA rats, but had no effect in the RLA rats. In neither RHA nor RLA rats did anaesthesia plus orbital puncture, versus anaesthesia alone, influence body temperature, heart rate rhythm, locomotor and eating activity. The lack of effect of orbital puncture occurred both in the short term (within 2 h) and long term (within 48 hours) and thus this study indicates that orbital puncture had, at least with respect to variables measured in the present study, no effect superimposed on that of diethylether anaesthesia

Animal models for arthritis: innovative tools for prevention and treatment

The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature and to propose new strategies for preventive, early and curative treatments. Research on animal models has generated new knowledge on RA pathophysiology and aetiology and has provided highly successful paradigms for innovative drug development. Recent focus has shifted towards the discovery of novel biomarkers, with emphasis on presymptomatic and emerging stages of human RA, and towards addressing the pathophysiological mechanisms and subsequent efficacy of interventions that underlie different disease variants. Shifts in the current paradigms underlying RA pathogenesis have also led to increased demand for new (including humanised) animal models. There is therefore an urgent need to integrate the knowledge on human and animal models with the ultimate goal of creating a comprehensive 'pathogenesis map' that will guide alignment of existing and new animal models to the subset of disease they mimic. This requires full and standardised characterisation of all models at the genotypic, phenotypic and biomarker level, exploiting recent technological developments in '-omics' profiling and computational biology as well as state of the art bioimaging. Efficient integration and dissemination of information and resources as well as outreach to the public will be necessary to manage the plethora of data accumulated and to increase community awareness and support for innovative animal model research in rheumatology

A questionnaire-based inventory of the orbital puncture method in the Netherlands

To contribute to the assessment of the degree of discomfort in rodents as caused by orbital puncture, we made an inventory in the Netherlands on the basis of an inquiry. Orbital puncture is being performed in laboratory rodents more than 45000 times a year. Usually, ether is used as anaesthetic. In about two-third of the institutes where orbital puncture is being performed, complications are noted. In I to 5 % of the animals punctured blindness can occur. In more than half of the instituteswhere orbital puncture is being performed there are objections to this technique. Which are essentially of an emotional/ethical nature

Standardisation of Environmental Enrichment for Laboratory Mice and Rats: Utilisation, Practicality and Variation in Experimental Results

Rats and mice are the most commonly used species as laboratory animal models of diseases in biomedical  research. Environmental factors such as cage size, number of cage mates and cage structure such as environmental  enrichment can affect the physiology and behavioural development of laboratory animals and  their well-being throughout their lives. Therefore compromising the animals’ well-being due to inadequate  environmental conditions would diminish the value of the research models. In order to improve laboratory  animals’ well-being and promote the quality of animal based biomedical research, it is fundamentally  important that the environment of the animals meets the animals’ species typical behavioural needs. Standardisation  of environmental enrichment for laboratory rats and mice therefore should provide possibilities  for the animals to engage in at least the essential behavioural needs such as social contact, nest building,  exploring and foraging. There is a wide variety of environmental enrichment items commercially available  for laboratory mice and rats. However, how these items are used by the animals, their practicality in the  laboratory and whether these enrichments might lead to increased variation in experimental results have  not been widely assessed. In this study, we implemented two standardised enrichment items (shelters, nesting  materials) for rats and mice at different animal units. We instructed the animal care staff in monitoring  the use of enrichment items by the animals by means of a daily score sheet system. The animal staff ’s  viewpoint on practicality of the standardised enrichment program was assessed with a monthly score sheet  survey. Also we assessed whether the enriched environment affected breeding results and contributed to an  increase in variation of experimental data from several participating current studies. Our results show that  the animals readily used the provided enrichment items. A slight increase in workload for the animal staff  was reported. However, the overall judgement was mainly reported as good. Breeding results and variation  in experimental data did not reveal differences as compared to data from previous housing and/or non enriched  housing conditions. Overall, the results indicate that standard environmental enrichment that is species  appropriate may enhance the animal’s well-being without undesirable side effects on the experimental  outcome and daily working routine of the animal care staff.

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

FROM PRECONCEIVED IDEAS ON HYSTERIA TO FUNCTIONAL NEUROLOGICAL DISORDER

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