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1.
ALTEX ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33086382

RESUMO

Evaluating stress in laboratory animals is a key principle in animal welfare. Measuring corticosterone is a common method to assess stress in laboratory mice. There are, however, numerous methods to measure glucocorticoids with differences in sample matrix (e.g. plasma, urine) and quantification techniques (e.g. EIA, RIA). Here, the authors present a mapping review and have produced a searchable database, giving a complete overview of all studies measuring endogenous corticosterone in mice up to February 2018. For each study, information was recorded regarding mouse strain and sex; corticosterone sample matrix and quantification technique; and whether the studies covered the research themes animal welfare, neuroscience, stress, inflammation, or pain (the themes of specific interest in our consortium). Using all database entries for the year 2012, an exploratory meta-regression was performed to determine the effect of predictors on basal corticosterone concentrations. Seventy-five studies were included using the predictors of sex, time-since-lights-on, sample matrix, quantification technique, age of the mice, and type of control. Sex, time-since-lights-on, and type of control significantly affected basal corticosterone concentrations. The resulting database can be used, inter alia, for preventing unnecessary duplication of experiments, identifying knowledge gaps, and standardizing or heterogenizing methodologies. Therefore, these results will help plan more efficient and valid experiments in the future and can answer new questions in silico using meta-analyses.

2.
Sci Rep ; 10(1): 17295, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057103

RESUMO

Buprenorphine is a frequently used analgetic agent in veterinary medicine. A major drawback, however, is the short duration of action requiring several daily administrations. We therefore designed a poly-lactic-co-glycolic acid (PLGA) based microparticulate drug formulation for sustained parenteral drug release. Particles were designed to allow for a fast onset of action and a duration of the analgesic effect of at least two days in laboratory mice. Microparticles were produced using a solvent evaporation technique. Release rate was dependent on polymer type and particle size. Spherical particles used for subsequent animal studies had a mean size of 50 µm and contained 4.5% of buprenorphine. Drug release was characterized by an initial burst release of 30% followed by complete release over seven days. In vivo pharmacokinetic experiments in female C57BL/6 J mice confirmed prolonged exposure in plasma and brain tissue and correlated with the pharmacological effect in the hot plate assay or after minor abdominal surgery. No adverse side effects with respect to food and water intake, body weight, local tolerability, or nesting behavior were observed. Our formulation is an attractive alternative to established immediate release formulations. A use for prolonged pain management in laboratory animals is proposed.

3.
Lab Anim ; 54(1): 26-32, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31657274

RESUMO

Severity assessment for experiments conducted with laboratory animals is still based mainly on subjective evaluations; evidence-based methods are scarce. Objective measures, amongst which determination of the concentrations of stress hormones, can be used to aid severity assessment. Short-term increases in glucocorticoid concentrations generally reflect healthy responses to stressors, but prolonged increases may indicate impaired welfare. As mice are the most commonly used laboratory animal species, we performed a systematic mapping review of corticosterone measurements in Mus musculus, to provide a full overview of specimen types (e.g. blood, urine, hair, saliva, and milk) and analysis techniques. In this publication, we share our protocol and search strategy, and our rationale for performing this systematic analysis to advance severity assessment. So far, we have screened 13,520 references, and included 5337 on primary studies with measurements of endogenous corticosterone in M. musculus. Data extraction is currently in progress. When finished, this mapping review will be a valuable resource for scientists interested in corticosterone measurements to aid severity assessment. We plan to present the data in a publication and a searchable database, which will allow for even easier retrieval of the relevant literature. These resources will aid implementation of objective measures into severity assessment.


Assuntos
Corticosterona/metabolismo , Manejo de Espécimes/métodos , Animais , Corticosterona/sangue , Corticosterona/urina , Camundongos , Leite/química , Saliva/química , Revisões Sistemáticas como Assunto
4.
Lab Anim ; 54(1): 73-82, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696771

RESUMO

Evidence-based severity assessment is essential as a basis for ethical evaluation in animal experimentation to ensure animal welfare, legal compliance and scientific quality. To fulfil these tasks scientists, animal care and veterinary personnel need assessment tools that provide species-relevant measurements of the animals' physical and affective state. In a three-centre study inter-laboratory robustness of body weight monitoring, mouse grimace scale (MGS) and burrowing test were evaluated. The parameters were assessed in naïve and tramadol treated female C57BL/6J mice. During tramadol treatment a body weight loss followed by an increase, when treatment was terminated, was observed in all laboratories. Tramadol treatment did not affect the MGS or burrowing performance. Results were qualitatively comparable between the laboratories, but quantitatively significantly different (inter-laboratory analysis). Burrowing behaviour seems to be highly sensitive to inter-laboratory differences in testing protocol. All locations obtained comparable information regarding the qualitative effect of tramadol treatment in C57BL/6J mice, however, datasets differed as a result of differences in test and housing conditions. In conclusion, our study confirms that results of behavioural testing can be affected by many factors and may differ between laboratories. Nevertheless, the evaluated parameters appeared relatively robust even when conditions were not harmonized extensively and present useful tools for severity assessment. However, analgesia-related side effects on parameters have to be considered carefully.


Assuntos
Analgésicos Opioides/uso terapêutico , Peso Corporal , Atividade Motora , Medição da Dor/métodos , Índice de Gravidade de Doença , Tramadol/uso terapêutico , Bem-Estar do Animal , Animais , Expressão Facial , Feminino , Camundongos Endogâmicos C57BL
5.
Lab Anim ; 54(1): 92-98, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31660777

RESUMO

The Mouse Grimace Scale (MGS) is an established method for estimating pain in mice during animal studies. Recently, an improved and standardized MGS set-up and an algorithm for automated and blinded output of images for MGS evaluation were introduced. The present study evaluated the application of this standardized set-up and the robustness of the associated algorithm at four facilities in different locations and as part of varied experimental projects. Experiments using the MGS performed at four facilities (F1-F4) were included in the study; 200 pictures per facility (100 pictures each rated as positive and negative by the algorithm) were evaluated by three raters for image quality and reliability of the algorithm. In three of the four facilities, sufficient image quality and consistency were demonstrated. Intraclass correlation coefficient, calculated to demonstrate the correlation among raters at the three facilities (F1-F3), showed excellent correlation. The specificity and sensitivity of the results obtained by different raters and the algorithm were analysed using Fisher's exact test (p < 0.05). The analysis indicated a sensitivity of 77% and a specificity of 64%. The results of our study showed that the algorithm demonstrated robust performance at facilities in different locations in accordance with the strict application of our MGS setup.


Assuntos
Medição da Dor/métodos , Dor/fisiopatologia , Índice de Gravidade de Doença , Estresse Psicológico/fisiopatologia , Animais , Expressão Facial , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dor/induzido quimicamente , Estresse Psicológico/etiologia , Gravação em Vídeo
6.
Sci Rep ; 9(1): 10749, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31341225

RESUMO

Adequate analgesia is essential whenever pain might occur in animal experiments. Unfortunately, the selection of suitable analgesics for mice in bone-linked models is limited. Here, we evaluated two analgesics - Tramadol [0.1 mg/ml (Tlow) vs. 1 mg/ml (Thigh)] and Buprenorphine (Bup; 0.009 mg/ml) - after a pre-surgical injection of Buprenorphine, in a mouse-osteotomy model. The aim of this study was to verify the efficacy of these opioids in alleviating pain-related behaviors, to provide evidence for adequate dosages and to examine potential side effects. High concentrations of Tramadol affected water intake, drinking frequency, food intake and body weight negatively in the first 2-3 days post-osteotomy, while home cage activity was comparable between all groups. General wellbeing parameters were strongly influenced by anesthesia and analgesics. Model-specific pain parameters did not indicate more effective pain relief at high concentrations of Tramadol. In addition, ex vivo high-resolution micro computed tomography (µCT) analysis and histology analyzing bone healing outcomes showed no differences between analgesic groups with respect to newly formed mineralized bone, cartilage and vessels. Our results show that high concentrations of Tramadol do not improve pain relief compared to low dosage Tramadol and Buprenorphine, but rather negatively affect animal wellbeing.


Assuntos
Analgésicos/administração & dosagem , Buprenorfina/administração & dosagem , Osteotomia , Dor Pós-Operatória/tratamento farmacológico , Tramadol/administração & dosagem , Administração Oral , Animais , Modelos Animais de Doenças , Água Potável , Feminino , Fêmur/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cuidados Pós-Operatórios/métodos
7.
Acta Biomater ; 86: 171-184, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616076

RESUMO

Although several biomaterials for bone regeneration have been developed in the last decades, clinical application of bone morphogenetic protein 2 is clinically only approved when applied on an absorbable bovine collagen I scaffold (ACS) (Helistat; ACS-H). In research, another ACS, namely Lyostypt (ACS-L) is frequently used as a scaffold in bone-linked studies. Nevertheless, until today, the influence of ACS alone on bone healing remains unknown. Unexpectedly, in vitro studies using ASC-H revealed a suppression of osteogenic differentiation and a significant reduction of cell vitality when compared to ASC-L. In mice, we observed a significant delay in bone healing when applying ACS-L in the fracture gap during femoral osteotomy. The results of our study show for the first time a negative influence of both ACS-H and ACS-L on bone formation demonstrating a substantial need for more sophisticated delivery systems for local stimulation of bone healing in both clinical application and research. STATEMENT OF SIGNIFICANCE: Our study provides evidence-based justification to promote the development and approval of more suitable and sophisticated delivery systems in bone healing research. Additionally, we stimulate researchers of the field to consider that the application of those scaffolds as a delivery system for new substances represents a delayed healing approach rather than a normal bone healing which could greatly impact the outcome of those studies and play a pivotal role in the translation to the clinics. Moreover, we provide impulses on underlying mechanism involving the roles of small-leucine rich proteoglycans (SLRP) for further detailed investigations.


Assuntos
Colágeno Tipo I/farmacologia , Consolidação da Fratura/efeitos dos fármacos , Osteotomia , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Calo Ósseo/patologia , Calcificação Fisiológica/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/ultraestrutura , Modelos Animais de Doenças , Endotélio/efeitos dos fármacos , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Fator de Necrose Tumoral alfa/metabolismo , Microtomografia por Raio-X
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