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1.
J Vet Med Educ ; : e20200094, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33929287

RESUMO

Online-based processing of case reports is often used and well accepted in veterinary medical education. However, lecturers usually develop cases from their own point of view, without input from students. In order to give students the chance to create online cases for students, an elective course, "Creative Workshop Case Creation", was held three times between 2017 and 2019 at the Faculty of Veterinary Medicine, Freie Universität Berlin. During this course, students created cases based on animal welfare and epizootics issues through a problem-based blended learning approach. In this approach, students worked on an assigned veterinary public health problem and actively solved it in small groups in class and then used the issue as the basis to create cases for their fellow students. The cases were implemented in interdisciplinary lectures, which are mandatory for every student in semesters six to eight. After taking these classes, fellow students evaluated one of these cases, specifically, on animal welfare and another one on epizootics. Evaluations showed these cases were received well. Moreover, we received excellent feedback from students participating in the elective course and working with a proactive and motivated group of six students throughout the course was a very productive experience. The course made it possible to create cases that are more accurately tailored to the needs of students. The students' good ideas and preparatory work also saved time in the preparation of cases for lecturers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33579043

RESUMO

Nearly 59,000 human deaths worldwide are attributable to rabies annually, of which more than a third occur in Africa. In recent years, progress has been made in both action and collaboration including implementation of surveillance and prevention measures. In this review we assess the scale of surveillance, preventive, and control efforts of canine-transmitted human rabies in African countries. We reviewed literature published from 2014 to 2018, retrieved from electronic databases including MEDLINE, Global Index Medicus, BIOSIS, Science Citation Index, and EMBASE. WHO reports, national disease control program reports, and conference proceedings were also reviewed. The database search was conducted using keywords including rabies, control, and prevention. In forty countries (40/54), some level of rabies control and prevention strategy was available while in fourteen (14/54) countries, no specific national control and prevention strategy for human rabies could be retrieved. Thirty-four (34/54) countries utilized the Stepwise Approach towards Rabies Elimination (SARE) tool to monitor the national rabies control efforts-five of these countries were at the lowest tier (0/5) of the SARE scoring system while no country had achieved the highest score (5/5). High burden countries need to step up the implementation of context specific national rabies control, prevention, and monitoring strategies. As a zoonosis, rabies control and elimination require coordination between human and veterinarian health sectors under the "One Health" umbrella and with national master plans on the prevention and control of neglected tropical diseases ending in 2020, the time to act is now.


Assuntos
Doenças do Cão , Vacinas Antirrábicas , Raiva , África/epidemiologia , Animais , Erradicação de Doenças , Doenças do Cão/epidemiologia , Doenças do Cão/prevenção & controle , Cães , Humanos , Políticas , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterinária
3.
J Bone Miner Res ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534144

RESUMO

After trauma, the formed fracture hematoma within the fracture gap contains all the important components (immune/stem cells, mediators) to initiate bone regeneration immediately. Thus, it is of great importance but also the most susceptible to negative influences. To study the interaction between bone and immune cells within the fracture gap, up-to-date in vitro systems should be capable of recapitulating cellular and humoral interactions and the physicochemical microenvironment (eg, hypoxia). Here, we first developed and characterized scaffold-free bone-like constructs (SFBCs), which were produced from bone marrow-derived mesenchymal stromal cells (MSCs) using a macroscale mesenchymal condensation approach. SFBCs revealed permeating mineralization characterized by increased bone volume (µCT, histology) and expression of osteogenic markers (RUNX2, SPP1, RANKL). Fracture hematoma (FH) models, consisting of human peripheral blood (immune cells) mixed with MSCs, were co-cultivated with SFBCs under hypoxic conditions. As a result, FH models revealed an increased expression of osteogenic (RUNX2, SPP1), angiogenic (MMP2, VEGF), HIF-related (LDHA, PGK1), and inflammatory (IL6, IL8) markers after 12 and 48 hours co-cultivation. Osteogenic and angiogenic gene expression of the FH indicate the osteoinductive potential and, thus, the biological functionality of the SFBCs. IL-6, IL-8, GM-CSF, and MIP-1ß were detectable within the supernatant after 24 and 48 hours of co-cultivation. To confirm the responsiveness of our model to modifying substances (eg, therapeutics), we used deferoxamine (DFO), which is well known to induce a cellular hypoxic adaptation response. Indeed, DFO particularly increased hypoxia-adaptive, osteogenic, and angiogenic processes within the FH models but had little effect on the SFBCs, indicating different response dynamics within the co-cultivation system. Therefore, based on our data, we have successfully modeled processes within the initial fracture healing phase in vitro and concluded that the cross-talk between bone and immune cells in the initial fracture healing phase is of particular importance for preclinical studies. © 2021 American Society for Bone and Mineral Research (ASBMR).

4.
Mol Imaging ; 19: 1536012120961875, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216687

RESUMO

BACKGROUND: Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1ß (IL-1ß) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1ß-therapy on AAA-formation in a mouse-model. METHODS: Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1ß-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg). RESULTS: Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R2 = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R2 = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1ß-expression. CONCLUSIONS: Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1ß-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.

5.
Animals (Basel) ; 10(11)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33171996

RESUMO

The most common feather sampling method for feather corticosterone measurement is by plucking the feathers from the bird's skin. This procedure performed on living, restrained birds is qualified as an animal experiment according to German/European legislation, which has to be applied for from the competent authorities. The Directive 2010/63/EU requires the full implementation of the 3-R Principle of Russel and Burch in animal experiments, which means not only to replace the use of animals, but also to reduce the number of animals used and to refine procedures whenever possible. In response to this issue, the aim of this study was to validate an alternative, less invasive sampling method by cutting feathers close to the skin in comparison to the gold standard of plucking them. For this proof-of-principle study, a conventional poultry husbandry with trial groups of geese (Anser anser domesticus) and ducks (Anas sterilis) was selected. All birds were kept under the same living conditions to standardize the influencing factors regarding husbandry, and thus, their stress levels. Feather samples were collected between the shoulders from 46 geese and 51 ducks, both by cutting as well as by plucking, directly after slaughter for meat production. Feather corticosterone levels were measured with Enzyme-Linked Immunosorbent Assay (ELISA). Results were compared using Bland-Altman plots and concordance correlation coefficients (CCC). It could be seen that concordance between corticosterone levels in cut and plucked feathers was rather poor: 0.38 for Anser, and 0.57 for Anas. However, comparing the mean corticosterone values in pg/mm of each species with their respective standard deviations, the differences between the methods were negligible. As the results showed that the differences between the individuals were markedly greater than the differences between the methods, the determination of corticosterone levels in cut feathers is valid compared to using plucked feathers. The validation tests of ELISA showed only acceptable repeatability and reliability. Hence, the results should be verified in further studies. In conclusion, it is recommended for future research to use cut instead of plucked feathers for corticosterone measurement.

7.
Animals (Basel) ; 10(9)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937881

RESUMO

To maintain and foster the welfare of laboratory mice, tools that reliably measure the current state of the animals are applied in clinical assessment. One of these is the Mouse Grimace Scale (MGS), a coding system for facial expression analysis. Since there are concerns about the objectivity of the MGS, we further investigated its reliability. Four observers (two experienced and two inexperienced in use of the MGS) scored 188 images of 33 female and 31 male C57BL/6JRj mice. Images were generated prior to, 150 min, and two days after ketamine/xylazine anesthesia. The intraclass correlations coefficient (ICC = 0.851) indicated good agreement on total MGS scores between all observers when all three time points were included in the analysis. However, interrater reliability was higher in the early post-anesthetic period (ICC = 0.799) than at baseline (ICC = 0.556) and on day 2 after anesthesia (ICC = 0.329). The best agreement was achieved for orbital tightening, and the poorest agreement for nose and cheek bulge, depending on the observers' experience levels. In general, experienced observers produced scores of higher consistency when compared to inexperienced. Against this background, we critically discuss factors that potentially influence the reliability of MGS scoring.

8.
Sci Rep ; 10(1): 11165, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636413

RESUMO

Laboratory male mice are often housed individually due to aggressive behavior or experimental requirements, though social isolation can cause welfare issues. As a strategy to refine housing of male mice, we introduce the separated pair housing system. A perforated transparent wall divides the cage into two compartments and allows olfactory, acoustic, and visual communication between the two mice but prevents fighting and injuries. Long-term effects of separated pair housing on well-being and distress of adult male C57BL/6JRj mice were investigated and compared with both single- and group-housed mice. Behavioral analysis after eight weeks in three different housing systems revealed no differences in burrowing performance, social interaction, anxiety, and stress hormone concentrations. However, pair-housed mice built more complex nests compared to single-housed mice and the nest position suggested that pair-housed mice preferred the close proximity to their cage mates. Moreover, pair-housed mice showed less locomotor activity compared to group- and single-housed mice. Body weight was higher in group-housed mice. All in all, no unambiguous long-term beneficial effects of pair housing on the well-being were found. However, the findings emphasized that effects of the housing systems on behavioral, physical, and biochemical parameters must be considered in the design of animal experimental studies.

9.
ALTEX ; 37(4): 561-578, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32521037

RESUMO

The aim of the study was to establish an in vitro fracture hematoma (FH) model that mimics the in vivo situation of the human fracture gap in order to assess drug efficacy and effectiveness for the treatment of fracture healing disorders. Human peripheral blood and mesenchymal stromal cells (MSCs) were coagulated to produce in vitro FH models, which were incubated in osteogenic medium under normoxia/hypoxia and analyzed for cell composition, gene expression and cytokine/chemokine secretion. To evaluate the model, we studied the impact of dexamethasone (impairing fracture healing) and deferoxamine (promoting fracture healing). Under hypoxic conditions, MSCs represented the predominant cell population, while the frequencies of leukocyte populations decreased. Marker gene expression of osteogenesis, angiogenesis, inflammation, migration and hypoxic adaptation increased significantly over time and compared to normoxia, while cytokine/chemokine secretion remained unchanged. Dexamethasone favored the frequency of immune cells compared to MSCs, suppressed osteogenic and pro-angiogenic gene expression, and enhanced the secretion of inflammatory cytokines. Conversely, deferoxamine favored the frequency of MSCs over that of immune cells and enhanced the expression of the osteogenic marker RUNX2 and markers of hypoxic adaptation. In summary, we demonstrate that hypoxia is an important factor for modeling the initial phase of fracture healing in vitro and that both fracture-healing disrupting and promoting substances can influence the in vitro model comparable to the in vivo situation. Therefore, we conclude that our model is able to mimic in part the human FH and could reduce the number of animal experiments in early preclinical studies.

10.
PeerJ ; 8: e8629, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32435527

RESUMO

As has been hypothesized more than 20 years ago, data derived from Electroencephalography (EEG) measurements can be used to distinguish between behavioral states associated with animal welfare. In our current study we found a high degree of correlation between the modulation index of phase related amplitude changes in the EEG of horses (n = 6 measurements with three different horses, mare and gelding) and their facial expression, measured by the use of the horse grimace scale. Furthermore, the pattern of phase amplitude coupling (PAC) was significantly different between a rest condition and a stress condition in horses. This pilot study paves the way for a possible use of EEG derived PAC as an objective tool for the assessment of animal welfare. Beyond that, the method might be useful to assess welfare aspects in the clinical setting for human patients, as for example in the neonatal intensive care unit.

12.
Animals (Basel) ; 10(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244837

RESUMO

Deflighting zoo birds is a practice that receives increasing criticism due to its presumed incompatibility with animal welfare. To our knowledge, this is the first approach to address this problem in a scientific way. To do this, we compared feather corticosterone (CORTf) from Greater Flamingos (Phoenicopterus roseus, n = 151) of different flight status (i.e., pinioned, feather clipped, airworthy) from twelve different zoological institutions. To complement the hormone measurements, behavioral observations (scan samplings) were conducted prior to feather sampling within the presumed time frame of feather growth. We hypothesized that CORTf of the deflighted flamingos would differ from CORTf of their airworthy conspecifics. No significant difference in CORTf was found between the three groups, and our hypothesis was rejected. However, the impact of the institution itself (i.e., the housing conditions) proved to be the most dominant variable (variance between the institutions = 53.82%). Due to high variability, the behavioral observations were evaluated descriptively but did not give rise to doubt the findings in CORTf. Therefore, we assume that the method of flight restraint of Greater Flamingos does not have a measurable effect on CORTf. We consider this model for evaluating animal welfare of zoo birds a useful tool and provide ideas for further adjustments for consecutive studies.

13.
PLoS One ; 15(4): e0228059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294094

RESUMO

Assessing the well-being of an animal is hindered by the limitations of efficient communication between humans and animals. Instead of direct communication, a variety of parameters are employed to evaluate the well-being of an animal. Especially in the field of biomedical research, scientifically sound tools to assess pain, suffering, and distress for experimental animals are highly demanded due to ethical and legal reasons. For mice, the most commonly used laboratory animals, a valuable tool is the Mouse Grimace Scale (MGS), a coding system for facial expressions of pain in mice. We aim to develop a fully automated system for the surveillance of post-surgical and post-anesthetic effects in mice. Our work introduces a semi-automated pipeline as a first step towards this goal. A new data set of images of black-furred laboratory mice that were moving freely is used and provided. Images were obtained after anesthesia (with isoflurane or ketamine/xylazine combination) and surgery (castration). We deploy two pre-trained state of the art deep convolutional neural network (CNN) architectures (ResNet50 and InceptionV3) and compare to a third CNN architecture without pre-training. Depending on the particular treatment, we achieve an accuracy of up to 99% for the recognition of the absence or presence of post-surgical and/or post-anesthetic effects on the facial expression.


Assuntos
Bem-Estar do Animal , Animais de Laboratório/fisiologia , Aprendizado Profundo , Ciência dos Animais de Laboratório/métodos , Dor Pós-Operatória/diagnóstico , Anestésicos/administração & dosagem , Animais , Comportamento Animal/fisiologia , Castração/efeitos adversos , Conjuntos de Dados como Assunto , Expressão Facial , Feminino , Masculino , Camundongos/fisiologia , Dor Pós-Operatória/etiologia
14.
Front Vet Sci ; 7: 81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32154276

RESUMO

Keel bone fractures and deviations belong to the most severe animal welfare problems in laying hens and are influenced by several factors such as husbandry system and genetic background. It is likely that egg production also influences keel bone health due to the high demand of calcium for the eggshell, which is, in part, taken from the skeleton. The high estrogen plasma concentration, which is linked to the high laying performance, may also affect the keel bone as sexual steroids have been shown to influence bone health. The aim of this study was to investigate the relationship between egg production, genetically determined high laying performance, estradiol-17ß concentration, and keel bone characteristics. Two hundred hens of two layer lines differing in laying performance (WLA: high performing; G11: low performing) were divided into four treatment groups: Group S received an implant containing a GnRH agonist that suppressed egg production, group E received an implant containing the sexual steroid estradiol-17ß, group SE received both implants, and group C were kept as control hens. Between the 12th and the 62nd weeks of age, the keel bone of all hens was radiographed and estradiol-17ß plasma concentration was assessed at regular intervals. Non-egg laying hens showed a lower risk of keel bone fracture and a higher radiographic density compared to egg laying hens. Exogenous estradiol-17ß was associated with a moderately higher risk of fracture within egg laying but with a lower risk of fracture and a higher radiographic density within non-egg laying hens. The high performing layer line WLA showed a significantly higher fracture risk but also a higher radiographic density compared to the low performing layer line G11. In contrast, neither the risk nor the severity of deviations were unambiguously influenced by egg production or layer line. We assume that within a layer line, there is a strong association between egg production and keel bone fractures, and, possibly, bone mineral density, but not between egg production and deviations. Moreover, our results confirm that genetic background influences fracture prevalence and indicate that the selection for high laying performance may negatively influence keel bone health.

15.
Sci Rep ; 9(1): 13827, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554825

RESUMO

Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE-/-) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R2 = 0.83, p < 0.05; Perls' Prussian-blue-stain: y = 834.1 + 0.67, R2 = 0.88, p < 0.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p < 0.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p < 0.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The in-vivo detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.


Assuntos
Óxido Ferroso-Férrico/administração & dosagem , Gadolínio/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Imagem por Ressonância Magnética/métodos , Placa Aterosclerótica/tratamento farmacológico , Pravastatina/administração & dosagem , Animais , Meios de Contraste , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Elastina/metabolismo , Estudos de Viabilidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Camundongos , Camundongos Knockout para ApoE , Óxido Nítrico/metabolismo , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/metabolismo , Pravastatina/uso terapêutico , Sensibilidade e Especificidade
16.
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
17.
Contrast Media Mol Imaging ; 2019: 5461809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275084

RESUMO

Background: Magnetic resonance angiography (MRA) represents a clinical reference standard for the in vivo assessment of the vasculature. In this study, the potential of non-contrast-enhanced and contrast-enhanced angiography of the head/neck vasculature in mice on a clinical MR imaging system was tested. Methods: All in vivo magnetic resonance imaging was performed with a 3T clinical system (Siemens). Non-contrast-enhanced (time-of-flight, TOF) and contrast-enhanced angiography (gadofosveset-trisodium, GdT) were performed in C57BL/6J mouse strain. Lumen-to-muscle ratios (LMRs) and area measurements were assessed. Histology was performed as reference standard of all relevant vascular structures. Results: A close correlation between TOF (R 2 = 0.79; p < 0.05) and contrast-enhanced (GdT) angiography (R 2 = 0.92; p < 0.05) with histological area measurements was found. LMRs were comparable between both sequences. Regarding interobserver reproducibility, contrast-enhanced (GdT) angiography yielded a smaller 95% confidence interval and a closer interreader correlation compared to non-contrast-enhanced (TOF) measurements (-0.73-0.89; R 2 = 0.81 vs. -0.55-0.56; R 2 = 0.94). Conclusion: This study demonstrates that non-contrast-enhanced and contrast-enhanced angiographies of the head/neck vasculature of small animals can reliably performed on a clinical 3T MR scanner. Contrast-enhanced angiography enables the visualization of vascular structures with higher intravascular contrast and higher reproducibility.


Assuntos
Meios de Contraste/farmacologia , Gadolínio/farmacologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Compostos Organometálicos/farmacologia , Animais , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Humanos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Camundongos
18.
PLoS One ; 14(4): e0214276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30947253

RESUMO

Fractures in horses-whether simple fractures with just one clean break, or incomplete greenstick with stress fractures, or complications such as shattered bones can all be either minimal or even catastrophic. Thus, improvement in fracture healing is a hallmark in equine orthopedics. The fracture healing process implements a complex sequence of events including the initial inflammatory phase removing damaged tissue, re-establishment of vessels and mesenchymal stromal cells, a soft and hard callus phase closing the fracture gap as well as the remodeling phase shaping the bone to a scar-free tissue. Detailed knowledge on processes in equine fracture healing in general and on the initial phase in particular is apparently very limited. Therefore, we generated equine in vitro fracture hematoma models (FH models) to study time-dependent changes in cell composition and RNA-expression for the most prominent cells in the FH model (immune cells, mesenchymal stromal cells) under conditions most closely adapted to the in vivo situation (hypoxia) by using flow cytometry and qPCR. In order to analyze the impact of mesenchymal stromal cells in greater detail, we also incubated blood clots without the addition of mesenchymal stromal cells under the same conditions as a control. We observed a superior survival capacity of mesenchymal stromal cells over immune cells within our FH model maintained under hypoxia. Furthermore, we demonstrate an upregulation of relevant angiogenic, osteogenic and hypoxia-induced markers within 48 h, a time well-known to be crucial for proper fracture healing.


Assuntos
Consolidação da Fratura , Fraturas Ósseas/patologia , Fraturas Ósseas/terapia , Hematoma/terapia , Hipóxia/patologia , Células-Tronco Mesenquimais/citologia , Modelos Biológicos , Animais , Biomarcadores/metabolismo , Biópsia , Sobrevivência Celular/efeitos dos fármacos , Consolidação da Fratura/efeitos dos fármacos , Hematoma/patologia , Cavalos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Oxigênio/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos
19.
Circ Cardiovasc Imaging ; 12(3): e008707, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30871334

RESUMO

BACKGROUND: Molecular magnetic resonance imaging is a promising modality for the characterization of abdominal aortic aneurysms (AAAs). The combination of different molecular imaging biomarkers may improve the assessment of the risk of rupture. This study investigates the feasibility of imaging inflammatory activity and extracellular matrix degradation by concurrent dual-probe molecular magnetic resonance imaging in an AAA mouse model. METHODS: Osmotic minipumps with a continuous infusion of Ang II (angiotensin II; 1000 ng/[kg·min]) to induce AAAs were implanted in apolipoprotein-deficient mice (N=58). Animals were assigned to 2 groups. In group 1 (longitudinal group, n=13), imaging was performed once after 1 week with a clinical dose of a macrophage-specific iron oxide-based probe (ferumoxytol, 4 mgFe/kg, surrogate marker for inflammatory activity) and an elastin-specific gadolinium-based probe (0.2 mmol/kg, surrogate marker for extracellular matrix degradation). Animals were then monitored with death as end point. In group 2 (week-by-week-group), imaging with both probes was performed after 1, 2, 3, and 4 weeks (n=9 per group). Both probes were evaluated in 1 magnetic resonance session. RESULTS: The combined assessment of inflammatory activity and extracellular matrix degradation was the strongest predictor of AAA rupture (sensitivity 100%; specificity 89%; area under the curve, 0.99). Information from each single probe alone resulted in lower predictive accuracy. In vivo measurements for the elastin- and iron oxide-probe were in good agreement with ex vivo histopathology (Prussian blue-stain: R2=0.96, P<0.001; Elastica van Giesson stain: R2=0.79, P<0.001). Contrast-to-noise ratio measurements for the iron oxide and elastin-probe were in good agreement with inductively coupled mass spectroscopy ( R2=0.88, R2=0.75, P<0.001) and laser ablation coupled to inductively coupled plasma-mass spectrometry. CONCLUSIONS: This study demonstrates the potential of the concurrent assessment of inflammatory activity and extracellular matrix degradation by dual-probe molecular magnetic resonance imaging in an AAA mouse model. Based on the combined information from both molecular probes, the rupture of AAAs could reliably be predicted.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Elastina/metabolismo , Matriz Extracelular/metabolismo , Óxido Ferroso-Férrico/administração & dosagem , Gadolínio DTPA/administração & dosagem , Mediadores da Inflamação/metabolismo , Imagem por Ressonância Magnética , Imagem Molecular/métodos , Angiotensina II , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Ruptura Aórtica/induzido quimicamente , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/metabolismo , Ruptura Aórtica/patologia , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/patologia , Estudos de Viabilidade , Gadolínio DTPA/análogos & derivados , Masculino , Camundongos Knockout para ApoE , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo
20.
Lab Anim ; 53(1): 53-62, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29788793

RESUMO

Early death of mouse pups is a commonly known problem in breeding mice colonies, which is still often regarded as 'normal' or is even overlooked due to the counting procedures applied. As reduced breeding performance probably indicates reduced well-being, this seems to be an underestimated welfare issue in laboratory mouse breeding. The present study compares the influence of three different forms of enrichment in breeding cages on infant survival rate and development of C57BL/6J mice. Our data reveal that lack of enrichment results in greater preweaning pup mortality, reduced weight and delayed development. Changing the environmental conditions after birth cannot prevent litter loss but improves the development of pups born in impoverished environments. Overall, our results underline the importance of early counting of mice for optimizing refinement strategies to ensure well-being and breeding success.


Assuntos
Bem-Estar do Animal , Animais de Laboratório/fisiologia , Camundongos/fisiologia , Mortalidade Perinatal , Animais , Animais Recém-Nascidos/fisiologia , Humanos , Camundongos Endogâmicos C57BL , Fatores de Risco
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