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Sample records for vivo animal study

  1. In Vivo Assessment of Muscle Contractility in Animal Studies.

    Science.gov (United States)

    Iyer, Shama R; Valencia, Ana P; Hernández-Ochoa, Erick O; Lovering, Richard M

    2016-01-01

    In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Animal models provide unmitigated access to histological samples, which provide a "direct measure" of damage. However, even with unconstrained access to tissue morphology and biochemistry assays, the findings typically do not account for loss of muscle function. Thus, the most comprehensive measure of the overall health of the muscle is assessment of its primary function, which is to produce contractile force. The majority of animal models testing contractile force have been limited to the muscle groups moving the ankle, with advantages and disadvantages depending on the equipment. Here, we describe in vivo methods to measure torque, to produce a reliable muscle injury, and to follow muscle function within the same animal over time. We also describe in vivo methods to measure tension in the leg and thigh muscles.

  2. In Vivo Assessment of Muscle Contractility in Animal Studies

    OpenAIRE

    Iyer, Shama R.; Valencia, Ana P.; Hern?ndez-Ochoa, Erick O.; Richard M Lovering

    2016-01-01

    In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Animal models provide unmitigated access to histological samples, which provide a ?direct measure? of damage. However, even with unconstrained access to tissue morphology and biochemistry assays, the findings typically do not account for loss of muscle function. Thus, the most comprehensive meas...

  3. Fiducial markers for MR histological correlation in ex vivo or short-term in vivo animal experiments: a screening study.

    Science.gov (United States)

    Rouvière, Olivier; Reynolds, Carol; Le, Yuan; Lai, Jinping; Roberts, Lewis R; Felmlee, Joel P; Ehman, Richard L

    2006-01-01

    To test injectable fiducial markers for magnetic resonance (MR) histological correlation in ex vivo or in vivo animal experiments. A total of 35 potential markers were tested ex vivo in pork muscle. The end-points were: 1) visibility, size, and shape on MR images and at macroscopic examination; 2) 24-hour stability; and 3) microscopic appearance. Selected markers were injected in vivo (rabbit's muscle and breast tumor tissue) to test their three-hour in vivo stability and their potential toxicity. Finally, different dilutions of the two best markers were assessed again through the same screening tests to determine whether their size on MR images could be customized by dilution. Two fluid acrylic paints containing inorganic pigments were found to be potentially interesting markers. On MR images, they created well-defined susceptibility artifacts. The markers made with iridescent bronze paint (iron oxide coated mica particles) were readily visible on microscopy and their size on MR images could be customized by dilution. The iridescent stainless steel paint (iron, chromium, nickel) created ex vivo the smallest markers in tissue but needed colloidal iron staining to be visible on microscopy and could not be easily diluted. Fluid acrylic paints are potentially interesting markers for MR histological correlation. Further studies are needed to assess their long-term properties.

  4. Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke

    2013-01-01

    Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

  5. A review of in vivo animal studies in retinal prosthesis research.

    Science.gov (United States)

    Bertschinger, Dimiter R; Beknazar, Evgueny; Simonutti, Manuel; Safran, Avinoam B; Sahel, José A; Rosolen, Serge G; Picaud, Serge; Salzmann, Joel

    2008-11-01

    The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15 years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18). The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving field.

  6. Drosophila melanogaster as an animal model for the study of Pseudomonas aeruginosa biofilm infections in vivo.

    Directory of Open Access Journals (Sweden)

    Heidi Mulcahy

    2011-10-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3 demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo.

  7. The use of planarians as in vivo animal model to study laser biomodulation effects

    Science.gov (United States)

    Munin, Egberto; Garcia, Neila Maria Rocha; Braz, Allison Gustavo; de Souza, Sandra Cristina; Alves, Leandro Procópio; Salgado, Miguel Angel Castillo; Pilla, Viviane

    2007-02-01

    A variety of effects is attributed to the photo stimulation of tissues, such as improved healing of ulcers, analgesic and anti-inflammatory effects, stimulation of the proliferation of cells of different origins and stimulation of bone repair. Some investigations that make qualitative evaluations, like wound healing and evaluation of pain and edema, can be conducted in human subjects. However, deeper investigations on the mechanisms of action of the light stimulus and other quantitative works that requires biopsies or destructive analysis has to be carried out in animal models or in cell cultures. In this work, we propose the use of planarians as a model to study laser-tissue interaction. Contrasting with cell cultures and unicellular organisms, planarians are among the simplest organism having tissue layers, central nerve system, digestive and excretory system that might have been platforms for the evolution of the complex and highly organized tissues and organs found in higher organisms. For the present study, 685 nm laser radiation was employed. Planarians were cut transversally, in a plane posterior to the auricles. The body fragments were left to regenerate and the proliferation dynamics of stem cells was studied by using histological analysis. Maximum cell count was obtained for the laser treated group at the 4 th experimental day. At that experimental time, we also had the largest difference between the irradiated and the non-irradiated control group. We concluded that the studied flatworm could be an interesting animal model for in vivo studies of laser-tissue interactions.

  8. Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study

    Science.gov (United States)

    Mahmoud, Ahmed M.; Ding, Xuan; Dutta, Debaditya; Singh, Vijay P.; Kim, Kang

    2014-02-01

    sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic curve was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis.

  9. Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies

    Science.gov (United States)

    Bazyar, Soha; Inscoe, Christina R.; O’Brian, E. Timothy; Zhou, Otto; Lee, Yueh Z.

    2017-12-01

    Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200–1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size  ≈  4  ×  10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM  =  246  ±  32 µm center-to-center  =  926  ±  23 µm peak-to-valley dose ratio  =  24.35  ±  2.10 collimator relative output factor  =  0.84  ±  0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP  =  glioblastoma B16-F10  =  melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p  <  0.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in vivo (mouse brain tissue) and up to 10 cm deep in the radiochromic film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the

  10. In vivo conservation of animal genetic resources

    NARCIS (Netherlands)

    Boettcher, P.; Martin, J.F.; Gandini, G.; Joshi, B.K.; Oldenbroek, J.K.

    2013-01-01

    These guidelines present the basic concepts involved in the development and implementation of in vivo conservation plans for animal genetic resources for food and agriculture. The guidelines are intended for use by policy-makers in the management of animal genetic resources, managers of animal

  11. A New Step Toward Evidence of In Vivo Perineural Dexamethasone Safety: An Animal Study.

    Science.gov (United States)

    Marty, Philippe; Bennis, Mehdi; Legaillard, Benjamin; Cavaignac, Etienne; Ferre, Fabrice; Lebon, Julie; Brouchet, Anne; Minville, Vincent

    2017-04-07

    The aim of this study was to analyze histological nerve toxicity of perineural dexamethasone administration in combination with ropivacaine on mice. Efficacy of perineural dexamethasone in combination with regional anesthesia is clearly demonstrated. However, the safety of this procedure is still a matter of debate. A sciatic nerve block was performed on 90 mice. Five groups, each containing 18 mice assigned randomly, were used in these experiments: the sham group (isotonic saline solution), R group (perineural ropivacaine), D group (perineural dexamethasone), RDPN group (perineural ropivacaine and perineural dexamethasone), and the RDS group (perineural ropivacaine and systemic dexamethasone). Sensory and motor blocks were evaluated every 30 minutes for 14 hours. Fourteen and 28 days after this procedure, 9 mice in each group were killed for sciatic nerve histological assessment. No statistical difference was observed between different groups for Wallerian degeneration (P = 0.28 at day 14 and P = 0.22 at day 28) and perineural inflammation (P = 0.9 at day 14). Motor and sensory block durations were tested for each group. A statistical difference was observed for motor block duration between the RDPN group (150 minutes [127-172 minutes]), the RDS group (120 minutes [90-120 minutes]), and the R group (60 minutes [60-90 minutes]). Sensory block duration was also statistically different: 660 minutes (660-720 minutes) in the RDPN group, 480 minutes (427-660 minutes) in RDS group, 330 minutes (240-410) in the R group. A combination of ropivacaine and perineural dexamethasone allows longer sensory block duration compared with ropivacaine alone or ropivacaine and systemic dexamethasone, without increased neural toxicity.

  12. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

    Science.gov (United States)

    Inglés, M.; Olaso, G.; Lopez-Grueso, R.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K. M.; Gomez-Cabrera, M. C.; Vina, J.; Borras, C.

    2015-01-01

    Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol. PMID:26221416

  13. Comparison between Different Methods for Biomechanical Assessment of Ex Vivo Fracture Callus Stiffness in Small Animal Bone Healing Studies

    Science.gov (United States)

    Steiner, Malte; Volkheimer, David; Meyers, Nicholaus; Wehner, Tim; Wilke, Hans-Joachim; Claes, Lutz; Ignatius, Anita

    2015-01-01

    For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to 16.8%, compared to corresponding alignment under unconstrained torsion) due to a parallel offset between the specimens’ axis of gravity and the torsional

  14. Comparison between different methods for biomechanical assessment of ex vivo fracture callus stiffness in small animal bone healing studies.

    Science.gov (United States)

    Steiner, Malte; Volkheimer, David; Meyers, Nicholaus; Wehner, Tim; Wilke, Hans-Joachim; Claes, Lutz; Ignatius, Anita

    2015-01-01

    For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to 16.8%, compared to corresponding alignment under unconstrained torsion) due to a

  15. Comparison between different methods for biomechanical assessment of ex vivo fracture callus stiffness in small animal bone healing studies.

    Directory of Open Access Journals (Sweden)

    Malte Steiner

    Full Text Available For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior. The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS, mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%, however small angular deviations (<15° were negligible. Differences in the experimental results between the bending tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small

  16. FMT-XCT: in vivo animal studies with hybrid fluorescence molecular tomography-X-ray computed tomography.

    Science.gov (United States)

    Ale, Angelique; Ermolayev, Vladimir; Herzog, Eva; Cohrs, Christian; de Angelis, Martin Hrabé; Ntziachristos, Vasilis

    2012-06-01

    The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360° imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.

  17. Macroscopic and Histological Evaluations of Meniscal Allograft Transplantation Using Gamma Irradiated Meniscus: A Comparative in Vivo Animal Study

    Directory of Open Access Journals (Sweden)

    Jin Zhang

    2015-01-01

    significant higher ICRS scores and Mankin scores than both the 0 Mrad group and the 1.5 Mrad group (P < 0.05. Whereas the 1.5 Mrad group presented similar results to the 0 Mrad group concerning both the ICRS scores and the Mankin scores. Conclusions: The current in vivo animal study proved that although the meniscal collagen fibers were damaged after gamma irradiation, the failure rate of MAT surgeries might not significantly increase if the irradiation dose was <1.5 Mrad for New Zealand white rabbits.

  18. A rapid method for selecting suitable animal species for studying pathogen interactions with plasma protein ligands in vivo.

    Science.gov (United States)

    Naudin, Clément; Schumski, Ariane; Salo-Ahen, Outi M H; Herwald, Heiko; Smeds, Emanuel

    2017-05-01

    Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb to human fibrinogen and human C3 was studied. Affinity experiments and Western blot analyses were used to validate the assay. Human, monkey and cat plasma interfered with binding of SSL7 to human C5. Binding of Efb to human fibrinogen was blocked in human, monkey, gerbil and pig plasma, while human, monkey, gerbil, rabbit, cat and guinea pig plasma inhibited the binding of Efb to human C3. These results emphasize the importance of choosing correct animal models, and thus, our approach is a rapid and cost-effective method that can be used to prevent unnecessary animal experiments. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  19. Establishment study of the in vivo imaging analysis with small animal imaging modalities for bio-durg development

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Beomsu; Park, Sanghyeon; Choi, Dae Seong; Park, Jeonghoon; Jung, Uhee; Lee, Yun Jong

    2012-01-15

    In this study, we established the image modalities (micro-PET, SPECT/CT) using the experimental animal (mouse) for the development of imaging assessment method for the bio-durg and extramural collaboration proposal. We examined the micro-SPECT/CT, PET imaging study using the Siemens Inveon micro-multimodality system (SPECT/CT) and imaging study using the Siemens Inveon micro-multimodality system (SPECT/CT) and micro-PET with {sup 99m}Tc tricarbonyl bifunctional chelators and {sup 18}F-clotrimazole derivative. SPECT imaging studies were performed with {sup 99m}Tc tricarbonyl BFCs. PET imaging study was performed with {sup 18}F-clotrimazole derivatives. We performed the PET image study of {sup 18}F-clotrimazole derivatives using U87MG tumor bearing mice. Also we tested the intramural and extramural collaboration using small animal imaging modalities and prepared the draft of extramural R and D operation manual for small animal imaging modalities and the experimental animal imaging facility. These research results can be utilized as a basic image study protocols and data for the image assessment of drugs including biological drug.

  20. In-vivo corneal pulsation in relation to in-vivo intraocular pressure and corneal biomechanics assessed in-vitro. An animal pilot study.

    Science.gov (United States)

    Rogala, Maja M; Danielewska, Monika E; Antończyk, Agnieszka; Kiełbowicz, Zdzisław; Rogowska, Marta E; Kozuń, Marta; Detyna, Jerzy; Iskander, D Robert

    2017-09-01

    The aim was to ascertain whether the characteristics of the corneal pulse (CP) measured in-vivo in a rabbit eye change after short-term artificial increase of intraocular pressure (IOP) and whether they correlate with corneal biomechanics assessed in-vitro. Eight New Zealand white rabbits were included in this study and were anesthetized. In-vivo experiments included simultaneous measurements of the CP signal, registered with a non-contact method, IOP, intra-arterial blood pressure, and blood pulse (BPL), at the baseline and short-term elevated IOP. Afterwards, thickness of post-mortem corneas was determined and then uniaxial tensile tests were conducted leading to estimates of their Young's modulus (E). At the baseline IOP, backward stepwise regression analyses were performed in which successively the ocular biomechanical, biometric and cardiovascular predictors were separately taken into account. Results of the analysis revealed that the 3rd CP harmonic can be statistically significantly predicted by E and central corneal thickness (Models: R2 = 0.662, p biomechanics in-vitro was confirmed. In particular, spectral analysis revealed that higher amplitude and power of the 3rd CP harmonic indicates higher corneal stiffness, while the 1st CP harmonic correlates positively with the corresponding harmonic of the BPL signal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Draft guidelines on in vivo conservation of animal genetic resources

    OpenAIRE

    Boettcher, P.; Martin, J.F.; Gandini, G.; Joshi, B.K.; Oldenbroek, J.K.; Sponenberg, P.

    2012-01-01

    These guidelines present the basic concepts involved in the establishment and implementation of in vivo conservation plans for animal genetic resources for food and agriculture. The guidelines are intended for use by policy makers in the management of animal genetic resources, managers of animal breeding organizations, persons responsible for training in animal genetic resource management and any stakeholders with a leading role in designing and implementing in vivo conservation of animal gen...

  2. In Vivo Monitoring of the Antiangiogenic Effect of Neurotensin Receptor-Mediated Radiotherapy by Small-Animal Positron Emission Tomography: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Simone Maschauer

    2014-04-01

    Full Text Available The neurotensin receptor (NTS1 has emerged as an interesting target for molecular imaging and radiotherapy of NTS-positive tumors due to the overexpression in a range of tumors. The aim of this study was to develop a 177Lu-labeled NTS1 radioligand, its application for radiotherapy in a preclinical model and the imaging of therapy success by small-animal positron emission tomography (µPET using [68Ga]DOTA-RGD as a specific tracer for imaging angiogenesis. The 177Lu-labeled peptide was subjected to studies on HT29-tumor-bearing nude mice in vivo, defining four groups of animals (single dose, two fractionated doses, four fractionated doses and sham-treated animals. Body weight and tumor diameters were determined three times per week. Up to day 28 after treatment, µPET studies were performed with [68Ga]DOTA-RGD. At days 7–10 after treatment with four fractionated doses of 11–14 MBq (each at days 0, 3, 6 and 10, the tumor growth was slightly decreased in comparison with untreated animals. Using a single high dose of 51 MBq, a significantly decreased tumor diameter of about 50% was observed with the beginning of treatment. Our preliminary PET imaging data suggested decreased tumor uptake values of [68Ga]DOTA-RGD in treated animals compared to controls at day 7 after treatment. This pilot study suggests that early PET imaging with [68Ga]DOTA-RGD in radiotherapy studies to monitor integrin expression could be a promising tool to predict therapy success in vivo. Further successive PET experiments are needed to confirm the significance and predictive value of RGD-PET for NTS-mediated radiotherapy.

  3. Brain Activity of Thioctic Acid Enantiomers: In Vitro and in Vivo Studies in an Animal Model of Cerebrovascular Injury

    Directory of Open Access Journals (Sweden)

    Seyed Khosrow Tayebati

    2013-02-01

    Full Text Available Oxidative stress is an imbalance between the production of free radicals and antioxidant defense mechanisms, potentially leading to tissue damage. Oxidative stress has a key role in the development of cerebrovascular and/or neurodegenerative diseases. This phenomenon is mainly mediated by an enhanced superoxide production by the vascular endothelium with its consequent dysfunction. Thioctic, also known as alpha-lipoic acid (1,2-dithiolane-3-pentanoic acid, is a naturally occurring antioxidant that neutralizes free radicals in the fatty and watery regions of cells. Both the reduced and oxidized forms of the compound possess antioxidant ability. Thioctic acid has two optical isomers designated as (+- and (−-thioctic acid. Naturally occurring thioctic acid is the (+-thioctic acid form, but the synthetic compound largely used in the market for stability reasons is a mixture of (+- and (−-thioctic acid. The present study was designed to compare the antioxidant activity of the two enantiomers versus the racemic form of thioctic acid on hydrogen peroxide-induced apoptosis in a rat pheochromocytoma PC12 cell line. Cell viability was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and free oxygen radical species (ROS production was assessed by flow cytometry. Antioxidant activity of the two enantiomers and the racemic form of thioctic acid was also evaluated in spontaneously hypertensive rats (SHR used as an in vivo model of increased oxidative stress. A 3-h exposure of PC12 cells to hydrogen peroxide (H2O2 significantly decreased cell viability and increased levels of intracellular ROS production. Pre-treatment with racemic thioctic acid or (+-enantiomer significantly inhibited H2O2-induced decrease in cell viability from the concentration of 50 μmol/L and 20 μmol/L, respectively. Racemic thioctic acid and (+-salt decreased levels of intracellular ROS, which were unaffected by (−-thioctic acid. In the brain of

  4. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo

    DEFF Research Database (Denmark)

    Verhagen, H.; Aruoma, O.I.; van Delft, J.H.M.

    2003-01-01

    , provided they can be justified on scientific grounds. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo concern the following areas: (1) Hypothesis-driven study design; (2......There is increasing evidence that chemicals/test substances cannot only have adverse effects, but that there are many substances that can (also) have a beneficial effect on health. As this journal regularly publishes papers in this area and has every intention in continuing to do so in the near...... future, it has become essential that studies reported in this journal reflect an adequate level of scientific scrutiny. Therefore a set of essential characteristics of studies has been defined. These basic requirements are default properties rather than non-negotiables: deviations are possible and useful...

  5. Non-Invasive in vivo Imaging in Small Animal Research

    Directory of Open Access Journals (Sweden)

    V. Koo

    2006-01-01

    Full Text Available Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI, Computed Tomography (CT, Positron Emission Tomography (PET, bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

  6. Draft guidelines on in vivo conservation of animal genetic resources

    NARCIS (Netherlands)

    Boettcher, P.; Martin, J.F.; Gandini, G.; Joshi, B.K.; Oldenbroek, J.K.; Sponenberg, P.

    2012-01-01

    These guidelines present the basic concepts involved in the establishment and implementation of in vivo conservation plans for animal genetic resources for food and agriculture. The guidelines are intended for use by policy makers in the management of animal genetic resources, managers of animal

  7. Use of Carbapenems against clinical, nontyphoid Salmonella isolates: results from in vitro and in vivo animal studies.

    Science.gov (United States)

    Tang, Hung-Jen; Chen, Chi-Chung; Zhang, Chun-Cheng; Cheng, Kuo Chen; Chiang, Shyh-Ren; Chiu, Yu-Hsin; Ku, Yee Huang; Ko, Wen-Chien; Chuang, Yin-Ching

    2012-06-01

    The emergence of multidrug-resistant Salmonella isolates has created the need for new therapeutic agents. We evaluated the intracellular activity of four carbapenem compounds against clinical nontyphoid Salmonella (NTS) isolates in vitro and ex vivo. Subsequently, the efficacy of carbapenem treatment against selected Salmonella isolates in vivo was assessed using a murine peritonitis model. The MIC(50) and MIC(90) for doripenem, ertapenem, imipenem, and meropenem against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5 and 1, and 0.031 and 0.031 μg/ml, respectively. The intracellular killing effect of ertapenem was sustained for 24 h and was superior to that of imipenem, meropenem, and doripenem; its effect was comparable to that of ceftriaxone. Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio of 20,733. When peritoneal exudate cells were examined directly ex vivo from mice with Salmonella-induced peritonitis, cells from mice treated with ertapenem and ceftriaxone had intracellular and extracellular bacterial counts reduced 10(2)- to 10(4)-fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 × 10(5) and 10(6) CFU of a ceftriaxone-susceptible Salmonella isolate that were subsequently treated with ertapenem or ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 × 10(4) and 10(5) CFU of a ceftriaxone-resistant and ciprofloxacin-resistant Salmonella isolate, mice treated with ertapenem had a higher survival rate than mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively; P Salmonella infections and show that further clinical investigations on the potential use of ertapenem in treatment of human Salmonella infections are warranted.

  8. Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study.

    Science.gov (United States)

    Struss, Werner J; Tan, Zheng; Zachkani, Payam; Moskalev, Igor; Jackson, John K; Shademani, Ali; D'Costa, Ninadh M; Raven, Peter A; Frees, Sebastian; Chavez-Munoz, Claudia; Chiao, Mu; So, Alan I

    2017-05-01

    The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrating a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts received docetaxel (10 mg/kg) either subcutaneously (SC) or intravenously (IV) and the fourth cohort was treated using the magnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5 μg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using ultrasound. In addition, calipers were used to assess tumor volume. Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemic symptoms of inflammation and infection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that the mean tumor growth rate of our device cohort was significantly lower than SC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in the MADDD treated tumors and a decreased proliferation when compared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight

  9. Study and development of a high resolution tomograph for the {gamma} radio-imagery in vivo of small animals; Etude et developpement d`un tomographe haute resolution pour la radio-imagerie {gamma} in vivo de petits animaux

    Energy Technology Data Exchange (ETDEWEB)

    Valda Ochoa, A.

    1995-06-23

    By the use of molecular radio-labelled tracers, molecular biology can reveal some aspects of the functional organisation of the brain. Non invasive in vivo brain research on small laboratory animals, like mice or rats, require analysis of structures of some cubic millimeters present in a brain of the order of a cubic centimeter. Since imaging performances of positron emission tomography (PET) and single photon emission tomography (SPECT) fail in this research field, we present here a high resolution tomograph (TOHR) based on an original principle that allows to overcome the compromise between detection efficiency and spatial resolution. TOHR is a radiation counter device having a large solid angle focusing collimator. By the use of radio-tracers decaying by a cascade of two photons, coincidence detection offers an accurate delimitation of the analysed region and improves spatial resolution. TOHR acts as a scanner, so the image is built voxel by voxel by moving the animal relative to the detector. A numerical feasibility study of such a system shows that a sub millimeter spatial resolution can be achieved. We show that the chemical etching technique is well suited for manufacturing a multi-module focusing collimator by building and testing two such modules. Finally a numerical simulation exhibits TOHR`s performance in a neuro-pharmacological experiment on a rat. From these results, other application of TOHR are envisaged, such as oncology (in vivo evolution of tumours) or gene therapy (distribution of viral particles in the brain). (author). 51 refs., 73 figs., 3 tabs.

  10. In vitro and in vivo studies with [{sup 18}F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor

    Energy Technology Data Exchange (ETDEWEB)

    Nejjari, Mimoun [Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon (France); Laboratoire CREATIS-ANIMAGE UMR 5515 Cnrs-U630 Inserm-Insa de Lyon (France); Inserm U865, Faculte de Medecine RTH Laennec, 69008 Lyon (France); Kryza, David [Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon (France); Universite Lyon 1, Federation Sante, Domaine Rockefeller, 69008 Lyon (France); Poncet, Gilles [Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon (France); Inserm U865, Faculte de Medecine RTH Laennec, 69008 Lyon (France); Roche, Colette [Inserm U865, Faculte de Medecine RTH Laennec, 69008 Lyon (France); Perek, Nathalie [Departement de Biophysique, Faculte de Medecine J. Lisfranc, 42023 Saint-Etienne (France); Chayvialle, Jean-Alain [Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon (France); Inserm U865, Faculte de Medecine RTH Laennec, 69008 Lyon (France); Universite Lyon 1, Federation Sante, Domaine Rockefeller, 69008 Lyon (France); Le Bars, Didier [Universite Lyon 1, Federation Sante, Domaine Rockefeller, 69008 Lyon (France); CERMEP, 59 Boulevard Pinel, 69677 Bron Cedex (France); Scoazec, Jean-Yves [Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon (France); Inserm U865, Faculte de Medecine RTH Laennec, 69008 Lyon (France); Universite Lyon 1, Federation Sante, Domaine Rockefeller, 69008 Lyon (France); Janier, Marc [Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon (France); Laboratoire CREATIS-ANIMAGE UMR 5515 Cnrs-U630 Inserm-Insa de Lyon (France); Universite Lyon 1, Federation Sante, Domaine Rockefeller, 69008 Lyon (France); Borson-Chazot, Francoise [Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon (France); Universite Lyon 1, Federation Sante, Domaine Rockefeller, 69008 Lyon (France); Inserm U664, Faculte de Medecine RTH Laennec, 69008 Lyon (France)], E-mail: francoise.borson-chazot@chu-lyon.fr

    2008-01-15

    Purpose: The aim of this study was to investigate (a) in vitro the relationship between [{sup 18}F]fluorocholine ([{sup 18}F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [{sup 18}F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [{sup 18}F]FCH and that of [{sup 18}F]fluorodeoxyglucose ([{sup 18}F]FDG) were measured before and after cytotoxic therapy. [{sup 18}F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [{sup 18}F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC{sub 50} values calculated with the [{sup 18}F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [{sup 18}F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [{sup 18}F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [{sup 18}F]FCH in liver metastases but there was a significant uptake of [{sup 18}F]FDG. Conclusions: In vitro studies suggested that the incorporation of [{sup 18}F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [{sup 18}F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [{sup 18}F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded.

  11. In vitro and in vivo study of microporous ceramics using MC3T3 cells, CAM assay and a pig animal model.

    Science.gov (United States)

    Tomco, Marek; Petrovova, Eva; Giretova, Maria; Almasiova, Viera; Holovska, Katarina; Cigankova, Viera; Jenca, Andrej; Jencova, Janka; Jenca, Andrej; Boldizar, Martin; Balazs, Kosa; Medvecky, Lubomir

    2017-09-01

    Bone tissue engineering combines biomaterials with biologically active factors and cells to hold promise for reconstructing craniofacial defects. In this study the biological activity of biphasic hydroxyapatite ceramics (HA; a bone substitute that is a mixture of hydroxyapatite and β-tricalcium phosphate in fixed ratios) was characterized (1) in vitro by assessing the growth of MC3T3 mouse osteoblast lineage cells, (2) in ovo by using the chick chorioallantoic membrane (CAM) assay and (3) in an in vivo pig animal model. Biocompatibility, bioactivity, bone formation and biomaterial degradation were detected microscopically and by radiology and histology. HA ceramics alone demonstrated great biocompatibility on the CAM as well as bioactivity by increased proliferation and alkaline phosphatase secretion of mouse osteoblasts. The in vivo implantation of HA ceramics with bone marrow mesenchymal stem cells (MMSCs) showed de novo intramembranous bone healing of critical-size bone defects in the right lateral side of pig mandibular bodies after 3 and 9 weeks post-implantation. Compared with the HA ceramics without MMSCs, the progress of bone formation was slower with less-developed features. This article highlights the clinical use of microporous biphasic HA ceramics despite the unusually shaped elongated micropores with a high length/width aspect ratio (up to 20) and absence of preferable macropores (>100 µm) in bone regenerative medicine.

  12. Application of Voxel Phantoms to Study the Influence of Heterogeneous Distribution of Actinides in Lungs on In Vivo Counting Calibration Factors Using Animal Experimentations

    Energy Technology Data Exchange (ETDEWEB)

    Lamart, S.; Pierrat, N.; De Carlan, L.; Franck, D. [IRSN/DRPH/SDI/LEDI, BP 17, F-92 262 Fontenay-aux-Roses (France); Dudoignon, N. [IRSN/DRPH/SRBE/LRPAT, BP 17, F-92 262 Fontenay-aux-Roses (France); Rateau, S.; Van der Meeren, A.; Rouit, E. [CEA/DSV/DRR/SRCA/LRT BP no 12, F-91680 Bruyeres-le-Chatel (France); Bottlaender, M. [CEA/SHFJ, 4, place du General Leclerc F-91400 Orsay (France)

    2006-07-01

    Calibration of lung counting system dedicated to retention assessment of actinides in the lungs remains critical due to large uncertainties in calibration factors. Among them, the detector positioning, the chest wall thickness and composition (muscle/fat) assessment, and the distribution of the contamination are the main parameters influencing the detector response. In order to reduce these uncertainties, a numerical approach based on the application of voxel phantoms (numerical phantoms based on tomographic images, CT or MRI) associated to a Monte-Carlo code (namely M.C.N.P.) was developed. It led to the development of a dedicated tool, called O.E.D.I.P.E., that allows to easily handle realistic voxel phantoms for the simulation of in vivo measurement (or dose calculation, application that will not be presented in this paper). The goal of this paper is to present our study of the influence of the lung distribution on calibration factors using both animal experimentations and our numerical method. Indeed, physical anthropomorphic phantoms used for calibration always consider a uniform distribution of the source in the lungs, which is not true in many contamination conditions. The purpose of the study is to compare the response of the measurement detectors using a real distribution of actinide particles in the lungs, obtained from animal experimentations, with the homogeneous one considered as the reference. This comparison was performed using O.E.D.I.P.E. that can almost simulate any source distribution. A non human primate was contaminated heterogeneously by intra-tracheal administration of actinide oxide. After euthanasia, gamma spectrometry measurements were performed on the pulmonary lobes to obtain the distribution of the contamination in the lungs. This realistic distribution was used to simulate an heterogeneous contamination in the numerical phantom of the non human primate, which was compared with a simulation of an homogeneous contamination presenting the

  13. Partial renal resection by LaparoNewPro: in vivo open and laparoscopic study in an animal model.

    Science.gov (United States)

    Rossi, Piero; Montuori, Mauro; Bove, Pierluigi; De Majo, Adriano; Ricciardi, Edoardo; Mattei, Maurizio; Bernardini, Roberta; Calzetta, Luigino; Mauti, Paolo; Intini, Lorenzo; Quattrini, Valentino; Chiaramonte, Carlo; Mauriello, Alessandro; Vespasiani, Giuseppe

    2017-12-01

    The aim of this research project was to test an incremental bipolar radiofrequency generator with open and laparoscopic inline electrode probe for partial renal resection without vascular clamping. Sixteen polar resections with clamping and six without were performed in four pigs in the acute phase. Three pigs underwent laparoscopic polar resection and were live housed for ten days and reoperated to verify the presence of hematic and urinary collection and the condition of the renal edge. Five pigs underwent laparoscopic polar resection without clamping, and two of these were live housed and reoperated after ten days. Polar renal resection by our system (LaparoNewPro) turned out to be effective and safe, without cardio-respiratory complications or damage to the remaining parenchyma. Coagulation of the renal parenchyma before resection is effective and safe; at the reoperation, no complications were observed. The laparoscopic version of the probe is ergonomic and safe, with effective coagulation and a small amount of smoke produced. No complications occurred in the housed animals. No damage, local or to residual parenchyma, or thrombosis of the renal vessels were found. LaparoNewPro is able to deliver coagulation of the resection line effectively and independently of clamping of the vessels both in the open and laparoscopic approaches. Coagulation times are short, the automatism of the generator is reliable, and the open and laparoscopic probes are ergonomic.

  14. Case Experience of Radiofrequency Ablation for Benign Thyroid Nodules: From an Ex Vivo Animal Study to an Initial Ablation in Taiwan

    Directory of Open Access Journals (Sweden)

    Ming-Tsang Lee

    2016-03-01

    Full Text Available Radiofrequency ablation (RFA is a minimally invasive technique, used with ultrasound or computed tomography guidance, which can produce tissue coagulation necrosis in various kinds of tumors in the human body. In the past 10 years, numerous studies about RFA in benign thyroid nodules have been published. Reviewing these studies, we noticed that the effectiveness of ablation was higher when it was performed with the “moving-shot technique” via an internally cooled electrode. A consensus statement published from the Korean Society of Radiology also suggested the moving-shot technique as a standard ablation procedure for benign thyroid nodule ablation in Korea. In Taiwan, most symptomatic benign nodules are currently treated with surgical removal. RFA for mass lesions is primarily performed for the treatment of metastatic hepatic tumors. In our case, we have attempted to introduce RFA for benign thyroid nodules in Taiwan. Because endocrinologists in Taiwan were not familiar with this technique, we adopted a stepwise approach in learning how to perform RFA. We conducted ex vivo animal ablation exercises to gain experience in setting the radiofrequency generator for the right ablation mode and appropriate power output. The thyroid nodule volume reduction rate after 1 year of follow up was approximately 50% in this case. The most important thing we learned from this trial is that we confirmed the safety of thyroid nodule ablation. To the best of our knowledge, this is the first reported study of RFA of a thyroid nodule in Taiwan.

  15. In vivo small animal imaging: Current status and future prospects

    Energy Technology Data Exchange (ETDEWEB)

    Kagadis, George C., E-mail: gkagad@gmail.com, E-mail: george.kagadis@med.upatras.gr [Department of Medical Physics, School of Medicine, University of Patras, P.O. BOX 132 73, GR 265 04 Rion, Greece and Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (United States); Loudos, George [Department of Medical Instruments Technology, Technological Educational Institute of Athens, 28 Ag. Spyridonos Street, GR 122 10 Egaleo (Greece); Katsanos, Konstantinos [Department of Radiology, School of Medicine, University of Patras, GR 265 04 Rion (Greece); Langer, Steve G. [Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (United States); Nikiforidis, George C. [Department of Medical Physics, School of Medicine, University of Patras, GR 265 04 Rion (Greece)

    2010-12-15

    The use of small animal models in basic and preclinical sciences constitutes an integral part of testing new pharmaceutical agents prior to commercial translation to clinical practice. Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. Biomedical imaging is now listed along with genomics, proteomics, and metabolomics as an integral part of biological and medical sciences. Miniaturized versions of clinical diagnostic modalities, including but not limited to microcomputed tomography, micromagnetic resonance tomography, microsingle-photon-emission tomography, micropositron-emission tomography, optical imaging, digital angiography, and ultrasound, have all greatly improved our investigative abilities to longitudinally study various experimental models of human disease in mice and rodents. After an exhaustive literature search, the authors present a concise and critical review of in vivo small animal imaging, focusing on currently available modalities as well as emerging imaging technologies on one side and molecularly targeted contrast agents on the other. Aforementioned scientific topics are analyzed in the context of cancer angiogenesis and innovative antiangiogenic strategies under-the-way to the clinic. Proposed hybrid approaches for diagnosis and targeted site-specific therapy are highlighted to offer an intriguing glimpse of the future.

  16. In vivo small animal imaging: current status and future prospects.

    Science.gov (United States)

    Kagadis, George C; Loudos, George; Katsanos, Konstantinos; Langer, Steve G; Nikiforidis, George C

    2010-12-01

    The use of small animal models in basic and preclinical sciences constitutes an integral part of testing new pharmaceutical agents prior to commercial translation to clinical practice. Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. Biomedical imaging is now listed along with genomics, proteomics, and metabolomics as an integral part of biological and medical sciences. Miniaturized versions of clinical diagnostic modalities, including but not limited to microcomputed tomography, micromagnetic resonance tomography, microsingle-photon-emission tomography, micropositron-emission tomography, optical imaging, digital angiography, and ultrasound, have all greatly improved our investigative abilities to longitudinally study various experimental models of human disease in mice and rodents. After an exhaustive literature search, the authors present a concise and critical review of in vivo small animal imaging, focusing on currently available modalities as well as emerging imaging technologies on one side and molecularly targeted contrast agents on the other. Aforementioned scientific topics are analyzed in the context of cancer angiogenesis and innovative antiangiogenic strategies under-the-way to the clinic. Proposed hybrid approaches for diagnosis and targeted site-specific therapy are highlighted to offer an intriguing glimpse of the future.

  17. In vivo imaging of small animal models by photoacoustic microscopy

    Science.gov (United States)

    Ye, Shuoqi; Yang, Ran; Xiong, Jingwei; Shung, K. Kirk; Zhou, Qifa; Li, Changhui; Ren, Qiushi

    2012-02-01

    Small animal models, such as zebrafish, drosophila, C. elegan, is considered to be important models in comparative biology and diseases researches. Traditional imaging methods primarily employ several optical microscopic imaging modalities that rely on fluorescence labeling, which may have potential to affect the natural physiological progress. Thus a label-free imaging method is desired. Photoacoustic (PA) microscopy (PAM) is an emerging biomedical imaging method that combines optical contrast with ultrasonic detection, which is highly sensitive to the optical absorption contrast of living tissues, such as pigments, the vasculature and other optically absorbing organs. In this work, we reported the whole body label-free imaging of zebrafish larvae and drosophila pupa by PAM. Based on intrinsic optical absorption contrast, high resolution images of pigments, microvasculature and several other major organs have been obtained in vivo and non-invasively, and compared with their optical counterparts. We demonstrated that PAM has the potential to be a powerful non-invasive imaging method for studying larvae and pupa of various animal models.

  18. In vivo anti-inflammatory effects of taraxasterol against animal models

    African Journals Online (AJOL)

    This study aims to determine the in vivo anti-inflammatory effects of taraxasterol against animal models. Materials and Methods: Anti-inflammatory effects were assessed in four animal models by using dimethylbenzene-induced mouse ear edema, carrageenan-induced rat paw edema, acetic acid-induced mouse vascular ...

  19. Possibility of ex vivo animal training model for colorectal endoscopic submucosal dissection.

    Science.gov (United States)

    Yoshida, Naohisa; Yagi, Nobuaki; Inada, Yutaka; Kugai, Munehiro; Kamada, Kazuhiro; Katada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Handa, Osamu; Konishi, Hideyuki; Kokura, Satoshi; Inoue, Ken; Wakabayashi, Naoki; Abe, Yasuhisa; Yanagisawa, Akio; Naito, Yuji

    2013-01-01

    Colorectal endoscopic submucosal dissection (ESD) has not been standardized due to technical difficulties and requires extensive training for reliability. Ex vivo animal model is convenient, but has no blood flow. The objective of this study is to evaluate the characteristics of various ex vivo animal models including a blood flow model for colorectal ESD training and the usefulness of practicing endoscopic hemostasis and closure using an animal model. Harvested porcine cecum, rectum, and stomach and bovine cecum and rectum were analyzed regarding ease of mucosal injection, degree of submucosal elevation, and status of the proper muscle layer. Ex vivo animal model with blood flow was made using the bovine cecum. The vessel around the cecum was detached, and red ink was injected. Endoscopic hemostasis for perioperative hemorrhage and endoscopic closure for perforation were performed in this model. Mucosal injection was easily performed in the bovine cecum and rectum. Submucosal elevation was low in the bovine cecum, while the proper muscle layer was not tight in the porcine rectum and bovine cecum. Endoscopic hemostasis were accomplished in six (60 %) out of ten procedures of the ex vivo blood flow model. In two non-experts, the completion rates of endoscopic closure were 40 and 60 % in the first five procedures. These rates became 100 % in the last five procedures. We have evaluated the characteristics of various ex vivo animal models and shown the possibility of training for endoscopic hemostasis and endoscopic closure in the ex vivo animal model.

  20. Optimizing in vivo small animal Cerenkov luminescence imaging.

    Science.gov (United States)

    Spinelli, Antonello E; Boschi, Federico

    2012-04-01

    In vivo Cerenkov luminescence imaging is a rapidly growing molecular imaging research field based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues. We investigated theoretically the possibility of enhancing the number of the detected Cerenkov photons in the near infrared (NIR) region of the spectrum. The analysis is based on applying a photon propagation diffusion model to Cerenkov photons in the tissue. Results show that despite the smaller number of Cerenkov photons in the NIR region, the fraction exiting the tissues is greater than in the visible range, and thus, a charge-coupled device detector optimized for the NIR range will allow to obtain a higher signal. The comparison was performed considering Cerenkov point sources located at different depths inside the animal. We concluded that the improvement can be up to 35% and is more significant when the Cerenkov source to be imaged is located deeper inside the animal.

  1. Use of Adipose-Derived Stem Cells to Support Topical Skin Adhesive for Wound Closure: A Preliminary Report from Animal In Vivo Study

    Directory of Open Access Journals (Sweden)

    Maciej Nowacki

    2016-01-01

    Full Text Available The aim of this study was to determine the local and systemic effects of adipose-derived stem cells (ADSCs as a component of topical skin adhesive in an animal artificial wound closure model. In presented study the cosmetic effects, histological analysis, mechanical properties, and cell migration have been assessed to evaluate the usefulness of ADSCs as supporting factor for octyl blend cyanoacrylate adhesive. The total of 40 rats were used and divided into six groups. In the Study Group, ADSCs were administered by multipoint injection of the six surrounding intrawound areas with additional freely leaving procedure of the cells between the skin flaps just before applying adhesive to close the wound. Five control groups without using ADSCs, utilizing different types of standard wound closure, were created in order to check efficiency of experimental stem cell therapy. In our study, we proved that ADSCs could be used effectively also as a supportive tool in topical skin adhesive for wound closure. However we did not achieve any spectacular differences related to such aspects as better mechanical properties or special biological breakthroughs in wound healing properties. The use of stem cells, especially ADSCs for wound closure can provide an inspiring development in plastic and dermatologic surgery.

  2. In vivo evaluation of biofunctionalized implant surfaces with a synthetic peptide (P-15) and its impact on osseointegration. A preclinical animal study.

    Science.gov (United States)

    Schmitt, Christian M; Koepple, Markus; Moest, Tobias; Neumann, Konrad; Weisel, Tamara; Schlegel, Karl Andreas

    2016-11-01

    The overall aim of the study was to investigate a biofunctionalized implant surface with electrochemically deposition of hydroxyapatite and the synthetic peptide (P-15) and its effect on osseointegration. Three modified implant types of ANKYLOS ® C/X implants were used; (1) machined implants used as negative control (M, n = 20), (2) implants with the FRIADENT ® plus surface (grit blasted and acid-etched) used as positive control (P, n = 20), and (3) implants with a biomimetic surface consisting of hydroxyapatite and the synthetic 15 aminoacids containing peptide P-15 (BP, n = 40). The implants were randomly inserted in the mandibles of 10 beagle dogs following 4 months after tooth extraction (P1-P4). Three animals were sacrificed 2 and 7 days after implant insertion, respectively, and four animals were sacrificed 6 months post implant insertion. Bone-to-implant contacts (BICs) were analyzed via histomorphometrical analyses at five different region of interests (ROIs); two at the middle part on either side of the implant (ROI 1/4), two at the apical part of the implant at each side (ROI 2/3), and one at the tip of the implant (ROI 5). All implant surfaces showed a high level of osseointegration and osteoconductivity. The cumulative implant survival rate (CSR) was 93.8%, 100% in the M, 85% in the P, and 95% in the BP group. No statistical difference in BICs at ROI 1/4, 2/3, and 5 could be shown between implant types following 2 and 7 days of healing. BIC values increased in all groups over time. After 6 months of healing the BP group showed superiority in BIC in ROI 2/3 (73.2 ± 15.6%) compared to the P (48.3 ± 10.6%) and M group (66.3 ± 30.2%) with a significant difference between BP and P (P = 0.002). It is hypothesized, that the surface biofunctionalization improves peri-implant bone formation and remodeling, leading to an increased bone-to implant contact. However, within the limitations of the study set-up no benefit in the early phase of

  3. Differences in the incidence of apoptosis between in vivo and in vitro produced blastocysts of farm animal species: a comparative study

    NARCIS (Netherlands)

    Rubio Pomar, F.J.; Teerds, K.J.; Kidson, A.; Colenbrander, B.; Tharasanit, T.; Aguilar, B.; Roelen, B.A.J.

    2005-01-01

    The occurrence of pregnancies and births after embryo transfer (ET) of in vivo produced embryos is generally more successful compared to that of embryos produced in vitro. This difference in ET success has been observed when embryos of morphological equal (high) quality were used. The incidence of

  4. In vivo mapping of temporospatial changes in glucose utilization in rat brain during epileptogenesis: an 18F-fluorodeoxyglucose-small animal positron emission tomography study.

    Science.gov (United States)

    Guo, Y; Gao, F; Wang, S; Ding, Y; Zhang, H; Wang, J; Ding, M-P

    2009-09-15

    Cerebral glucose hypometabolism is common in temporal lobe epilepsy (TLE). The temporospatial evolution of these metabolic changes during epileptogenesis remains to be determined. We measured the regional normalized cerebral metabolic rate for glucose (nCMRglc) with (18)F-fluorodeoxyglucose (FDG)-small animal positron emission tomography (microPET) in animals receiving systemic pilocarpine application. The microPET scan was performed on day 2 (early), day 7 (latent) and 42 days (chronic phase) after the initial status epilepticus. We found specific temporospatial changes in glucose utilization in rats during the course of epileptogenesis. In the early phase, the limbic structures underwent the largest decrease in glucose utilization. Most brain structures were still hypometabolic in the latent phase and recovered in the chronic phase. Conversely, the hippocampus and thalamus presented with persistent hypometabolism during epileptogenesis. The cerebellum and pons maintained normal glucose utilization during this process. We also found that severe glucose hypometabolism in the entorhinal cortex during the early phase was correlated with epileptogenesis, indicating the critical role of the entorhinal cortex in the early stages of TLE.

  5. Is the use of plants in Jordanian folk medicine for the treatment of male sexual dysfunction scientifically based? Review of in vitro and in vivo human and animal studies.

    Science.gov (United States)

    Abbas, M A

    2017-04-01

    Male sexual dysfunction is a serious problem which has an impact on the quality of life. In Jordanian folk medicine, 56 plant species were reported to be used by males to improve sexual potency and as aphrodisiacs. The aim of this study was to search for scientific evidence justifying their folk use. Of the 15 studied plants, only five were found to enhance spermatogenesis. The other 10 were reported to decrease spermatogenesis at least by one study. The majority of the studied plants possessed a protective effect on testis in different in vivo models as well as antioxidant activities. The effect of these plants on steroidogenesis and the hypothalamic-gonadal axis was also reviewed. The effect of only five plants was studied on sexual behaviour enhancement and three of them were active. Three of the four studied plants enhanced erection. The mechanism of action of active constituents isolated from the studied plants was also investigated. In conclusion, many plants used in Jordanian folk medicine decreased or had no effect on spermatogenesis in animal models. These plants have antioxidant and/or adaptogenic effects, and this may result in a beneficial action on male reproductive system. © 2016 Blackwell Verlag GmbH.

  6. Remote in vivo stress assessment of aquatic animals with microencapsulated biomarkers for environmental monitoring

    Science.gov (United States)

    Gurkov, Anton; Shchapova, Ekaterina; Bedulina, Daria; Baduev, Boris; Borvinskaya, Ekaterina; Meglinski, Igor; Timofeyev, Maxim

    2016-11-01

    Remote in vivo scanning of physiological parameters is a major trend in the development of new tools for the fields of medicine and animal physiology. For this purpose, a variety of implantable optical micro- and nanosensors have been designed for potential medical applications. At the same time, the important area of environmental sciences has been neglected in the development of techniques for remote physiological measurements. In the field of environmental monitoring and related research, there is a constant demand for new effective and quick techniques for the stress assessment of aquatic animals, and the development of proper methods for remote physiological measurements in vivo may significantly increase the precision and throughput of analyses in this field. In the present study, we apply pH-sensitive microencapsulated biomarkers to remotely monitor the pH of haemolymph in vivo in endemic amphipods from Lake Baikal, and we compare the suitability of this technique for stress assessment with that of common biochemical methods. For the first time, we demonstrate the possibility of remotely detecting a change in a physiological parameter in an aquatic organism under ecologically relevant stressful conditions and show the applicability of techniques using microencapsulated biomarkers for remote physiological measurements in environmental monitoring.

  7. An in vivo animal study assessing long-term changes in hypothalamic cytokines following perinatal exposure to a chemical mixture based on Arctic maternal body burden

    Directory of Open Access Journals (Sweden)

    Li Nanqin

    2011-07-01

    Full Text Available Abstract Background The geographic distribution of environmental toxins is generally not uniform, with certain northern regions showing a particularly high concentration of pesticides, heavy metals and persistent organic pollutants. For instance, Northern Canadians are exposed to high levels of persistent organic pollutants like polychlorinated biphenyls (PCB, organochlorine pesticides (OCs and methylmercury (MeHg, primarily through country foods. Previous studies have reported associations between neuronal pathology and exposure to such toxins. The present investigation assessed whether perinatal exposure (gestation and lactation of rats to a chemical mixture (27 constituents comprised of PCBs, OCs and MeHg based on Arctic maternal exposure profiles at concentrations near human exposure levels, would affect brain levels of several inflammatory cytokines Methods Rats were dosed during gestation and lactation and cytokine levels were measured in the brains of offspring at five months of age. Hypothalamic cytokine protein levels were measured with a suspension-based array system and differences were determined using ANOVA and post hoc statistical tests. Results The early life PCB treatment alone significantly elevated hypothalamic interleukin-6 (IL-6 levels in rats at five months of age to a degree comparable to that of the entire chemical mixture. Similarly, the full mixture (and to a lesser degree PCBs alone elevated levels of the pro-inflammatory cytokine, IL-1b, as well as the anti-inflammatory cytokine, IL-10. The full mixture of chemicals also moderately increased (in an additive fashion hypothalamic levels of the pro-inflammatory cytokines, IL-12 and tumor necrosis factor (TNF-α. Challenge with bacterial endotoxin at adulthood generally increased hypothalamic levels to such a degree that differences between the perinatally treated chemical groups were no longer detectable. Conclusions These data suggest that exposure at critical

  8. In Vivo Bioluminescent Imaging (BLI: Noninvasive Visualization and Interrogation of Biological Processes in Living Animals

    Directory of Open Access Journals (Sweden)

    Steven Ripp

    2010-12-01

    Full Text Available In vivo bioluminescent imaging (BLI is increasingly being utilized as a method for modern biological research. This process, which involves the noninvasive interrogation of living animals using light emitted from luciferase-expressing bioreporter cells, has been applied to study a wide range of biomolecular functions such as gene function, drug discovery and development, cellular trafficking, protein-protein interactions, and especially tumorigenesis, cancer treatment, and disease progression. This article will review the various bioreporter/biosensor integrations of BLI and discuss how BLI is being applied towards a new visual understanding of biological processes within the living organism.

  9. In Vivo Bioluminescent Imaging (BLI): Noninvasive Visualization and Interrogation of Biological Processes in Living Animals

    Science.gov (United States)

    Close, Dan M.; Xu, Tingting; Sayler, Gary S.; Ripp, Steven

    2011-01-01

    In vivo bioluminescent imaging (BLI) is increasingly being utilized as a method for modern biological research. This process, which involves the noninvasive interrogation of living animals using light emitted from luciferase-expressing bioreporter cells, has been applied to study a wide range of biomolecular functions such as gene function, drug discovery and development, cellular trafficking, protein-protein interactions, and especially tumorigenesis, cancer treatment, and disease progression. This article will review the various bioreporter/biosensor integrations of BLI and discuss how BLI is being applied towards a new visual understanding of biological processes within the living organism. PMID:22346573

  10. In vivo ¹⁸F-FDG tumour uptake measurements in small animals using Cerenkov radiation.

    Science.gov (United States)

    Boschi, Federico; Calderan, Laura; D'Ambrosio, Daniela; Marengo, Mario; Fenzi, Alberto; Calandrino, Riccardo; Sbarbati, Andrea; Spinelli, Antonello E

    2011-01-01

    2-[(18)F]Fluoro-2-deoxy-D-glucose ((18)F-FDG) is a widely used PET radiotracer for the in vivo diagnosis of several diseases such as tumours. The positrons emitted by (18)F-FDG, travelling into tissues faster than the speed of light in the same medium, are responsible for Cerenkov radiation (CR) emission which is prevalently in the visible range. The purpose of this study is to show that CR escaping from tumour tissues of small living animals injected with (18)F-FDG can be detected with optical imaging (OI) techniques using a commercial optical instrument equipped with charge-coupled detectors (CCD). The theory behind the Cerenkov light emission and the source depth measurements using CR is first presented. Mice injected with (18)F-FDG or saline solution underwent dynamic OI acquisition and a comparison between images was performed. Multispectral analysis of the radiation was used to estimate the depth of the source of Cerenkov light. Small animal PET images were also acquired in order to compare the (18)F-FDG bio-distribution measured using OI and PET scanner. Cerenkov in vivo whole-body images of tumour-bearing mice and the measurements of the emission spectrum (560-660 nm range) are presented. Brain, kidneys and tumour were identified as a source of visible light in the animal body: the tissue time-activity curves reflected the physiological accumulation of (18)F-FDG in these organs. The identification is confirmed by the comparison between CR and (18)F-FDG images. These results will allow the use of conventional OI devices for the in vivo study of glucose metabolism in cancer and the assessment, for example, of anti-cancer drugs. Moreover, this demonstrates that (18)F-FDG can be employed as it is a bimodal tracer for PET and OI techniques.

  11. In vivo {sup 18}F-FDG tumour uptake measurements in small animals using Cerenkov radiation

    Energy Technology Data Exchange (ETDEWEB)

    Boschi, Federico; Calderan, Laura; Fenzi, Alberto; Sbarbati, Andrea [University of Verona, Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, Verona (Italy); D' Ambrosio, Daniela; Marengo, Mario [S. Orsola - Malpighi University Hospital, Medical Physics Department, Bologna (Italy); Calandrino, Riccardo; E Spinelli, Antonello [S. Raffaele Scientific Institute, Medical Physics Department, Milan (Italy)

    2011-01-15

    2-[{sup 18}F]Fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) is a widely used PET radiotracer for the in vivo diagnosis of several diseases such as tumours. The positrons emitted by {sup 18}F-FDG, travelling into tissues faster than the speed of light in the same medium, are responsible for Cerenkov radiation (CR) emission which is prevalently in the visible range. The purpose of this study is to show that CR escaping from tumour tissues of small living animals injected with {sup 18}F-FDG can be detected with optical imaging (OI) techniques using a commercial optical instrument equipped with charge-coupled detectors (CCD). The theory behind the Cerenkov light emission and the source depth measurements using CR is first presented. Mice injected with {sup 18}F-FDG or saline solution underwent dynamic OI acquisition and a comparison between images was performed. Multispectral analysis of the radiation was used to estimate the depth of the source of Cerenkov light. Small animal PET images were also acquired in order to compare the {sup 18}F-FDG bio-distribution measured using OI and PET scanner. Cerenkov in vivo whole-body images of tumour-bearing mice and the measurements of the emission spectrum (560-660 nm range) are presented. Brain, kidneys and tumour were identified as a source of visible light in the animal body: the tissue time-activity curves reflected the physiological accumulation of {sup 18}F-FDG in these organs. The identification is confirmed by the comparison between CR and {sup 18}F-FDG images. These results will allow the use of conventional OI devices for the in vivo study of glucose metabolism in cancer and the assessment, for example, of anti-cancer drugs. Moreover, this demonstrates that {sup 18}F-FDG can be employed as it is a bimodal tracer for PET and OI techniques. (orig.)

  12. In vivo measurement of hippocampal GABAA/cBZR density with [18F]-flumazenil PET for the study of disease progression in an animal model of temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Lucy Vivash

    Full Text Available PURPOSE: Imbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE. This study aimed to investigate whether [(18F]-flumazenil ([(18F]-FMZ PET could be used to non-invasively characterise GABAA/central benzodiazepine receptor (GABAA/cBZR density and affinity in vivo in the post-kainic acid status epilepticus (SE model of TLE. METHODS: Dynamic [(18F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM. SE was induced in eight male Wistar rats (10 weeks of age by i.p. injection of kainic acid (7.5-25 mg/kg, while control rats (n = 7 received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [(18F]-FMZ PET scan (3.6-4.6 nmol. The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [(18F]-FMZ PET data. KEY FINDINGS: The PSM was found to adequately model [(18F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01, accompanied by an increase in apparent affinity (p<0.05 compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05, but did not correlate with [(18F]-FMZ binding. SIGNIFICANCE: Alterations to hippocampal GABAA/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [(18F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [(18F]-FMZ PET is useful for investigating the role that changes GABAA/cBZR density and binding affinity play in the pathogenesis of TLE.

  13. Training of different endoscopic skills on ex-vivo animal model.

    Science.gov (United States)

    Martinek, Jan; Stefanova, Magdalena; Suchanek, Stepan; Zavada, Filip; Svobodova, Barbora; Strosova, Alice; Zavoral, Miroslav

    2014-04-01

    Virtual reality simulator and ex vivo animal models are used for training of both basic and advanced endoscopic techniques. The aim of this study was to assess whether hands-on training on ex vivo animal model improves endoscopic skills. Four different endoscopic techniques were practiced: endoscopic resection, endoscopic stenting, application of the over-the-scope (OVESCO) clip, and endoscopic submucosal dissection (ESD). Except for 2 participants, all trainees participated in a 1-day course. Two remaining participants took part in 7 ESD courses. All training courses consisted of theoretical introduction and a 6-hour training on Erlangen Active Training Simulator. The endoscopic skills were assessed before and after the training session by 2 independent assessors. Each assessor evaluated the skills by using a score on a scale of 1 to 5, where 1 stands for excellent and 5 for insufficient. Each assessor also assessed whether the procedure was successfully completed. The main outcome measurement was the percentage of participants who successfully completed the procedure during the test. For endoscopic resection, endoscopists (n = 15) improved their skills (median [10th and 90th percentiles] score before training, 3.5 [2.7-4.2]; after training 1.5 [1-2.3], P skills to prepare and apply the clip (given the score of 4.5 [3.9-5] before and 2.0 [1.2-2.8] after, P skills (with scores of 4 before and 1.6 after); given the small number of participants, this finding is statistically insignificant. The effect of training on clinical outcome was not investigated. There was a lack of pretraining versus posttraining tests blinding. A 1-day training course on ex vivo animal model improves general endoscopic competence on simulator in endoscopic resection, insertion of stents, and application of OVESCO clips. In contrast, 1-day course does not improve skills for ESD that requires a higher number of training courses.

  14. New quantitative and multi-modal approach for in-vivo studies of small animals: coupling of the {beta}-microprobe with magnetic techniques and development of voxelized rat and mouse phantoms; Nouvelle approche multimodale et quantitative pour les etudes in vivo chez le petit animal: couplage de la {beta}-MicroProbe aux techniques magnetiques et developpement de fantomes de rat et de souris voxelises

    Energy Technology Data Exchange (ETDEWEB)

    Desbree, A

    2005-09-15

    For the last 15 years, animal models that mimic human disorders have become ubiquitous participants to understand biological mechanisms and human disorders and to evaluate new therapeutic approaches. The necessity to study these models in the course of time has stimulated the development of instruments dedicated to in vivo small animal studies. To further understand physiopathological processes, the current challenge is to couple simultaneously several of these methods. Given this context, the combination of the magnetic and radioactive techniques remains an exciting challenge since it is still limited by strict technical constraints. Therefore we propose to couple the magnetic techniques with the radiosensitive Beta-Microprobe, developed in the IPB group and which shown to be an elegant alternative to PET measurements. In this context, the thesis was dedicated to the study of the coupling feasibility from a physical point of view, by simulation and experimental characterizations. Then, the determination of a biological protocol was carried out on the basis of pharmacokinetic studies. The experiments have shown the possibility to use the probe for radioactive measurements under intense magnetic field simultaneously to anatomical images acquisitions. Simultaneously, we have sought to improve the quantification of the radioactive signal using a voxelized phantom of a rat brain. Finally, the emergence of transgenic models led us to reproduce pharmacokinetic studies for the mouse and to develop voxelized mouse phantoms. (author)

  15. Establishment of Larval Zebrafish as an Animal Model to Investigate Trypanosoma cruzi Motility In Vivo.

    Science.gov (United States)

    Akle, Veronica; Agudelo-Dueñas, Nathalie; Molina-Rodriguez, Maria A; Kartchner, Laurel Brianne; Ruth, Annette Marie; González, John M; Forero-Shelton, Manu

    2017-09-30

    Chagas disease is a parasitic infection caused by Trypanosoma cruzi, whose motility is not only important for localization, but also for cellular binding and invasion. Current animal models for the study of T. cruzi allow limited observation of parasites in vivo, representing a challenge for understanding parasite behavior during the initial stages of infection in humans. This protozoan has a flagellar stage in both vector and mammalian hosts, but there are no studies describing its motility in vivo.The objective of this project was to establish a live vertebrate zebrafish model to evaluate T. cruzi motility in the vascular system. Transparent zebrafish larvae were injected with fluorescently labeled trypomastigotes and observed using light sheet fluorescence microscopy (LSFM), a noninvasive method to visualize live organisms with high optical resolution. The parasites could be visualized for extended periods of time due to this technique's relatively low risk of photodamage compared to confocal or epifluorescence microscopy. T. cruzi parasites were observed traveling in the circulatory system of live zebrafish in different-sized blood vessels and the yolk. They could also be seen attached to the yolk sac wall and to the atrioventricular valve despite the strong forces associated with heart contractions. LSFM of T. cruzi-inoculated zebrafish larvae is a valuable method that can be used to visualize circulating parasites and evaluate their tropism, migration patterns, and motility in the dynamic environment of the cardiovascular system of a live animal.

  16. Considerations for Infectious Disease Research Studies Using Animals

    Science.gov (United States)

    Colby, Lesley A; Quenee, Lauriane E; Zitzow, Lois A

    2017-01-01

    Animal models are vital in understanding the transmission and pathogenesis of infectious organisms and the host immune response to infection. In addition, animal models are essential in vaccine and therapeutic drug development and testing. Prior to selecting an animal model to use when studying an infectious agent, the scientific team must determine that sufficient in vitro and ex vivo data are available to justify performing research in an animal model, that ethical considerations are addressed, and that the data generated from animal work will add useful information to the body of scientific knowledge. Once it is established that an animal should be used, the questions become ‘Which animal model is most suitable?’ and ‘Which experimental design issues should be considered?’ The answers to these questions take into account numerous factors, including scientific, practical, welfare, and regulatory considerations, which are the focus of this article. PMID:28662751

  17. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Olivia Perwitasari

    Full Text Available Influenza A virus (IAV causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

  18. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

    Science.gov (United States)

    Perwitasari, Olivia; Johnson, Scott; Yan, Xiuzhen; Register, Emery; Crabtree, Jackelyn; Gabbard, Jon; Howerth, Elizabeth; Shacham, Sharon; Carlson, Robert; Tamir, Sharon; Tripp, Ralph A

    2016-01-01

    Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

  19. In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans.

    Science.gov (United States)

    Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R; Öz, Gülin

    2015-02-01

    Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of (13)C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the (13)C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness.

  20. In vitro and in vivo animal model antitrypanosomal evaluation of ten ...

    African Journals Online (AJOL)

    In vitro and in vivo animal model antitrypanosomal evaluation of ten medicinal plant extracts from south west Nigeria. ... analysis, only the T. superba root bark extract totally inhibited the growth of parasites in both rats and mice; all the other root bark extracts resulted in parasite clearance in rats only. The duration of

  1. In vivo imaging of dopamine transporter function in rat striatum using pinhole SPECT and 123I-beta-CIT coregistered with small animal MRI

    CERN Document Server

    Dierkes, K

    2001-01-01

    The aim of this study was to establish in vivo imaging of dopamine transporter function in a small animal model of Parkinson's disease using pinhole SPECT and 123I labeled beta-CIT. Since functional imaging of small animals can hardly be interpreted without localization to related anatomical structures, MRI-SPECT coregistration secondly was established as an inexpensive tool for in vivo monitoring of physiological and pathological alterations in striatal dopamine transporters using beta-CIT as an specific radionuclear ligand.

  2. Function of dopamine transporter is compromised in DYT1 transgenic animal model in vivo.

    Science.gov (United States)

    Hewett, Jeff; Johanson, Peter; Sharma, Nutan; Standaert, David; Balcioglu, Aygul

    2010-04-01

    Early onset torsion dystonia (DYT1), the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein, torsinA. We previously examined the effect of the human mutant torsinA on striatal dopaminergic function in a conventional transgenic mouse model of DYT1 dystonia (hMT1), in which human mutant torsinA is expressed under the cytomegalovirus promotor. Systemic administration of amphetamine did not increase dopamine (DA) release as efficiently in these mice as compared with wild-type transgenic and non-transgenic mice. We, now, studied the contribution of the DA transporter (DAT) to amphetamine-induced DA release in hMT1 transgenic mice using in vivo no-net flux microdialysis. This method applies different concentrations of DA through the microdialysis probe and measures DA concentration at the output of the probe following an equilibrium period. The slope (extraction fraction) is the measure of the DAT activity in vivo. The slope for hMT1 transgenic mice was 0.58 +/- 0.07 and for non-transgenic animals, 0.87 +/- 0.06 (p beam task. These data implies that altered DAT function may contribute to impaired DA neurotransmission and clinical symptoms in human DYT1 dystonia.

  3. [Construction and improvement of animal models with different positional osseous metastasis of prostate cancer in vivo].

    Science.gov (United States)

    Bi, Y X; Xiao, M H; Zhang, N N; Li, X Y; Mao, X P; Zhang, K; Zhang, Z R; Zhao, L Y

    2017-08-18

    To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo. Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively. The change of mouse activity, tumor formation, tumor size and survival time were observed respectively. And the femur tissue and spinal tissue were obtained from the mice after death. The gray value of iconography were measured by imageological examination of femur tissue, and the final histopathological examination were taken to determine the tumor type in both femur and spinal tissue. The tumor growth could be touched at the puncture site in all the mice after inoculated for 7 days. There were no obvious differences in the time of tumorigenesis, the rate of tumor growth and tumor size among the mice in the same group (P>0.05). As the result, the construction femoral bone and lumbar vertebra metastatic models of PCa had been confirmed by iconography and pathology detection. At the same time, the survival time of the mice inoculated with low concentrations of PCa cells was obviously longer than that of high concentrations of PCa cells ( at least 2 weeks longer). The animal models with different positional osseous metastasis (limbs and axial skeleton) of PCa using the same PCa cells (RM-1) had been first constructed successfully in our study. At the same time, a high success rate of construction of PCa animal model with bone metastasis was obtained by femoral bone marrow cavity injection of PCa cells. The rate of tumor growth was rapid, animal survival time was appropriate, and the PCa animal

  4. Error rates in bite mark analysis in an in vivo animal model.

    Science.gov (United States)

    Avon, S L; Victor, C; Mayhall, J T; Wood, R E

    2010-09-10

    Recent judicial decisions have specified that one foundation of reliability of comparative forensic disciplines is description of both scientific approach used and calculation of error rates in determining the reliability of an expert opinion. Thirty volunteers were recruited for the analysis of dermal bite marks made using a previously established in vivo porcine-skin model. Ten participants were recruited from three separate groups: dentists with no experience in forensics, dentists with an interest in forensic odontology, and board-certified diplomates of the American Board of Forensic Odontology (ABFO). Examiner demographics and measures of experience in bite mark analysis were collected for each volunteer. Each participant received 18 completely documented, simulated in vivo porcine bite mark cases and three paired sets of human dental models. The paired maxillary and mandibular models were identified as suspect A, suspect B, and suspect C. Examiners were tasked to determine, using an analytic method of their own choosing, whether each bite mark of the 18 bite mark cases provided was attributable to any of the suspect dentitions provided. Their findings were recorded on a standardized recording form. The results of the study demonstrated that the group of inexperienced examiners often performed as well as the board-certified group, and both inexperienced and board-certified groups performed better than those with an interest in forensic odontology that had not yet received board certification. Incorrect suspect attributions (possible false inculpation) were most common among this intermediate group. Error rates were calculated for each of the three observer groups for each of the three suspect dentitions. This study demonstrates that error rates can be calculated using an animal model for human dermal bite marks, and although clinical experience is useful, other factors may be responsible for accuracy in bite mark analysis. Further, this study demonstrates

  5. Selected recent in vivo studies on chemical measurements in invertebrates.

    Science.gov (United States)

    Majdi, S; Ren, L; Fathali, H; Li, X; Ewing, A G

    2015-06-07

    In vivo measurements of neurotransmitters and related compounds have provided a better understanding of the chemical interactions that are a major part in functioning of brains. In addition, a great deal of technology has been developed to measure chemical species in other areas of living organisms. A key part of this work has been sampling technologies as well as direct measurements in vivo. This is extremely important when sampling from the smallest animal systems. Yet, very small invertebrate systems are excellent models and often have better defined and more easily manipulated genetics. This review focuses on in vivo measurements, electrochemical methods, fluorescence techniques, and sampling and is further narrowed to work over approximately the last three years. Rapid developments of in vivo studies in these model systems should aid in finding solutions to biological and bioanalytical challenges related to human physiological functions and neurodegenerative diseases.

  6. Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.

    Science.gov (United States)

    Zhu, Hong; Kochevar, Irene E; Behlau, Irmgard; Zhao, Jie; Wang, Fenghua; Wang, Yucheng; Sun, Xiaodong; Hamblin, Michael R; Dai, Tianhong

    2017-01-01

    To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

  7. The study of animal metacognition.

    Science.gov (United States)

    Smith, J David

    2009-09-01

    Do nonhuman animals share humans' capacity for metacognition--that is, for monitoring or regulating their own cognitive states? Comparative psychologists have approached this question by testing a dolphin, pigeons, rats, monkeys and apes using perception, memory and food-concealment paradigms. There is growing evidence that animals share functional parallels with humans' conscious metacognition, although the field has not confirmed full experiential parallels and this remains an open question. This article reviews this new area of comparative inquiry and describes significant empirical milestones, remaining theoretical milestones and the prospects for continuing progress in a rapidly developing area. This research area opens a new window on reflective mind in animals, illuminating its phylogenetic emergence and allowing researchers to trace the antecedents of human consciousness.

  8. Evalution of oxidative stress in diabetic animals by in vivo electron spin resonance measurement--role of protein kinase C.

    Science.gov (United States)

    Sonta, Toshiyo; Inoguchi, Toyoshi; Tsubouchi, Hirotaka; Sekiguchi, Naotaka; Kobayashi, Kunihisa; Matsumoto, Shingo; Utsumi, Hideo; Nawata, Hajime

    2004-12-01

    Enhanced oxidative stress may be an important contributor to the pathogenesis of diabetic vascular complication. Although hyperglycemia-induced oxidative stress in diabetes has been well documented, exact source in vivo remains to be elucidated. Here we report a role of protein kinase C (PKC) in oxidative stress in diabetic animals using a technique of in vivo electron spin resonance (ESR) measurement that has been developed for direct and non-invasive analysis of free radical generation in living animals. First, using this measurement, we confirmed that streptozotocin-induced diabetic rats which showed a significant increase in free radical generation, which was restored by alpha-tocopherol treatment. Treatment of PKC inhibitor CGP41251 (50 mg/kg) or NAD(P)H oxidase inhibitor apocynin (5 mg/kg) restored the increased free radical generation in those diabetic animals. In conclusion, the present study provided the evidence that PKC-dependent activation of vascular NAD(P)H oxidase may be a major source in enhanced oxidative stress in diabetes in vivo. This may contribute to the pathogenesis of diabetic vascular complications.

  9. Comparative assessment of fluorescent proteins for in vivo imaging in an animal model system.

    Science.gov (United States)

    Heppert, Jennifer K; Dickinson, Daniel J; Pani, Ariel M; Higgins, Christopher D; Steward, Annette; Ahringer, Julie; Kuhn, Jeffrey R; Goldstein, Bob

    2016-11-07

    Fluorescent protein tags are fundamental tools used to visualize gene products and analyze their dynamics in vivo. Recent advances in genome editing have expedited the precise insertion of fluorescent protein tags into the genomes of diverse organisms. These advances expand the potential of in vivo imaging experiments and facilitate experimentation with new, bright, photostable fluorescent proteins. Most quantitative comparisons of the brightness and photostability of different fluorescent proteins have been made in vitro, removed from biological variables that govern their performance in cells or organisms. To address the gap, we quantitatively assessed fluorescent protein properties in vivo in an animal model system. We generated transgenic Caenorhabditis elegans strains expressing green, yellow, or red fluorescent proteins in embryos and imaged embryos expressing different fluorescent proteins under the same conditions for direct comparison. We found that mNeonGreen was not as bright in vivo as predicted based on in vitro data but is a better tag than GFP for specific kinds of experiments, and we report on optimal red fluorescent proteins. These results identify ideal fluorescent proteins for imaging in vivo in C. elegans embryos and suggest good candidate fluorescent proteins to test in other animal model systems for in vivo imaging experiments. © 2016 Heppert et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. Multiplane spectroscopic whole-body photoacoustic imaging of small animals in vivo.

    Science.gov (United States)

    Jeon, Mansik; Kim, Jeesu; Kim, Chulhong

    2016-03-01

    We have successfully developed a multiscale acoustic-resolution photoacoustic tomography system in a single imaging platform. By switching between ultrasound transducers (center frequencies 5 and 40 MHz) and optical condensers, we have photoacoustically imaged microvasculatures of small animals in vivo at different scales. Further, we have extended the field of view of our imaging system to entire bodies of small animals. At different imaging planes, we have noninvasively imaged the major blood vessels (e.g., descending aorta, intercostal vessels, cephalic vessels, brachial vessels, femoral vessels, popliteal vessels, lateral marginal vessels, cranial mesenteric vessels, mammalian vessels, carotid artery, jugular vein, subclavian vessels, iliac vessels, and caudal vessels) as well as intact internal organs (e.g., spleen, liver, kidney, intestine, cecum, and spinal cord) of the animals in vivo. The spectroscopic whole-body photoacoustic imaging clearly reveals the spectral responses of the internal structures. Similar to other existing preclinical whole-body imaging systems, this whole-body photoacoustic tomography can be a useful tool for small-animal research.

  11. In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis.

    Science.gov (United States)

    Gutowski, Michal B; Wilson, Leslie; Van Gelder, Russell N; Pepple, Kathryn L

    2017-03-01

    We develop a quantitative bioluminescence assay for in vivo longitudinal monitoring of inflammation in animal models of uveitis. Three models of experimental uveitis were induced in C57BL/6 albino mice: primed mycobacterial uveitis (PMU), endotoxin-induced uveitis (EIU), and experimental autoimmune uveitis (EAU). Intraperitoneal injection of luminol sodium salt, which emits light when oxidized, provided the bioluminescence substrate. Bioluminescence images were captured by a PerkinElmer In Vivo Imaging System (IVIS) Spectrum and total bioluminescence was analyzed using Living Image software. Bioluminescence on day zero was compared to bioluminescence on the day of peak inflammation for each model. Longitudinal bioluminescence imaging was performed in EIU and EAU. In the presence of luminol, intraocular inflammation generates detectable bioluminescence in three mouse models of uveitis. Peak bioluminescence in inflamed PMU eyes (1.46 × 105 photons/second [p/s]) was significantly increased over baseline (1.47 × 104 p/s, P = 0.01). Peak bioluminescence in inflamed EIU eyes (3.18 × 104 p/s) also was significantly increased over baseline (1.09 × 104 p/s, P = 0.04), and returned to near baseline levels by 48 hours. In EAU, there was a nonsignificant increase in bioluminescence at peak inflammation. In vivo bioluminescence may be used as a noninvasive, quantitative measure of intraocular inflammation in animal models of uveitis. Primed mycobacterial uveitis and EIU are both acute models with robust anterior inflammation and demonstrated significant changes in bioluminescence corresponding with peak inflammation. Experimental autoimmune uveitis is a more indolent posterior uveitis and generated a more modest bioluminescent signal. In vivo imaging system bioluminescence is a nonlethal, quantifiable assay that can be used for monitoring inflammation in animal models of uveitis.

  12. The Pleurodele, an animal model for space biology studies

    Science.gov (United States)

    Gualandris, L.; Grinfeld, S.; Foulquier, F.; Kan, P.; Duprat, A. M.

    Pleurodeles waltl, an Urodele amphibian is proposed as a model for space biology studies. Our laboratory is developing three types of experiments in space using this animal: 1) in vivo fertilization and development (``FERTILE'' project); 2) influence of microgravity and space radiation on the organization and preservation of spacialized structures in the neurons and muscle cells (in vitro; ``CELIMENE'' PROJECT); 3) influence of microgravity on tissue regeneration (muscle, bone, epidermis and spinal cord).

  13. Microscopy of bacterial translocation during small bowel obstruction and ischemia in vivo – a new animal model

    Directory of Open Access Journals (Sweden)

    Hafner Mathias

    2002-08-01

    Full Text Available Abstract Background Existing animal models provide only indirect information about the pathogenesis of infections caused by indigenous gastrointestinal microflora and the kinetics of bacterial translocation. The aim of this study was to develop a novel animal model to assess bacterial translocation and intestinal barrier function in vivo. Methods In anaesthetized male Wistar rats, 0.5 ml of a suspension of green fluorescent protein-transfected E. coli was administered by intraluminal injection in a model of small bowel obstruction. Animals were randomly subjected to non-ischemic or ischemic bowel obstruction. Ischemia was induced by selective clamping of the terminal mesenteric vessels feeding the obstructed bowel loop. Time intervals necessary for translocation of E. coli into the submucosal stroma and the muscularis propria was assessed using intravital microscopy. Results Bacterial translocation into the submucosa and muscularis propria took a mean of 36 ± 8 min and 80 ± 10 min, respectively, in small bowel obstruction. Intestinal ischemia significantly accelerated bacterial translocation into the submucosa (11 ± 5 min, p E. coli were visible in frozen sections of small bowel, mesentery, liver and spleen taken two hours after E. coli administration. Conclusions Intravital microscopy of fluorescent bacteria is a novel approach to study bacterial translocation in vivo. We have applied this technique to define minimal bacterial transit time as a functional parameter of intestinal barrier function.

  14. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates.

    Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity.

    Although chimpanzees are the only animals fully permissive for HBV infection, their use for research purpose is severely limited by the high costs and strong ethical constrains. The only alternative source of HBV-permissive hepatocytes is the Asian tree shrew Tupaia belangeri. Though experimental infection of these squirrel-like mammals, phylogenetically related to primates, results only in a mild, transient replication, primary hepatocytes isolated from T. belangeri turned out to be a reliable tool for in vitro HBV infection experiments.

    Along with invaluable infection studies in chimpanzees, avian and mammalian HBV-related viruses continue to offer ample opportunities for studies in naturally occurring hosts. In general, most of our progresses in hepatitis B virus research are based on infection studies with two HBV-related animal viruses: the woodchuck HBV (WHV, which infects the Eastern American woodchuck (Marmota monax, and the duck HBV (DHBV, which infects Peking ducks. Both animal models have been essential for understanding various steps of viral life-cycle and factors involved in establishment of virus

  15. Significance of different animal species in experimental models for in vivo investigations of hematopoiesis

    Directory of Open Access Journals (Sweden)

    Kovačević-Filipović Milica

    2004-01-01

    Full Text Available Numerous discoveries in medicine are results of experiments on different animal species. The most frequently used animals in hematopoiesis investigations are laboratory mice and rats, but so-called big animals, such as pigs, sheep, cats, dogs, and monkeys, evolution-wise closer to humans have a place in experimental hematology as well. The specific problematics of a certain animal specie can lead to fundamental knowledge on certain aspects of the process of hematopoiesis end the biology of stem cells in hematopoiesis. Furthermore, comparative investigations of certain phenomena in different species help in the recognition of the general rules in the living world. In the area f preclinicalinvesti- gations, animal models are an inevitable step in studies of transplantation biology of stem cells in hematopoiesis, as well as in studies of biologically active molecules which have an effect on the hematopoietic system. Knowledge acquired on animal models is applied in both human and veterinary medicine.

  16. Epigenetic Case Studies in Agricultural Animals

    Science.gov (United States)

    In many biological processes, the regulation of gene expression involves epigenetic mechanisms. An altered pattern of epigenetic modification is central to many animal diseases. Using animal disease models, we have studied one of the major epigenetic components: DNA methylation. We characterized the...

  17. A Comparison of Red Fluorescent Proteins to Model DNA Vaccine Expression by Whole Animal In Vivo Imaging.

    Science.gov (United States)

    Kinnear, Ekaterina; Caproni, Lisa J; Tregoning, John S

    2015-01-01

    DNA vaccines can be manufactured cheaply, easily and rapidly and have performed well in pre-clinical animal studies. However, clinical trials have so far been disappointing, failing to evoke a strong immune response, possibly due to poor antigen expression. To improve antigen expression, improved technology to monitor DNA vaccine transfection efficiency is required. In the current study, we compared plasmid encoded tdTomato, mCherry, Katushka, tdKatushka2 and luciferase as reporter proteins for whole animal in vivo imaging. The intramuscular, subcutaneous and tattooing routes were compared and electroporation was used to enhance expression. We observed that overall, fluorescent proteins were not a good tool to assess expression from DNA plasmids, with a highly heterogeneous response between animals. Of the proteins used, intramuscular delivery of DNA encoding either tdTomato or luciferase gave the clearest signal, with some Katushka and tdKatushka2 signal observed. Subcutaneous delivery was weakly visible and nothing was observed following DNA tattooing. DNA encoding haemagglutinin was used to determine whether immune responses mirrored visible expression levels. A protective immune response against H1N1 influenza was induced by all routes, even after a single dose of DNA, though qualitative differences were observed, with tattooing leading to high antibody responses and subcutaneous DNA leading to high CD8 responses. We conclude that of the reporter proteins used, expression from DNA plasmids can best be assessed using tdTomato or luciferase. But, the disconnect between visible expression level and immunogenicity suggests that in vivo whole animal imaging of fluorescent proteins has limited utility for predicting DNA vaccine efficacy.

  18. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  19. Animal models for the study of tendinopathy.

    Science.gov (United States)

    Warden, S J

    2007-04-01

    Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.

  20. Ex-vivo and live animal models are equally effective training for the management of a penetrating cardiac injury.

    Science.gov (United States)

    Izawa, Yoshimitsu; Hishikawa, Shuji; Muronoi, Tomohiro; Yamashita, Keisuke; Maruyama, Hiroyuki; Suzukawa, Masayuki; Lefor, Alan Kawarai

    2016-01-01

    Live tissue models are considered the most useful simulation for training in the management for hemostasis of penetrating injuries. However, these models are expensive, with limited opportunities for repetitive training. Ex-vivo models using tissue and a fluid pump are less expensive, allow repetitive training and respect ethical principles in animal research. The purpose of this study is to objectively evaluate the effectiveness of ex-vivo training with a pump, compared to live animal model training. Staff surgeons and residents were divided into live tissue training and ex-vivo training groups. Training in the management of a penetrating cardiac injury was conducted for each group, separately. One week later, all participants were formally evaluated in the management of a penetrating cardiac injury in a live animal. There are no differences between the two groups regarding average years of experience or previous trauma surgery experience. All participants achieved hemostasis, with no difference between the two groups in the Global Rating Scale score (ex-vivo: 25.2 ± 6.3, live: 24.7 ± 6.3, p = 0.646), blood loss (1.6 ± 0.7, 2.0 ± 0.6, p = 0.051), checklist score (3.7 ± 0.6, 3.6 ± 0.9, p = 0.189), or time required for repair (101 s ± 31, 107 s ± 15, p = 0.163), except overall evaluation (3.8 ± 0.9, 3.4 ± 0.9, p = 0.037). The internal consistency reliability and inter-rater reliability in the Global Rating Scale were excellent (0.966 and 0.953 / 0.719 and 0.784, respectively), and for the checklist were moderate (0.570 and 0.636 / 0.651 and 0.607, respectively). The validity is rated good for both the Global Rating Scale (Residents: 21.7 ± 5.6, Staff: 28.9 ± 4.7, p = 0.000) and checklist (Residents: 3.4 ± 0.9, Staff Surgeons: 3.9 ± 0.3, p = 0.003). The results of self-assessment questionnaires were similarly high (4.2-4.9) with scores in self-efficacy increased after

  1. Bias During the Evaluation of Animal Studies?

    Directory of Open Access Journals (Sweden)

    Andrew Knight

    2012-02-01

    Full Text Available My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  2. Coagulation Management in Jersey Calves: An ex vivo Study.

    Science.gov (United States)

    Gröning, Sabine; Maas, Judith; van Geul, Svenja; Rossaint, Rolf; Steinseifer, Ulrich; Grottke, Oliver

    2017-01-01

    Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood. © 2017 S. Karger AG, Basel.

  3. Bias During the Evaluation of Animal Studies?

    Science.gov (United States)

    Knight, Andrew

    2012-01-01

    Simple Summary Animal experimentation evokes strong emotional responses in people on both sides of the debate surrounding its ethical status. However, the true level of its usefulness to society may only be discerned by careful examination of reliable scientific evidence. My recent book, The Costs and Benefits of Animal Experiments, reviewed more than 500 relevant scientific publications. Recently in this journal, however, a reviewer essentially accused me of bias. Yet the conclusions of my book are based on sound reasoning and strong evidence, and no critic has yet provided any substantive evidence to refute them. Abstract My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust. PMID:26486779

  4. In vivo response to polypropylene following implantation in animal models: a review of biocompatibility.

    Science.gov (United States)

    Kelly, Michelle; Macdougall, Katherine; Olabisi, Oluwafisayo; McGuire, Neil

    2017-02-01

    Polypropylene is a material that is commonly used to treat pelvic floor conditions such as pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Owing to the nature of complications experienced by some patients implanted with either incontinence or prolapse meshes, the biocompatibility of polypropylene has recently been questioned. This literature review considers the in vivo response to polypropylene following implantation in animal models. The specific areas explored in this review are material selection, impact of anatomical location, and the structure, weight and size of polypropylene mesh types. All relevant abstracts from original articles investigating the host response of mesh in vivo were reviewed. Papers were obtained and categorised into various mesh material types: polypropylene, polypropylene composites, and other synthetic and biologically derived mesh. Polypropylene mesh fared well in comparison with other material types in terms of host response. It was found that a lightweight, large-pore mesh is the most appropriate structure. The evidence reviewed shows that polypropylene evokes a less inflammatory or similar host response when compared with other materials used in mesh devices.

  5. The effect of radiofrequency ablation on different organs: Ex vivo and in vivo comparative studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Rhim, Hyunchul, E-mail: rhimhc@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Choi, Dongil; Kim, Young-sun; Lee, Min Woo; Chang, Ilsoo; Lee, Won Jae; Lim, Hyo K. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2011-11-15

    Objective: The purposes of this study are to evaluate the ex vivo and in vivo efficacy of radiofrequency ablation (RFA) on different porcine tissues by the ablation of three different sites simultaneously. Materials and methods: A multichannel RFA system, enables three separate tumors to be ablated simultaneously, was used. RFA procedures were applied to normal porcine liver, kidney, and muscle together ex vivo (n = 12) and in vivo (n = 17). Pre-impedances, defined as baseline systemic impedances of tissues before beginning RFA, and the areas of ablation zones were measured and compared. Results: The areas of ablation zones among three organs had a significant difference in decreasing order as follows: liver, muscle, and kidney in the ex vivo study (p = 0.001); muscle, liver, and kidney in the in vivo study (p < 0.0001). The areas of ablation zones between ex vivo and in vivo had a significant difference in the liver and muscle (each p < 0.05). There was no significant correlation between the areas of ablation zones and pre-impedances in both studies. Conclusions: Renal RFA produced the smallest ablation zone in both in vivo and ex vivo studies. Muscular RFA demonstrated the largest ablation zone in the in vivo study, and hepatic RFA showed the largest ablation zone in the ex vivo study. This variability in the tissues should be considered for performing an optimized RFA for each organ site.

  6. Biomedical applications of polyhydroxyalkanoates: an overview of animal testing and in vivo responses.

    Science.gov (United States)

    Valappil, Sabeel P; Misra, Superb K; Boccaccini, Aldo R; Roy, Ipsita

    2006-11-01

    Polyhydroxyalkanoates (PHAs) have been established as biodegradable polymers since the second half of the twentieth century. Altering monomer composition of PHAs allows the development of polymers with favorable mechanical properties, biocompatibility and desirable degradation rates, under specific physiological conditions. Hence, the medical applications of PHAs have been explored extensively in recent years. PHAs have been used to develop devices, including sutures, nerve repair devices, repair patches, slings, cardiovascular patches, orthopedic pins, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, bone-marrow scaffolds, tissue engineered cardiovascular devices and wound dressings. So far, various tests on animal models have shown polymers, from the PHA family, to be compatible with a range of tissues. Often, pyrogenic contaminants copurified with PHAs limit their pharmacological application rather than the monomeric composition of the PHAs and thus the purity of the PHA material is critical. This review summarizes the animal testing, tissue response, in vivo molecular stability and challenges of using PHAs for medical applications. In future, PHAs may become the materials of choice for various medical applications.

  7. A shift from cell cultures to creatures: in vivo imaging of small animals in experimental regenerative medicine.

    Science.gov (United States)

    Studwell, Anna J; Kotton, Darrell N

    2011-11-01

    Although the use of small animals for in vivo experimentation has been widespread, only recently has there been easy availability of techniques that allow noninvasive in vivo imaging of small animals. Because these techniques allow the same individual subject to be followed longitudinally throughout the duration of an experiment, their use is rapidly changing the way small animals are employed in the laboratory. In this review, we focus on six imaging modalities that are increasingly employed for small animal in vivo imaging: optical imaging (OI), magnetic resonance imaging (MRI), computed tomography (CT), single-photon emission tomography (SPECT), ultrasound (US), and positron-emission tomography (PET). Each modality allows for the noninvasive tracking of cells and cell products in vivo. In addition, multimodality imaging, combining two or more of these techniques, has also been increasingly employed to overcome the limitations of each independent technique. After reviewing these available imaging modalities, we detail their experimental application, exemplified by the emerging field of regenerative medicine, referring to publications whose conclusions would otherwise be difficult to support without the availability of in vivo imaging.

  8. A biological tissue adhesive and dissolvent system for intraocular tumor plaque radiotherapy: an in vivo animal model experiment.

    Science.gov (United States)

    Zloto, Ofira; Alezra, Dror; Sagiv, Oded; Belkin, Michael; Dai, Vicktoria Vishnevskia; Moroz, Iris; Greenberg, Gahl; Ben-Artsi, Elad; Fabian, Ido Didi

    2015-11-01

    To examine a novel biological adhesive and dissolvent system for plaque placement and removal using fibrin glue and urokinase, respectively, in an in vivo animal model. The study was performed on 23 rabbit eyes. Of these, eight underwent a technical feasibility study and ultrasonographic plaque displacement measurements, nine were examined clinically and by magnetic resonance imaging and histopathology for tissue reaction to the biological substances used, and in six the impact of fibrin glue as an orbital space occupier on intraocular pressure was assessed. In an additional ex vivo experiment, the glue's radiation attenuating properties were tested using an oncology EDR2 film. Plaque horizontal movement throughout follow-up (7-10 days) was negligible (0.5 ± 0.2 mm), and there was no tilting whatsoever. In the tissue response experiment, no adverse effects were recorded after application of fibrin or urokinase throughout the 21-day follow-up period. Interestingly, a circumscribed local inflammatory response was noted in tissue surrounding the fibrin glue, and persisted at 21 days. In the orbital space-occupying experiment, application of 1 cc fibrin glue did not cause a significant elevation in intraocular pressure (IOP) (P = 0.06), and in the ex vivo experiment, there was no significant difference between radiation readings with and without glue separation of the radioactive sources and film (P = 0.065). The adhesive and dissolvent system was feasible and safe for plaque placement and removal. It may be superior to conventional surgical plaque placement methods in eliminating the relatively common risk of plaque tilting and complications due to scleral suturing.

  9. In vivo antioxidant and hepatoprotective activity of methanolic extracts of Daucus carota seeds in experimental animals

    Science.gov (United States)

    Singh, Kamlesh; Singh, Nisha; Chandy, Anish; Manigauha, Ashish

    2012-01-01

    Objective To assess the In vivo antioxidFant and hepatoprotective activity of methanolic extract of Daucus carota (D. carota) seeds in experimental animals. Methods Methanolic extracts of D. carota seeds is used for hepatoprotection assessment. Oxidative stress were induced in rats by thioacetamide 100 mg/kg s.c, in four groups of rats (two test, standard and toxic control). Two test groups received D. carota seeds extract (DCSE) at doses of 200 mg/kg and 400 mg/kg. Standard group received silymarin (25 mg/kg) and toxic control received only thioacetamide. Control group received only vehicle. On the 8th day animals were sacrificed and liver enzyme like serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) were estimated in blood serum and antioxidant enzyme like superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GRD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and lipid peroxidation (LPO) were estimated in liver homogenate. Results A significant decrease in SGPT, SGOT and ALP levels was observed in all drug treated groups as compared to thioacetamide group (P < 0.001) and in case of antioxidant enzyme a significant (P < 0.001) increase in SOD, CAT, GRD, GPX and GST was observed in all drug treated groups as compared with thioacetamide group. But in case of LPO a significant (P < 0.001) reduction was observed as compared to toxic control group. Conclusions DCSE has contributed to the reduction of oxidative stress and the protection of liver in experimental rats. PMID:23569935

  10. Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

    Science.gov (United States)

    Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

  11. MEMS-based side-view endomicroscope for in vivo small animal imaging(Conference Presentation)

    Science.gov (United States)

    Duan, Xiyu; Li, Haijun; Li, Gaoming; Li, Xue; Oldham, Kenn R.; Wang, Thomas D.

    2017-02-01

    Tremendous advances have been made in technological development of whole body molecular imaging, including PET, SPECT, MRI, bioluminescence, and ultrasound. However, a great unmet need still exists for high resolution imaging of biological processes that occur in the epithelium, the thin layer of tissue where many important cancers originate. Confocal endomicroscopes designed with a fiber bundle are used in the clinic, but they can only create images in the horizontal plane. Imaging in the plane perpendicular to the tissue surface is also important because epithelial cells differentiate in the vertical direction. Subtle changes in normal tissue differentiation patterns can reveal the early expression of cancer biomarkers. In this work, we present a side-viewing confocal endomicroscope that can collect images in either horizontal or oblique plane using an integrated monolithic electrostatic 3D MEMS scanner. The endomicroscope can perform sub-cellular resolution imaging in both the horizontal plane and the oblique plane with FOVs of 500 x 700 µm2 and 500 x 200 µm2. A side-viewing probe will allow optimal contact between the imaging window and the luminal wall, which makes it easy to navigate in the hollow organ. The endomicroscope is packaged into a stainless steel tube with outer diameter of 4.2 mm, which can be used for both small animal and human GI tract imaging. We demonstrate in vivo imaging of colonic dysplasia in mice, showing the endomicroscope can potentially be used for early detection and staging of colon cancer.

  12. The Development of Animal Welfare in Finland and How People Perceive Animal Welfare : Case Study: Animals in Tourism: Zoos

    OpenAIRE

    Laatu, Suvi

    2013-01-01

    The aim of the thesis was to study how Finnish people perceive animal welfare in general and how they feel about animals in tourism purposes, more specifically in zoos. The thesis also contains information about Finnish animal legislation and how animal welfare has developed over time. The target group for the research was people who have visited zoos recently. The interviewed people were from different age groups. The theoretical framework consists of the following topics: people’s relations...

  13. Why do we study animal toxins?

    Science.gov (United States)

    ZHANG, Yun

    2015-01-01

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  14. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.M.; Gao, S.J.; Guo, X.F.; Sun, W.J. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Yan, Z.Q. [Department of Breast Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Wang, W.X.; Xu, Y.Q.; Lu, D. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China)

    2014-03-21

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

  15. In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study.

    Science.gov (United States)

    Krishna, Somashekar G; Modi, Rohan M; Kamboj, Amrit K; Swanson, Benjamin J; Hart, Phil A; Dillhoff, Mary E; Manilchuk, Andrei; Schmidt, Carl R; Conwell, Darwin L

    2017-05-14

    To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs). In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively. A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a "fern pattern" of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology. In vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.

  16. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Science.gov (United States)

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  17. An in vivo model of in situ implantation using pulmonary valved conduit in large animals under off-pump condition.

    Science.gov (United States)

    Wu, Hao; Xu, Zhi-wei; Liu, Xian-min; Gong, Da; Wan, Ju-yi; Xu, Xiu-fang; Zhou, Zi-fan; Li, Wen-bin

    2013-12-01

    The application of pulmonary valved conduit to reconstruct the continuity between right ventricles and pulmonary artery is one of the major surgeries. This study aimed to establish an in vivo model of in situ implantation using pulmonary valved conduit in large animals under off-pump condition to validate the long-term effects of artificial pulmonary valved conduit. Domesticate juvenile male sheep and tissue-engineered porcine pulmonary valved conduit were used for the experiment: 30 sheep, weighing (15 ± 3) kg (range 13 to 17 kg) were randomly divided into two groups which were all operated under general anesthesia by off-pump surgery (group 1) and left thoracotomy (group 2). Two different off-pump surgical methods were used to perform cannulation in sheep pulmonary artery to replace part of sheep pulmonary artery with pulmonary valved conduit which will work together with sheep pulmonary artery and valves. During the experiments, animal survival, complication rates, operating time and blood loss were recorded to compare the results between groups and to establish a surgical method with minimal invasion, simplicity, safety, and high success rates. In group 1, a total of 15 cases of surgeries were performed, in which two sheep died; the operative mortality was 13.3% (2/15). In group 2, a total of 15 cases of surgeries were performed, and the surgical mortality rate was 0 (0/15). The operation time and blood loss in group 2 was significantly better than that in group 1. The postoperative echocardiograms showed that, after the surgeries by these two methods, the blood flows were normal, and the valves can open and close freely. Autopsy after 6 months showed that the inner wall and the valves of pulmonary valved conduit were smooth with no thrombus formation. These two off-pump methods are feasible and safe with fewer traumas; but the second method is better and particularly suitable for the establishment of a juvenile animal model.

  18. An animal model to study regenerative endodontics.

    Science.gov (United States)

    Torabinejad, Mahmoud; Corr, Robert; Buhrley, Matthew; Wright, Kenneth; Shabahang, Shahrokh

    2011-02-01

    A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days. Copyright © 2011. Published by Elsevier Inc.

  19. Study Circles and Socio-cultural Animation

    Directory of Open Access Journals (Sweden)

    Vilma Malečkar

    2001-12-01

    Full Text Available Informal learning and participating in study circles is a way of applying the ideas of socio-cultural animation. It is based on the assumption that within a society there are mechanisms that institutions don't comprise and therefore don't fulfil various, often urgent needs deriving from everyday life and the community. What is going on here is identifying and solving burning problems; some of them have already become an integral part of the way of living in a community. Study circles as an informal phenomenon in Slovenia create new possibilities of social activities based on common learning and participating in a community.

  20. Study Circles and Socio-cultural Animation

    OpenAIRE

    Vilma Malečkar

    2001-01-01

    Informal learning and participating in study circles is a way of applying the ideas of socio-cultural animation. It is based on the assumption that within a society there are mechanisms that institutions don't comprise and therefore don't fulfil various, often urgent needs deriving from everyday life and the community. What is going on here is identifying and solving burning problems; some of them have already become an integral part of the way of living in a community. Study circles as an in...

  1. An instrumented pendulum system for measuring energy absorption during fracture insult to large animal joints in vivo.

    Science.gov (United States)

    Diestelmeier, B W; Rudert, M J; Tochigi, Y; Baer, T E; Fredericks, D C; Brown, T D

    2014-06-01

    For systematic laboratory studies of bone fractures in general and intra-articular fractures in particular, it is often necessary to control for injury severity. Quantitatively, a parameter of primary interest in that regard is the energy absorbed during the injury event. For this purpose, a novel technique has been developed to measure energy absorption in experimental impaction. The specific application is for fracture insult to porcine hock (tibiotalar) joints in vivo, for which illustrative intra-operative data are reported. The instrumentation allowed for the measurement of the delivered kinetic energy and of the energy passed through the specimen during impaction. The energy absorbed by the specimen was calculated as the difference between those two values. A foam specimen validation study was first performed to compare the energy absorption measurements from the pendulum instrumentation versus the work of indentation performed by an MTS machine. Following validation, the pendulum apparatus was used to measure the energy absorbed during intra-articular fractures created in 14 minipig hock joints in vivo. The foam validation study showed close correspondence between the pendulum-measured energy absorption and MTS-performed work of indentation. In the survival animal series, the energy delivered ranged from 31.5 to 48.3 Js (41.3±4.0, mean±s.d.) and the proportion of energy absorbed to energy delivered ranged from 44.2% to 64.7% (53.6%±4.5%). The foam validation results support the reliability of the energy absorption measure provided by the instrumented pendulum system. Given that a very substantial proportion of delivered energy passed--unabsorbed--through the specimens, the energy absorption measure provided by this novel technique arguably provides better characterization of injury severity than is provided simply by energy delivery.

  2. Krill products: an overview of animal studies.

    Science.gov (United States)

    Burri, Lena; Johnsen, Line

    2015-05-07

    Many animal studies have been performed with krill oil (KO) and this review aims to summarize their findings and give insight into the mechanism of action of KO. Animal models that have been used in studies with KO include obesity, depression, myocardial infarction, chronic low-grade and ulcerative inflammation and are described in detail. Moreover, studies with KO in the form of krill powder (KP) and krill protein concentrate (KPC) as a mix of lipids and proteins are mentioned and compared to the effects of KO. In addition, differences in tissue uptake of the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), when delivered in either phospholipid or triglyceride form, are addressed and the differential impact the delivery form has on gene expression profiles is explained. In our outlook, we try to highlight the potential of KO and KP supplementation in clinical settings and discuss health segments that have a high potential of showing krill product specific health benefits and warrant further clinical investigations.

  3. Krill Products: An Overview of Animal Studies

    Directory of Open Access Journals (Sweden)

    Lena Burri

    2015-05-01

    Full Text Available Many animal studies have been performed with krill oil (KO and this review aims to summarize their findings and give insight into the mechanism of action of KO. Animal models that have been used in studies with KO include obesity, depression, myocardial infarction, chronic low-grade and ulcerative inflammation and are described in detail. Moreover, studies with KO in the form of krill powder (KP and krill protein concentrate (KPC as a mix of lipids and proteins are mentioned and compared to the effects of KO. In addition, differences in tissue uptake of the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, when delivered in either phospholipid or triglyceride form, are addressed and the differential impact the delivery form has on gene expression profiles is explained. In our outlook, we try to highlight the potential of KO and KP supplementation in clinical settings and discuss health segments that have a high potential of showing krill product specific health benefits and warrant further clinical investigations.

  4. In vivo small animal imaging for early assessment of therapeutic efficacy of photodynamic therapy for prostate cancer

    Science.gov (United States)

    Fei, Baowei; Wang, Hesheng; Chen, Xiang; Meyers, Joseph; Mulvilhill, John; Feyes, Denise; Edgehouse, Nancy; Duerk, Jeffrey L.; Pretlow, Thomas G.; Oleinick, Nancy L.

    2007-03-01

    We are developing in vivo small animal imaging techniques that can measure early effects of photodynamic therapy (PDT) for prostate cancer. PDT is an emerging therapeutic modality that continues to show promise in the treatment of cancer. At our institution, a new second-generation photosensitizing drug, the silicon phthalocyanine Pc 4, has been developed and evaluated at the Case Comprehensive Cancer Center. In this study, we are developing magnetic resonance imaging (MRI) techniques that provide therapy monitoring and early assessment of tumor response to PDT. We generated human prostate cancer xenografts in athymic nude mice. For the imaging experiments, we used a highfield 9.4-T small animal MR scanner (Bruker Biospec). High-resolution MR images were acquired from the treated and control tumors pre- and post-PDT and 24 hr after PDT. We utilized multi-slice multi-echo (MSME) MR sequences. During imaging acquisitions, the animals were anesthetized with a continuous supply of 2% isoflurane in oxygen and were continuously monitored for respiration and temperature. After imaging experiments, we manually segmented the tumors on each image slice for quantitative image analyses. We computed three-dimensional T2 maps for the tumor regions from the MSME images. We plotted the histograms of the T2 maps for each tumor pre- and post-PDT and 24 hr after PDT. After the imaging and PDT experiments, we dissected the tumor tissues and used the histologic slides to validate the MR images. In this study, six mice with human prostate cancer tumors were imaged and treated at the Case Center for Imaging Research. The T2 values of treated tumors increased by 24 +/- 14% 24 hr after the therapy. The control tumors did not demonstrate significant changes of the T2 values. Inflammation and necrosis were observed within the treated tumors 24 hour after the treatment. Preliminary results show that Pc 4-PDT is effective for the treatment of human prostate cancer in mice. The small animal MR

  5. MRT letter: application of novel "in vivo cryotechnique" in living animal kidneys.

    Science.gov (United States)

    Li, Zilong; Li, Kai; Wang, Juan; Zhai, Xiaoyue; Wang, Lining; Ohno, Nobuhiko; Ohno, Shinichi

    2013-02-01

    To compare the influence of different fixation procedures on morphologic studies in living mice, and to identify the advantages of the "in vivo cryotechnique" (IVCT). We prepared mouse kidneys using four different fixation methods: conventional immersion-fixation, quick-freezing following resection of the kidney, quick-freezing following perfusion-fixation, and IVCT. Kidney glomeruli were noticeably contracted after conventional immersion-fixation or quick-freezing following resection compared to glomeruli from tissues preserved by the IVCT. With the IVCT, both albumin and IgG were colocalized exclusively along or within the glomerular capillary loops; however, immunoreactivity of these proteins in the other three methods was clearly detected in the Bowman's space and apical cytoplasm of the proximal tubules. With the IVCT, immunoreactivity of collagen type IV was very weak at the glomerular basement membrane (GBM) until microwave treatment, which increased its immunoreactivity. In contrast, the immunoreactivity was clearly detected at the GBM with or without microwave treatment with quick-freezing following perfusion-fixation. With quick-freezing following perfusion-fixation, aquaporin-1 (AQP-1) was irregularly distributed in a disorganized manner on the brush border and apical cell membrane along the proximal tubules. But AQP-1 was labeled intensely and regularly along the brush border and apical cell membrane andonly weakly along the basolateral membrane of the proximal tubules with the IVCT. The IVCT may reliably maintain soluble serum proteins and renal intrinsic proteins such as AQP-1 in situ and capture transient structures and functional changes in vivo. Copyright © 2012 Wiley Periodicals, Inc.

  6. Inaugurating the Study of Animal Metacognition.

    Science.gov (United States)

    Smith, J David

    2010-01-01

    Metacognition-the ability to monitor and control one's own cognition-is a sophisticated ability that reveals humans' reflective mind and consciousness. Researchers have begun to explore whether animals share humans' metacognitive capacity. This article reprises the original study that explored metacognition across species. A captive dolphin performed an auditory pitch-discrimination task using High/Low discrimination responses and an Uncertainty response with which he could decline to complete any trials he chose. He selectively declined the difficult trials near his discriminative threshold-just as humans do. This comparative exploration of metacognition required a trial-intensive titration of perceptual threshold and the training of a distinctive behavioral response. It could not have been conducted in the wild, though the naturalistic observation of dolphin uncertainty behaviors and risk-management strategies would no doubt yield complementary insights. The dolphin study inaugurated a new area of cross-species research. This research area opens a new window on reflective mind in animals, illuminates the phylogenetic emergence of metacognition, and may reveal the antecedents of human consciousness.

  7. The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

    Science.gov (United States)

    Holme, Ane M; Holm, Maia B; Roland, Marie C P; Horne, Hildegunn; Michelsen, Trond M; Haugen, Guttorm; Henriksen, Tore

    2017-08-02

    The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

  8. Cultural Consumer and Copyright: A Case Study of Anime Fansubbing

    OpenAIRE

    Lee, H. K.

    2011-01-01

    This article aims at discussing copyright and its infringement from the consumers’ perspective by examining ‘anime fansubbing’. Anime fansubbing refers to the practice in which avid anime (Japanese animation) fans copy anime, translate Japanese to another language, and subtitle and release a subtitled version on the Internet to share it with other fans, without permission from the copyright holder. The case study of English fansubbing of anime shows that this activity has been guided by fansu...

  9. In vitro and in vivo evaluation of a new large animal spirometry device using mainstream CO2 flow sensors.

    Science.gov (United States)

    Ambrisko, T D; Lammer, V; Schramel, J P; Moens, Y P S

    2014-07-01

    A spirometry device equipped with mainstream CO2 flow sensor is not available for large animal anaesthesia. To measure the resistance of a new large animal spirometry device and assess its agreement with reference methods for volume measurements. In vitro experiment and crossover study using anaesthetised horses. A flow partitioning device (FPD) equipped with 4 human CO2 flow sensors was tested. Pressure differences were measured across the whole FPD and across each sensor separately using air flows (range: 90-720 l/min). One sensor was connected to a spirometry monitor for in vitro volume (3, 5 and 7 l) measurements. These measurements were compared with a reference method. Five anaesthetised horses were used for tidal volume (VT) measurements using the FPD and a horse-lite sensor (reference method). Bland-Altman analysis, ANOVA and linear regression analysis were used for data analysis. Pressure differences across each sensor were similar suggesting equal flow partitioning. The resistance of the device increased with flow (range: 0.3-1.5 cmH2 O s/l) and was higher than that of the horse-lite. The limits of agreement for volume measurements were within -1 and 2% in vitro and -12 and 0% in vivo. Nine of 147 VT measurements in horses were outside of the ± 10% limits of acceptance but most of these erroneous measurements occurred with VTs lower than 4 l. The determined correction factor for volume measurements was 3.97 ± 0.03. The limits of agreement for volume measurements by the new device were within ± 10% using clinically relevant range of volumes. The new spirometry device can be recommended for measurement of VT in adult Warmblood horses. © 2013 EVJ Ltd.

  10. Enzyme-Directed Assembly of Nanoparticles in Tumors Monitored by In Vivo Whole Animal and Ex Vivo Super-Resolution Fluorescence Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Miao-Ping; Carlini, Andrea S.; Hu, Dehong; Barback, Christopher V.; Rush, Anthony M.; Hall, David J.; Orr, Galya; Gianneschi, Nathan C.

    2013-12-18

    Matrix metalloproteinase enzymes, overexpressed in HT-1080 human fibrocarcinoma tumors, were used to guide the accumulation and retention of an enzyme-responsive nanoparticle in a xenograft mouse model. The nanoparticles were prepared as micelles from amphiphilic block copolymers bearing a simple hydrophobic block, and a hydrophilic peptide brush. The polymers were end-labeled with Alexa Fluor 647 dyes leading to the formation of labeled micelles upon dialysis of the polymers from DMSO to aqueous buffer. This dye-labeling strategy allowed the presence of the retained material to be visualized via whole animal imaging in vivo, and in ex vivo organ analysis following intratumoral injection into HT-1080 xenograft tumors. We propose that the material is retained by virtue of an enzyme-induced accumulation process whereby particles change morphology from 20 nm spherical micelles to micron-scale aggregates, kinetically trapping them within the tumor. This hypothesis is tested here via an unprecedented super resolution fluorescence analysis of ex vivo tissue slices confirming a particle size increase occurs concomitantly with extended retention of responsive particles compared to unresponsive controls.

  11. Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results.

    Science.gov (United States)

    Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger

    2010-08-01

    implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months.  This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d-f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants.

  12. NIR-laser tissue welding in an in vivo guinea pig animal model

    Science.gov (United States)

    Sriramoju, Vidyasagar; Savage, Howard E.; Katz, A.; Chakraverty, Rahul; Budansky, Yuri; Podder, Rakhi; Davatgarzadeh, Naghmeh; Kartazayev, Uladzimir; Rosen, Richard B.; Alfano, R. R.

    2008-02-01

    Near infrared laser tissue welding (LTW) is achieved by subjecting the closely approximated surgically incised tissues to a laser beam at a wavelength that is absorbed by water in the tissue. Full thickness welds are accomplished with optimum laser power and penetration depths appropriate for the thickness of welded tissues. No extrinsic cross-linking or bonding materials are used. The absorbed laser energy increases the entropy of collagen in the tissue. In LTW, tissue water temperatures transiently rises to approximately 60° C, causing partial denaturing of collagen and other structural proteins due to breaking of hydrogen bonds, electrostatic interactions and some interchain covalent bonds for a short duration of time. This is followed by cross linking of proteins on either side of weld line, with reformation of the above mentioned bonds as the tissue cools, resulting in the formation of water tight full thickness welds. In this study, a cw fiber laser emitting at 1455 nm, corresponding to absorption by a water vibrational overtone, is used for in vivo LTW of surgical incisions made in the skin of guinea pigs under general anesthesia. The tensile strength and healing rates of the welded incisions are compared to suturing of similar incisions. Laser parameters, including power, scanning rates, exposure area, and exposure duration, are optimized to reduce thermal damage while maintaining tensile strength.

  13. A study in animal ethics in New Brunswick.

    OpenAIRE

    Schneider, B J

    2001-01-01

    Society uses animals in ever-increasing numbers and ways, providing ethical challenges. Decisions about animal use are guided by the social consensus ethic towards animals. Because there is no clear social consensus ethic, these decisions are difficult. Society's ethic is changing and a "new ethic" towards animals is emerging. This study addressed the need to better understand society's ethics towards animals. Qualitative research methodology (focus groups) was used to study 7 different anima...

  14. A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies.

    Science.gov (United States)

    Huber, K; Aichler, M; Sun, N; Buck, A; Li, Z; Fernandez, I E; Hauck, S M; Zitzelsberger, H; Eickelberg, O; Janssen, K P; Keller, U; Walch, A

    2014-10-01

    The aim of this study was to establish an ex vivo model for a faster optimisation of sample preparation procedures, for example matrix choice, in matrix-assisted laser desorption/ionisation (MALDI) drug imaging studies. The ionisation properties of four drugs, afatinib, erlotinib, irinotecan and pirfenidone, were determined in an ex vivo tissue experiment by spotting decreasing dilution series onto liver sections. Hereby, the drug signals were distinctly detectable using different matrix compounds, which allowed the selection of the optimal matrix for each drug. The analysis of afatinib and erlotinib yielded high drug signals with α-cyano-4-hydroxycinnamic acid matrix, whereas 2,3-dihydroxybenzoic acid was identified as optimal matrix for irinotecan and pirfenidone detection. Our method was validated by a MALDI drug imaging approach of in vivo treated mouse tissue resulting in corresponding findings, indicating the spotting method as an appropriate approach to determine the matrix of choice. The present study shows the accordance between the detection of ex vivo spotted drugs and in vivo administered drugs by MALDI-TOF and MALDI-FT-ICR imaging, which has not been demonstrated so far. Our data suggest the ex vivo tissue spotting method as an easy and reliable model to optimise MALDI imaging measurements and to predict drug detection in tissue sections derived from treated mice prior to the recruitment of laboratory animals, which helps to save animals, time and costs.

  15. Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals

    NARCIS (Netherlands)

    Klerk, Clara P. W.; Overmeer, Renée M.; Niers, Tatjana M. H.; Versteeg, Henri H.; Richel, Dick J.; Buckle, Tessa; van Noorden, Cornelis J. F.; van Tellingen, Olaf

    2007-01-01

    A relatively new strategy to longitudinally monitor tumor load in intact animals and the effects of therapy is noninvasive bioluminescence imaging (BLI). The validity of BLI for quantitative assessment of tumor load in small animals is critically evaluated in the present review. Cancer cells are

  16. Animals

    Energy Technology Data Exchange (ETDEWEB)

    Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)

    1997-10-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG). 68 refs.

  17. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

    This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

  18. Animal carcinogenicity studies: 1. Poor human predictivity.

    Science.gov (United States)

    Knight, Andrew; Bailey, Jarrod; Balcombe, Jonathan

    2006-02-01

    The regulation of human exposure to potentially carcinogenic chemicals constitutes society's most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or animal data also assessed by the World Health Organisation's International Agency for Research on Cancer (IARC), human carcinogenicity classifications were compatible with EPA classifications only for those 17 having at least limited human data (p = 0.5896). For those 111 primarily reliant on animal data, the EPA was much more likely than the IARC to assign carcinogenicity classifications indicative of greater human risk (p leading international authority on carcinogenicity assessments, and its significantly different human carcinogenicity classifications of identical chemicals indicate that: 1) in the absence of significant human data, the EPA is over-reliant on animal carcinogenicity data; 2) as a result, the EPA tends to over-predict carcinogenic risk; and 3) the true predictivity for human carcinogenicity of animal data is even poorer than is indicated by EPA figures alone. The EPA policy of erroneously assuming that tumours in animals are indicative of human carcinogenicity is implicated as a primary cause of these errors.

  19. Preliminary study for small animal preclinical hadrontherapy facility

    Energy Technology Data Exchange (ETDEWEB)

    Russo, G. [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); Pisciotta, P., E-mail: pietro.pisciotta@ibfm.cnr.it [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, Catania (Italy); Cirrone, G.A.P.; Romano, F. [National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, Catania (Italy); Cammarata, F.; Marchese, V.; Forte, G.I.; Lamia, D.; Minafra, L.; Bravatá, V. [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); Acquaviva, R. [University of Catania, Catania (Italy); Gilardi, M.C. [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); Cuttone, G. [National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, Catania (Italy)

    2017-02-21

    Aim of this work is the study of the preliminary steps to perform a particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. A well-defined dosimetric protocol was developed to explicate the steps needed in order to perform a precise proton irradiation in small animals and achieve a highly conformal dose into the target. A precise homemade positioning and holding system for small animals was designed and developed at INFN-LNS in Catania (Italy), where an accurate Monte Carlo simulation was developed, using Geant4 code to simulate the treatment in order to choose the best animal position and perform accurately all the necessary dosimetric evaluations. The Geant4 application can also be used to realize dosimetric studies and its peculiarity consists in the possibility to introduce the real target composition in the simulation using the DICOM micro-CT image. This application was fully validated comparing the results with the experimental measurements. The latter ones were performed at the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) facility at INFN-LNS by irradiating both PMMA and water solid phantom. Dosimetric measurements were performed using previously calibrated EBT3 Gafchromic films as a detector and the results were compared with the Geant4 simulation ones. In particular, two different types of dosimetric studies were performed: the first one involved irradiation of a phantom made up of water solid slabs where a layer of EBT3 was alternated with two different slabs in a sandwich configuration, in order to validate the dosimetric distribution. The second one involved irradiation of a PMMA phantom made up of a half hemisphere and some PMMA slabs in order to simulate a subcutaneous tumour configuration, normally used in preclinical studies. In order to evaluate the accordance between experimental and simulation results, two different statistical tests were made: Kolmogorov test and

  20. Preliminary study for small animal preclinical hadrontherapy facility

    Science.gov (United States)

    Russo, G.; Pisciotta, P.; Cirrone, G. A. P.; Romano, F.; Cammarata, F.; Marchese, V.; Forte, G. I.; Lamia, D.; Minafra, L.; Bravatá, V.; Acquaviva, R.; Gilardi, M. C.; Cuttone, G.

    2017-02-01

    Aim of this work is the study of the preliminary steps to perform a particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. A well-defined dosimetric protocol was developed to explicate the steps needed in order to perform a precise proton irradiation in small animals and achieve a highly conformal dose into the target. A precise homemade positioning and holding system for small animals was designed and developed at INFN-LNS in Catania (Italy), where an accurate Monte Carlo simulation was developed, using Geant4 code to simulate the treatment in order to choose the best animal position and perform accurately all the necessary dosimetric evaluations. The Geant4 application can also be used to realize dosimetric studies and its peculiarity consists in the possibility to introduce the real target composition in the simulation using the DICOM micro-CT image. This application was fully validated comparing the results with the experimental measurements. The latter ones were performed at the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) facility at INFN-LNS by irradiating both PMMA and water solid phantom. Dosimetric measurements were performed using previously calibrated EBT3 Gafchromic films as a detector and the results were compared with the Geant4 simulation ones. In particular, two different types of dosimetric studies were performed: the first one involved irradiation of a phantom made up of water solid slabs where a layer of EBT3 was alternated with two different slabs in a sandwich configuration, in order to validate the dosimetric distribution. The second one involved irradiation of a PMMA phantom made up of a half hemisphere and some PMMA slabs in order to simulate a subcutaneous tumour configuration, normally used in preclinical studies. In order to evaluate the accordance between experimental and simulation results, two different statistical tests were made: Kolmogorov test and

  1. Pre-clinical in vivo models for the screening of bone biomaterials for oral/craniofacial indications: focus on small-animal models.

    Science.gov (United States)

    Stavropoulos, Andreas; Sculean, Anton; Bosshardt, Dieter D; Buser, Daniel; Klinge, Björn

    2015-06-01

    Preclinical in vivo experimental studies are performed for evaluating proof-of-principle concepts, safety and possible unwanted reactions of candidate bone biomaterials before proceeding to clinical testing. Specifically, models involving small animals have been developed for screening bone biomaterials for their potential to enhance bone formation. No single model can completely recreate the anatomic, physiologic, biomechanic and functional environment of the human mouth and jaws. Relevant aspects regarding physiology, anatomy, dimensions and handling are discussed in this paper to elucidate the advantages and disadvantages of small-animal models. Model selection should be based not on the 'expertise' or capacities of the team, but rather on a scientifically solid rationale, and the animal model selected should reflect the question for which an answer is sought. The rationale for using heterotopic or orthotopic testing sites, and intraosseous, periosseous or extraskeletal defect models, is discussed. The paper also discusses the relevance of critical size defect modeling, with focus on calvarial defects in rodents. In addition, the rabbit sinus model and the capsule model in the rat mandible are presented and discussed in detail. All animal experiments should be designed with care and include sample-size and study-power calculations, thus allowing generation of meaningful data. Moreover, animal experiments are subject to ethical approval by the relevant authority. All procedures and the postoperative handling and care, including postoperative analgesics, should follow best practice. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. In vivo toxicity study of Lantana camara

    OpenAIRE

    Badakhshan Mahdi Pour; Sreenivasan Sasidharan

    2011-01-01

    Objective: To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. Methods: The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results: All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions: Methanolic...

  3. Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies; translational issues.

    Science.gov (United States)

    Smith, James O; Tayton, Edward R; Khan, Ferdous; Aarvold, Alexander; Cook, Richard B; Goodship, Allen; Bradley, Mark; Oreffo, Richard O C

    2017-04-01

    Binary blend polymers offer the opportunity to combine different desirable properties into a single scaffold, to enhance function within the field of tissue engineering. Previous in vitro and murine in vivo analysis identified a polymer blend of poly(l-lactic acid)-poly(ε-caprolactone) (PLLA:PCL 20:80) to have characteristics desirable for bone regeneration. Polymer scaffolds in combination with marrow-derived skeletal stem cells (SSCs) were implanted into mid-shaft ovine 3.5 cm tibial defects, and indices of bone regeneration were compared to groups implanted with scaffolds alone and with empty defects after 12 weeks, including micro-CT, mechanical testing and histological analysis. The critical nature of the defect was confirmed via all modalities. Both the scaffold and scaffold/SSC groups showed enhanced quantitative bone regeneration; however, this was only found to be significant in the scaffold/SSCs group (p = 0.04) and complete defect bridging was not achieved in any group. The mechanical strength was significantly less than that of contralateral control tibiae (p < 0.01) and would not be appropriate for full functional loading in a clinical setting. This study explored the hypothesis that cell therapy would enhance bone formation in a critical-sized defect compared to scaffold alone, using an external fixation construct, to bridge the scale-up gap between small animal studies and potential clinical translation. The model has proved a successful critical defect and analytical techniques have been found to be both valid and reproducible. Further work is required with both scaffold production techniques and cellular protocols in order to successfully scale-up this stem cell/binary blend polymer scaffold. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

  4. In vivo toxicity studies of fusarium mycotoxins in the last decade: a review.

    Science.gov (United States)

    Escrivá, L; Font, G; Manyes, L

    2015-04-01

    This review summarizes the information regarding the in vivo studies of Fusarium mycotoxins in the last decade. The most common studies are classified as subacute toxicity, subchronic toxicity, acute toxicity, toxicokinetic studies and teratogenicity in order of importance. The most used animals in in vivo studies are pigs, rats, chickens and mice. Fumonisin B1, deoxynivalenol, zearalenone, nivalenol and T-2 toxin are the most studied fusarotoxins. Studies with combinations of mycotoxins are also frequent, deoxynivalenol generally being one of them. The predominant route of administration is oral, administered mostly in the form of naturally contaminated feed. Other administration routes also used are intraperitoneal, intravenous and subcutaneous. In vivo research on Fusarium mycotoxins has increased since 2010 highlighting the need for such studies in the field of food and feed safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Digital Radiography for Determination of Primary Tooth Length: In Vivo and Ex Vivo Studies

    Directory of Open Access Journals (Sweden)

    Maria D. Basso

    2015-01-01

    Full Text Available Background. Methods for determining the root canal length of the primary tooth should yield accurate and reproducible results. In vitro studies show some limitations, which do not allow their findings to be directly transferred to a clinical situation. Aim. To compare the accuracy of radiographic tooth length obtained from in vivo digital radiograph with that obtained from ex vivo digital radiograph. Method. Direct digital radiographs of 20 upper primary incisors were performed in teeth (2/3 radicular resorption that were radiographed by an intraoral sensor, according to the long-cone technique. Teeth were extracted, measured, and mounted in a resin block, and then radiographic template was used to standardise the sensor-target distance (30 cm. The apparent tooth length (APTL was obtained from the computer screen by means of an electronic ruler accompanying the digital radiography software (CDR 2.0, whereas the actual tooth length (ACTL was obtained by means of a digital calliper following extraction. Data were compared to the ACTL by variance analysis and Pearson’s correlation test. Results. The values for APTL obtained from in vivo radiography were slightly underestimated, whereas those values obtained from ex vivo were slightly overestimated. No significance was observed (P≤0.48 between APTL and ACTL. Conclusion. The length of primary teeth estimated by in vivo and ex vivo comparisons using digital radiography was found to be similar to the actual tooth length.

  6. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [{sup 123}I]FP-CIT and a dedicated small animal SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf [Heinrich-Heine University, Clinic of Nuclear Medicine, Duesseldorf (Germany); Schramm, Nils [Research Center Juelich, Central Laboratory for Electronics, Juelich (Germany)

    2005-03-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [{sup 123}I]FP-CIT. [{sup 123}I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [{sup 123}I]FP-CIT scans with bone metabolism and perfusion scans obtained with {sup 99m}Tc-DPD and {sup 99m}Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [{sup 123}I]FP-CIT scans with images of brain perfusion obtained with {sup 99m}Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''{sub 3}) of 0.24{+-}0.26 (mean {+-} SD) and 1.09{+-}0.42, respectively (ttest, two-tailed, p<0.0001). Cortical V''{sub 3} values amounted to 0.05{+-}0.28 (methylphenidate) and 0.3{+-}0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [{sup 123}I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [{sup 123}I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and

  7. Recent advances in in vivo genotoxicity testing: prediction of carcinogenic potential using comet and micronucleus assay in animal models.

    Science.gov (United States)

    Kang, Seung Hun; Kwon, Jee Young; Lee, Jong Kwon; Seo, Young Rok

    2013-12-01

    Genotoxic events have been known as crucial step in the initiation of cancer. To assess the risk of cancer, genotoxicity assays, including comet, micronucleus (MN), chromosomal aberration, bacterial reverse, and sister chromatid exchange assay, can be performed. Compared with in vitro genotoxicity assay, in vivo genotoxicity assay has been used to verify in vitro assay result and definitely provide biological significance for certain organs or cell types. The comet assay can detect DNA strand breaks as markers of genotoxicity. Methods of the in vivo comet assay have been established by Japanese Center for the Validation of Alternative Methods (JaCVAM) validation studies depending on tissue and sample types. The MN can be initiated by segregation error and lagging acentric chromosome fragment. Methods of the in vivo MN assay have been established by Organization for Economic Co-operation and Development (OECD) test guidelines and many studies. Combining the in vivo comet and MN assay has been regarded as useful methodology for evaluating genetic damage, and it has been used in the assessment of potential carcinogenicity by complementarily presenting two distinct endpoints of the in vivo genotoxicity individual test. Few studies have investigated the quantitative relation between in vivo genotoxicity results and carcinogenicity. Extensive studies emphasizes that positive correlation is detectable. This review summarizes the results of the in vivo comet and MN assays that have investigated the genotoxicity of carcinogens as classified by the International Agency for Research on Cancer (IARC) carcinogenicity database. As a result, these genotoxicity data may provide meaningful information for the assessment of potential carcinogenicity and for implementation in the prevention of cancer.

  8. An in vivo evaluation of Brilliant Blue G in animals and humans.

    Science.gov (United States)

    Remy, M; Thaler, S; Schumann, R G; May, C A; Fiedorowicz, M; Schuettauf, F; Grüterich, M; Priglinger, S G; Nentwich, M M; Kampik, A; Haritoglou, C

    2008-08-01

    To evaluate the retinal toxicity of Brilliant Blue G (BBG) following intravitreal injection in rat eyes and examine the biocompatibility and the staining properties in humans. BBG was injected into the 11 rat eyes to evaluate toxic effects with balanced salt solution (BSS) serving as control. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts and by light microscopy 7 days later. In addition, BBG was applied during vitrectomy for macular hole (MH) (n = 15) or epiretinal membranes (ERM) (n = 3) in a prospective, non-comparative consecutive series of patients. Before and after surgery, all patients underwent a complete clinical examination including measurement of best corrected visual acuity (VA) and intraocular pressure, perimetry, fundus photography and optical coherence tomography. Patients were seen 1 day before surgery and then in approximately four weeks intervals. No significant reduction in RGC numbers and no morphological alterations were noted. A sufficient staining of the internal limiting membrane (ILM) was seen in patients with MH, while the staining pattern in ERM cases was patchy, indicating that parts of the ILM were peeled off along with the ERM in a variable extent. All MHs could be closed successfully. VA improved in 10 eyes (56%; 8/15 MH patients, 2/3 ERM patients), was unchanged in four eyes (22%; all MH patients) and was reduced in four eyes (22%; 3/15 MH, 1/3 ERM). No toxic effects attributable to the dye were noted during patient follow-up. The ultrastructure of tissue harvested during surgery was unremarkable. Brilliant Blue provides a sufficient and selective staining of the ILM. No retinal toxicity or adverse effects related to the dye were observed in animal and human studies. The long-term safety of this novel dye will have to be evaluated in larger patient series and a longer follow-up.

  9. In vivo toxicity study of Lantana camara.

    Science.gov (United States)

    Pour, Badakhshan Mahdi; Sasidharan, Sreenivasan

    2011-06-01

    To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Methanolic extract of L. camara is relatively safe on short-term exposure.

  10. Pulsed laser diode photoacoustic tomography (PLD-PAT) system for fast in vivo imaging of small animal brain

    Science.gov (United States)

    Upputuri, Paul Kumar; Kalva, Sandeep Kumar; Moothanchery, Mohesh; Pramanik, Manojit

    2017-03-01

    In recent years, high-repetition rate pulsed laser diode (PLD) was used as an alternative to the Nd:YAG lasers for photoacoustic tomography (PAT). The use of PLD makes the overall PAT system, a low-cost, portable, and high frame rate imaging tool for preclinical applications. In this work, we will present a portable in vivo pulsed laser diode based photoacoustic tomography (PLD-PAT) system. The PLD is integrated inside a circular scanning geometry. The PLD can provide near-infrared ( 803 nm) pulses with pulse duration 136 ns, and pulse energy 1.4 mJ / pulse at 7 kHz repetition rate. The system will be demonstrated for in vivo fast imaging of small animal brain. To enhance the contrast of brain imaging, experiments will be carried out using contrast agents which have strong absorption around laser excitation wavelength. This low-cost, portable small animal brain imaging system could be very useful for brain tumor imaging and therapy.

  11. In vitro calibration of a system for measurement of in vivo convective heat transfer coefficient in animals

    Directory of Open Access Journals (Sweden)

    Webster John G

    2006-10-01

    Full Text Available Abstract Background We need a sensor to measure the convective heat transfer coefficient during ablation of the heart or liver. Methods We built a minimally invasive instrument to measure the in vivo convective heat transfer coefficient, h in animals, using a Wheatstone-bridge circuit, similar to a hot-wire anemometer circuit. One arm is connected to a steerable catheter sensor whose tip is a 1.9 mm × 3.2 mm thin film resistive temperature detector (RTD sensor. We used a circulation system to simulate different flow rates at 39°C for in vitro experiments using distilled water, tap water and saline. We heated the sensor approximately 5°C above the fluid temperature. We measured the power consumed by the sensor and the resistance of the sensor during the experiments and analyzed these data to determine the value of the convective heat transfer coefficient at various flow rates. Results From 0 to 5 L/min, experimental values of h in W/(m2·K were for distilled water 5100 to 13000, for tap water 5500 to 12300, and for saline 5400 to 13600. Theoretical values were 1900 to 10700. Conclusion We believe this system is the smallest, most accurate method of minimally invasive measurement of in vivo h in animals and provides the least disturbance of flow.

  12. Understanding in vivo modelling of depression in non-human animals: a systematic review protocol

    DEFF Research Database (Denmark)

    Bannach-Brown, Alexandra; Liao, Jing; Wegener, Gregers

    2016-01-01

    experimental model(s) to induce or mimic a depressive-like phenotype. Data that will be extracted include the model or method of induction; species and gender of the animals used; the behavioural, anatomical, electrophysiological, neurochemical or genetic outcome measure(s) used; risk of bias...

  13. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Science.gov (United States)

    Botella, Cristina; Pérez-Ara, M Ángeles; Bretón-López, Juana; Quero, Soledad; García-Palacios, Azucena; Baños, Rosa María

    2016-01-01

    Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  14. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Cristina Botella

    Full Text Available Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31 versus an Augmented Reality system (N = 32 in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  15. Models of GH deficiency in animal studies.

    Science.gov (United States)

    Gahete, Manuel D; Luque, Raul M; Castaño, Justo P

    2016-12-01

    Growth hormone (GH) is a peptide hormone released from pituitary somatotrope cells that promotes growth, cell division and regeneration by acting directly through the GH receptor (GHR), or indirectly via hepatic insulin-like growth factor 1 (IGF1) production. GH deficiency (GHD) can cause severe consequences, such as growth failure, changes in body composition and altered insulin sensitivity, depending of the origin, time of onset (childhood or adulthood) or duration of GHD. The highly variable clinical phenotypes of GHD can now be better understood through research on transgenic and naturally-occurring animal models, which are widely employed to investigate the origin, phenotype, and consequences of GHD, and particularly the underlying mechanisms of metabolic disorders associated to GHD. Here, we reviewed the most salient aspects of GH biology, from somatotrope development to GH actions, linked to certain GHD types, as well as the animal models employed to reproduce these GHD-associated alterations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. In vivo imaging of endothelial cell adhesion molecule expression after radiosurgery in an animal model of arteriovenous malformation.

    Directory of Open Access Journals (Sweden)

    Newsha Raoufi-Rad

    Full Text Available Focussed radiosurgery may provide a means of inducing molecular changes on the luminal surface of diseased endothelium to allow targeted delivery of novel therapeutic compounds. We investigated the potential of ionizing radiation to induce surface expression of intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule 1 (VCAM-1 on endothelial cells (EC in vitro and in vivo, to assess their suitability as vascular targets in irradiated arteriovenous malformations (AVMs. Cultured brain microvascular EC were irradiated by linear accelerator at single doses of 0, 5, 15 or 25 Gy and expression of ICAM-1 and VCAM-1 measured by qRT-PCR, Western, ELISA and immunocytochemistry. In vivo, near-infrared (NIR fluorescence optical imaging using Xenolight 750-conjugated ICAM-1 or VCAM-1 antibodies examined luminal biodistribution over 84 days in a rat AVM model after Gamma Knife surgery at a single 15 Gy dose. ICAM-1 and VCAM-1 were minimally expressed on untreated EC in vitro. Doses of 15 and 25 Gy stimulated expression equally; 5 Gy was not different from the unirradiated. In vivo, normal vessels did not bind or retain the fluorescent probes, however binding was significant in AVM vessels. No additive increases in probe binding were found in response to radiosurgery at a dose of 15 Gy. In summary, radiation induces adhesion molecule expression in vitro but elevated baseline levels in AVM vessels precludes further induction in vivo. These molecules may be suitable targets in irradiated vessels without hemodynamic derangement, but not AVMs. These findings demonstrate the importance of using flow-modulated, pre-clinical animal models for validating candidate proteins for vascular targeting in irradiated AVMs.

  17. In vivo imaging of endothelial cell adhesion molecule expression after radiosurgery in an animal model of arteriovenous malformation.

    Science.gov (United States)

    Raoufi-Rad, Newsha; McRobb, Lucinda S; Lee, Vivienne S; Bervini, David; Grace, Michael; Ukath, Jaysree; Mchattan, Joshua; Sreenivasan, Varun K A; Duong, T T Hong; Zhao, Zhenjun; Stoodley, Marcus A

    2017-01-01

    Focussed radiosurgery may provide a means of inducing molecular changes on the luminal surface of diseased endothelium to allow targeted delivery of novel therapeutic compounds. We investigated the potential of ionizing radiation to induce surface expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells (EC) in vitro and in vivo, to assess their suitability as vascular targets in irradiated arteriovenous malformations (AVMs). Cultured brain microvascular EC were irradiated by linear accelerator at single doses of 0, 5, 15 or 25 Gy and expression of ICAM-1 and VCAM-1 measured by qRT-PCR, Western, ELISA and immunocytochemistry. In vivo, near-infrared (NIR) fluorescence optical imaging using Xenolight 750-conjugated ICAM-1 or VCAM-1 antibodies examined luminal biodistribution over 84 days in a rat AVM model after Gamma Knife surgery at a single 15 Gy dose. ICAM-1 and VCAM-1 were minimally expressed on untreated EC in vitro. Doses of 15 and 25 Gy stimulated expression equally; 5 Gy was not different from the unirradiated. In vivo, normal vessels did not bind or retain the fluorescent probes, however binding was significant in AVM vessels. No additive increases in probe binding were found in response to radiosurgery at a dose of 15 Gy. In summary, radiation induces adhesion molecule expression in vitro but elevated baseline levels in AVM vessels precludes further induction in vivo. These molecules may be suitable targets in irradiated vessels without hemodynamic derangement, but not AVMs. These findings demonstrate the importance of using flow-modulated, pre-clinical animal models for validating candidate proteins for vascular targeting in irradiated AVMs.

  18. Whole body in vivo examination of small animals by simultaneous X-rays/optical tomography: comparison between the reconstructions obtained with different types of fluorescent labels

    Science.gov (United States)

    Da Silva, A.; Bordy, T.; Debourdeau, M.; Dinten, J.-M.; Peltié, P.; Rizo, P.

    2007-07-01

    Small animal diffuse optical tomography is an appealing tool for the investigation of molecular events in cancer research and drug developments. The combination of the functional information brought by an optical system and the anatomical information delivered by X-Rays enables i) a fast multimodality animal examination; ii) the correlation between the biodistribution of the molecular probes and the morphology of the animal; iii) a more accurate optical data reconstructions by using the anatomy of the animal as a constrain in the reconstructions. A small animal multimodality tomographer for the coregistration of fluorescence optical signals and X-rays measurements is used in the present study. The optical system is composed with a CW laser and a CCD camera coupled with an appropriate combination of filters for the fluorescence detection. The animal is placed inside a transparent tube filled with an index matching fluid. The X-ray generator and detector have been positioned perpendicularly to the optical chain. Original optical calibration techniques have been developed in order to control at any time the alignment between the incident beam, the axis of the cylinder and the focus plan of the CCD. Specific developments have also been handled for obtaining the geometry correlation between optical and X-rays data reconstructions. This experimental setup is used in the present work for a study conducted on different kinds of fluorochromes for the purpose of the development of new molecular probes. The instrument is also used for in vivo biological study conducted on mice bearing tumors in the lungs, and tagged with near infrared optical probes (targeting probes such as Transferin- AlexaFluor 750 or such as RAFT-(cRGD) 4-Alexa700/Alexa750).

  19. A study in animal ethics in New Brunswick.

    Science.gov (United States)

    Schneider, B J

    2001-07-01

    Society uses animals in ever-increasing numbers and ways, providing ethical challenges. Decisions about animal use are guided by the social consensus ethic towards animals. Because there is no clear social consensus ethic, these decisions are difficult. Society's ethic is changing and a "new ethic" towards animals is emerging. This study addressed the need to better understand society's ethics towards animals. Qualitative research methodology (focus groups) was used to study 7 different animal-interest groups. Qualitative data analysis was computer-aided. The group ethical position towards animals of its own group interest was determined for each group. The animal welfare, companion animal, and veterinary groups took Rollin's Position, a position based on both the Utilitarian and the Rights Principles; the farmer and trapper groups the Utilitarian/Land Ethic position, a dual position based on actions producing the greatest amount of pleasure and the least amount of pain for the greatest number, and preserving the integrity, stability, and beauty of the biotic community; the hunter group the Utilitarian/Judeo-Christian position, a dual position based on actions producing the greatest amount of pleasure and the least amount of pain for the greatest number, and having dominion over animals; and the naturalist group took Rollin's Position/Land Ethic. All these groups perceived medium to extreme ethical responsibility towards animals of their own group's interest that are used by others. The study showed that the predicted "new ethic" towards animals is in New Brunswick society and it is Rollin's Position.

  20. Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies.

    Science.gov (United States)

    Abdelbary, Ghada A; Amin, Maha M; Zakaria, Mohamed Y

    2017-11-01

    Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance. Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis. The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated. An ex vivo corneal permeation study to determine the level of KET in the external eye tissue of albino rabbits and an in vivo assessment of the level of KET in the aqueous humors were performed. In vivo evaluation showed an increase in bioavailability up to 20-folds from the optimum KET proniosomal gel formula in the aqueous humor compared to drug suspension (KET-SP). The selected formulae were composed of spans being hydrophobic suggesting the potential use of a more hydrophobic surfactant as Span during the formulation of formulae. Factors that stabilize the vesicle membrane and increase the entrapment efficiency of KET (namely low HLB, long alkyl chain, high phase transition temperature) slowed down the release profile. Proniosomal gels as drug delivery carriers were proven to be a promising approach to increase corneal contact and permeation as well as retention time in the eye resulting in a sustained action and enhanced bioavailability.

  1. In Vivo Cytogenetic Studies on Aspartame

    Directory of Open Access Journals (Sweden)

    Entissar S. AlSuhaibani

    2010-01-01

    Full Text Available Aspartame (a-Laspartyl-L-phenylalanine 1-methylester is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol was investigated in vivo using chromosomal aberration (CA test and sister chromatid exchange (SCE test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight. Bone marrow cells isolated from femora were analyzed for chromosome aberrations and sister chromatid exchanges. Treatment with aspartame induced dose dependently chromosome aberrations at all concentrations while it did not induce sister chromatid exchanges. On the other hand, aspartame did not decrease the mitotic index (MI. However, statistical analysis of the results show that aspartame is not significantly genotoxic at low concentration.

  2. Precision-cut hamster liver slices as an ex vivo model to study amoebic liver abscess.

    Science.gov (United States)

    Carranza-Rosales, Pilar; Santiago-Mauricio, María Guadalupe; Guzmán-Delgado, Nancy Elena; Vargas-Villarreal, Javier; Lozano-Garza, Gerardo; Ventura-Juárez, Javier; Balderas-Rentería, Isaías; Morán-Martínez, Javier; Gandolfi, A Jay

    2010-10-01

    Entamoeba histolytica is the etiological agent of amoebiasis, the second cause of global morbidity and mortality due to parasitic diseases in humans. In approximately 1% of the cases, amoebas penetrate the intestinal mucosa and spread to other organs, producing extra-intestinal lesions, among which amoebic liver abscess (ALA) is the most common. To study ALA, in vivo and in vitro models are used. However, animal models may pose ethical issues, and are time-consuming and costly; and cell cultures represent isolated cellular lineages. The present study reports the infection of precision-cut hamster liver slices with Entamoeba histolytica trophozoites. The infection time-course, including tissue damage, parallels findings previously reported in the animal model. At the same time amoebic virulence factors were detected in the infected slices. This new model to study ALA is simple and reproducible, and employs less than 1/3 of the hamsters required for in vivo analyses. Copyright 2010 Elsevier Inc. All rights reserved.

  3. On the use of fluorescence lifetime imaging and dihydroethidium to detect superoxide in intact animals and ex vivo tissues: a reassessment.

    Science.gov (United States)

    Michalski, Radoslaw; Michalowski, Bartosz; Sikora, Adam; Zielonka, Jacek; Kalyanaraman, Balaraman

    2014-02-01

    Recently, D.J. Hall et al. reported that ethidium (E(+)) is formed as a major product of hydroethidine (HE) or dihydroethidium reaction with superoxide (O2(-)) in intact animals with low tissue oxygen levels (J. Cereb. Blood Flow Metab. 32:23-32, 2012). The authors concluded that measurement of E(+) is an indicator of O2(-) formation in intact brains of animals. This finding is in stark contrast to previous reports using in vitro systems showing that 2-hydroxyethidium, not ethidium, is formed from the reaction between O2(-) and HE. Published in vivo results support the in vitro findings. In this study, we performed additional experiments in which HE oxidation products were monitored under different fluxes of O2(-). Results from these experiments further reaffirm our earlier findings (H. Zhao et al., Free Radic. Biol. Med. 34:1359, 2003). We conclude that whether in vitro or in vivo, E(+) measured by HPLC or by fluorescence lifetime imaging is not a diagnostic marker product for O2(-) reaction with HE. © 2013 Published by Elsevier Inc.

  4. SYRCLE’s risk of bias tool for animal studies

    Science.gov (United States)

    2014-01-01

    Background Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation. Methods We provide an RoB tool for animal intervention studies (SYRCLE’s RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment. Results The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role. Conclusions SYRCLE’s RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies. PMID:24667063

  5. Application of Model Animals in the Study of Drug Toxicology

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

    Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

  6. Improved in Vivo Whole-Animal Detection Limits of Green Fluorescent Protein–Expressing Tumor Lines by Spectral Fluorescence Imaging

    Directory of Open Access Journals (Sweden)

    Jenny M. Tam

    2007-07-01

    Full Text Available Green fluorescent protein (GFP has been used for cell tracking and imaging gene expression in superficial or surgically exposed structures. However, in vivo murine imaging is often limited by several factors, including scatter and attenuation with depth and overlapping autofluorescence. The autofluorescence signals have spectral profiles that are markedly different from the GFP emission spectral profile. The use of spectral imaging allows separation and quantitation of these contributions to the total fluorescence signal seen in vivo by weighting known pure component profiles. Separation of relative GFP and autofluorescence signals is not readily possible using epifluorescent continuous-wave single excitation and emission bandpass imaging (EFI. To evaluate detection thresholds using these two methods, nude mice were subcutaneously injected with a series of GFP-expressing cells. For EFI, optimized excitation and emission bandpass filters were used. Owing to the ability to separate autofluorescence contributions from the emission signal using spectral imaging compared with the mixed contributions of GFP and autofluorescence in the emission signal recorded by the EFI system, we achieved a 300-fold improvement in the cellular detection limit. The detection limit was 3 × 103 cells for spectral imaging versus 1 × 106 cells for EFI. Despite contributions to image stacks from autofluorescence, a 100-fold dynamic range of cell number in the same image was readily visualized. Finally, spectral imaging was able to separate signal interference of red fluorescent protein from GFP images and vice versa. These findings demonstrate the utility of the approach in detecting low levels of multiple fluorescent markers for whole-animal in vivo applications.

  7. A method to study in vivo stability of DNA nanostructures.

    Science.gov (United States)

    Surana, Sunaina; Bhatia, Dhiraj; Krishnan, Yamuna

    2013-11-01

    DNA nanostructures are rationally designed, synthetic, nanoscale assemblies obtained from one or more DNA sequences by their self-assembly. Due to the molecularly programmable as well as modular nature of DNA, such designer DNA architectures have great potential for in cellulo and in vivo applications. However, demonstrations of functionality in living systems necessitates a method to assess the in vivo stability of the relevant nanostructures. Here, we outline a method to quantitatively assay the stability and lifetime of various DNA nanostructures in vivo. This exploits the property of intact DNA nanostructures being uptaken by the coelomocytes of the multicellular model organism Caenorhabditis elegans. These studies reveal that the present fluorescence based assay in coelomocytes of C. elegans is an useful in vivo test bed for measuring DNA nanostructure stability. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Development of high-resolution 4D in vivo-CT for visualization of cardiac and respiratory deformations of small animals

    Science.gov (United States)

    Sera, Toshihiro; Yokota, Hideo; Fujisaki, Kazuhiro; Fukasaku, Kazuaki; Tachibana, Hiroyuki; Uesugi, Kentaro; Yagi, Naoto; Himeno, Ryutaro

    2008-08-01

    The interest in small animal models of human diseases has generated a need to design a computed tomography (CT) system that operates at a microscopic level. It is particularly important to be able to visualize the dramatic rhythmical motion of organs such as the heart and lungs. In order to evaluate the motion of the heart and lungs of small animals (rats and mice), we developed in the present study a high-resolution 4D in vivo-CT system for small animals that uses synchrotron radiation. To reduce motion artifacts and the radiation dose, the projections were synchronized with airway pressure, the ECG, the x-ray shutter and the CCD shutter. For cardiovascular imaging, a blood pool contrast agent was injected and the data sets were acquired at several ECG points during the end-expiratory phase. For imaging of the lungs, the data sets were acquired at several airway pressures during diastole. The dynamic motion of the cardiovascular system (the ventricles and coronary arteries) and small airways (diameter > 250 µm of rats and 125 µm of mice) was visualized. This high-resolution imaging tool may be very useful for the development of novel drugs in murine models, in addition to its use in the study of cardiovascular and respiratory physiology.

  9. Book Review: Natures of Africa. Ecocriticism and Animal Studies in ...

    African Journals Online (AJOL)

    Book Review: Natures of Africa. Ecocriticism and Animal Studies in Contemporary Cultural Forms. Julia Martin. Abstract. Book Title: Natures of Africa. Ecocriticism and Animal Studies in Contemporary Cultural Forms. Book Author: Fiona Moolla (Ed.) Johannesburg: Wits University Press, 2016. 288pp. ISBN 9781868149131 ...

  10. SYRCLE's risk of bias tool for animal studies

    NARCIS (Netherlands)

    Hooijmans, C.R.; Rovers, M.M.; Vries, R.B.M. de; Leenaars, M.; Ritskes-Hoitinga, M.; Langendam, M.W.

    2014-01-01

    BACKGROUND: Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical

  11. Establishing a laboratory animal model from a transgenic animal: RasH2 mice as a model for carcinogenicity studies in regulatory science.

    Science.gov (United States)

    Urano, K; Tamaoki, N; Nomura, T

    2012-01-01

    Transgenic animal models have been used in small numbers in gene function studies in vivo for a period of time, but more recently, the use of a single transgenic animal model has been approved as a second species, 6-month alternative (to the routine 2-year, 2-animal model) used in short-term carcinogenicity studies for generating regulatory application data of new drugs. This article addresses many of the issues associated with the creation and use of one of these transgenic models, the rasH2 mouse, for regulatory science. The discussion includes strategies for mass producing mice with the same stable phenotype, including constructing the transgene, choosing a founder mouse, and controlling both the transgene and background genes; strategies for developing the model for regulatory science, including measurements of carcinogen susceptibility, stability of a large-scale production system, and monitoring for uniform carcinogenicity responses; and finally, efficient use of the transgenic animal model on study. Approximately 20% of mouse carcinogenicity studies for new drug applications in the United States currently use transgenic models, typically the rasH2 mouse. The rasH2 mouse could contribute to animal welfare by reducing the numbers of animals used as well as reducing the cost of carcinogenicity studies. A better understanding of the advantages and disadvantages of the transgenic rasH2 mouse will result in greater and more efficient use of this animal model in the future.

  12. Progress of genome wide association study in domestic animals.

    Science.gov (United States)

    Zhang, Hui; Wang, Zhipeng; Wang, Shouzhi; Li, Hui

    2012-08-22

    Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described.

  13. Studies on Animal Health Delivery Systems in Pastoral Areas in ...

    African Journals Online (AJOL)

    A study to identify animal health delivery systems to show how marginalized pastoral communities are accessing animal health services was conducted in Babati, Hanang and Mbulu Districts of Manyara Region. It was shown that livestock was the principal economic activity for pastoralists in Mbulu, Babati and Hanang and ...

  14. Optimal laser fiber rotational movement during photoselective vaporization of the prostate in a bovine ex-vivo animal model.

    Science.gov (United States)

    Osterberg, E Charles; Kauffman, Eric C; Kang, Hyun Wook; Koullick, Ed; Choi, Benjamin B

    2011-07-01

    Photoselective vaporization of the prostate (PVP) has emerged as an effective debulking procedure for prostatic urinary obstruction. Surgical technique for the most efficient vaporization has, however, received little scientific investigation. We used an ex-vivo bovine prostate model to investigate how variation in the angle of laser fiber rotational movement ("sweeping") affects prostate tissue vaporization efficiency. Experiments were conducted using the GreenLight™ HPS 120W laser system. A single surgeon performed a clinical PVP video analysis, forming the basis of our study design. Sixty bovine prostate specimens were vaporized using an ex-vivo chamber equipped with computer-assisted axial movements. Specimens were vaporized at a fixed sweeping speed (0.5 sweeps/sec) and variable sweeping angles (0, 15, 30, 60, 90, and 120 degrees). The volume of tissue vaporized was calculated from cross sections and compared by a two-sample t test. Clinical PVP video analysis of a single experienced surgeon showed a mean angle of 47.7 degrees with 25% of vaporization between 0 and 30 degrees. Ex-vivo analysis showed larger sweeping angles generated wider but more superficial vaporization defects, leading to smaller vaporized volumes. Specifically, vaporization volumes with angles of 0, 15, or 30 degrees were significantly greater than those with rotational angles of 45, 60, and 90 degrees (1.5-3.0 X; Pvaporization efficiency.

  15. [Toxoplasmosis and contact with animals: study of 390 cases].

    Science.gov (United States)

    Delgado García, G; Sánchez Torres, M

    1977-01-01

    Three hundred and ninety patients with suspected toxoplasmosis due to their contact with animales--they owned them, or work with them--are studied. The great significance of this way of acquiring the disease is stated. Every patient had a complement fixation test and an intradermal reaction test with toxoplasmine. An 85.2% positiveness to complement fixation, and a 64.1% to intradermal test were found among those patients who informed animal contact; a 70,6% positiveness to complement fixation, and a 56,2% to intradermal reaction was found in the patients who denied having any contact with animals. This showed both the importance of animal contact as well as other forms of transmission. The contacts were also studied, and the animals were classified according to J. Jira, the researcher: maximal, high, minimal and unreceptiveness to toxoplasma. The possibility of acquiring toxoplasmosis from other sources besides the close contact with animals must be taken into consideration.

  16. Evaluation of nonbiomedical and biomedical grade alginates for the transplantation of genetically modified articular chondrocytes to cartilage defects in a large animal model in vivo.

    Science.gov (United States)

    Heiligenstein, Susanne; Cucchiarini, Magali; Laschke, Matthias W; Bohle, Rainer M; Kohn, Dieter; Menger, Michael D; Madry, Henning

    2011-04-01

    Genetically modified chondrocytes embedded in alginate improve cartilage repair in experimental models, and alginates are clinically used for articular chondrocyte transplantation. In the present study, we tested the hypothesis that the alginate system allows for sustained transgene expression in cartilage defects in a preclinical large animal model in vivo. Primary cultures of ovine articular chondrocytes were transfected with the Photinus pyralis luc or the Escherichia coli lacZ genes in monolayer culture in vitro using eight different nonviral compounds. Optimally transfected chondrocytes were encapsulated in spheres composed of nonbiomedical or biomedical grade alginates for evaluation of luciferase expression, cell numbers and viabilities in vitro. Transfected chondrocytes encapsulated in spheres comprised of the different alginates were then implanted into osteochondral defects in the knee joints of sheep to examine the profiles of transgene expression in vivo. Ovine articular chondrocytes were efficiently transfected with FuGENE 6. Transgene expression was detectable after encapsulation in the alginates over 21 days in vitro. Transplantation of genetically modified chondrocytes to cartilage defects in vivo resulted in maximal transgene expression on day 1 after transfection, with a decrease by day 21, the longest time point evaluated. Remarkably, the reduction in luciferase activity was less pronounced when biomedical grade alginates were employed, compared to nonbiomedical grade alginates, suggesting that such alginates might be better suited to support elevated transgene expression after transplantation of genetically modified chondrocytes. This approach may be of value to study the effects of potential therapeutic genes upon cartilage repair in a clinically relevant setting. Copyright © 2011 John Wiley & Sons, Ltd.

  17. Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests?

    Science.gov (United States)

    Mueller, Ralf S; Olivry, Thierry

    2017-08-30

    The gold standard to diagnose adverse food reactions (AFRs) in the dog and cat is currently an elimination diet with subsequent provocation trials. However, those trials are inconvenient and client compliance can be low. Our objective was to systematically review the literature to evaluate in vivo and in vitro tests used to diagnose AFR in small animals. We searched three databases (CAB Abstracts, MEDLINE and Web of Science) for pertinent references on September 16, 2016. Among 71, 544 and 41 articles found in the CAB Abstract, MEDLINE and Web of Science databases, respectively, we selected 22 articles and abstracts from conference proceedings that reported data usable for evaluation of tests for AFR. Serum tests for food-specific IgE and IgG, intradermal testing with food antigens, lymphocyte proliferation tests, fecal food-specific IgE, patch, gastroscopic, and colonoscopic testing were evaluated. Testing for serum food-specific IgE and IgG showed low repeatability and, in dogs, a highly variable accuracy. In cats, the accuracy of testing for food-specific IgE was low. Lymphocyte proliferation tests were more frequently positive and more accurate in animals with AFR, but, as they are more difficult to perform, they remain currently a research tool. All other reported tests were only evaluated by individual studies with small numbers of animals. Negative patch test reactions have a very high negative predictability in dogs and could enable a choice of ingredients for the elimination diet in selected patients. Gastroscopic and colonoscopic testing as well as food-specific fecal IgE or food-specific serum IgG measurements appear less useful. Currently, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.

  18. Epidural application of spinal instrumentation particulate wear debris: a comprehensive evaluation of neurotoxicity using an in vivo animal model.

    Science.gov (United States)

    Cunningham, Bryan W; Hallab, Nadim J; Hu, Nianbin; McAfee, Paul C

    2013-09-01

    The introduction and utilization of motion-preserving implant systems for spinal reconstruction served as the impetus for this basic scientific investigation. The effect of unintended wear particulate debris resulting from micromotion at spinal implant interconnections and bearing surfaces remains a clinical concern. Using an in vivo rabbit model, the current study quantified the neural and systemic histopathological responses following epidural application of 11 different types of medical-grade particulate wear debris produced from spinal instrumentation. A total of 120 New Zealand White rabbits were equally randomized into 12 groups based on implant treatment: 1) sham (control), 2) stainless steel, 3) titanium alloy, 4) cobalt chromium alloy, 5) ultra-high molecular weight polyethylene (UHMWPe), 6) ceramic, 7) polytetrafluoroethylene, 8) polycarbonate urethane, 9) silicone, 10) polyethylene terephthalate, 11) polyester, and 12) polyetheretherketone. The surgical procedure consisted of a midline posterior approach followed by resection of the L-6 spinous process and L5-6 ligamentum flavum, permitting interlaminar exposure of the dural sac. Four milligrams of the appropriate treatment material (Groups 2-12) was then implanted onto the dura in a dry, sterile format. All particles (average size range 0.1-50 μm in diameter) were verified to be endotoxin free prior to implantation. Five animals from each treatment group were sacrificed at 3 months and 5 were sacrificed at 6 months postoperatively. Postmortem analysis included epidural cultures and histopathological assessment of local and systemic tissue samples. Immunocytochemical analysis of the spinal cord and overlying epidural fibrosis quantified the extent of proinflammatory cytokines (tumor necrosis factor-α, tumor necrosis factor-β, interleukin [IL]-1α, IL-1β, and IL-6) and activated macrophages. Epidural cultures were negative for nearly all cases, and there was no evidence of particulate debris or

  19. Why study the use of animal products in traditional medicines?

    Directory of Open Access Journals (Sweden)

    Rosa Ierecê L

    2005-08-01

    Full Text Available Abstract The World Health Organization (WHO estimates that as many as 80% of the world's more than six billion people rely primarily on animal and plant-based medicines. The healing of human ailments by using therapeutics based on medicines obtained from animals or ultimately derived from them is known as zootherapy. The phenomenon of zootherapy is marked both by a broad geographical distribution and very deep historical origins. Despite their importance, studies on the therapeutic use of animals and animal parts have been neglected, when compared to plants. This paper discusses some related aspects of the use of animals or parts thereof as medicines, and their implications for ecology, culture (the traditional knowledge, economy, and public health.

  20. Why study the use of animal products in traditional medicines?

    Science.gov (United States)

    Alves, Rômulo R N; Rosa, Ierecê L

    2005-08-30

    The World Health Organization (WHO) estimates that as many as 80% of the world's more than six billion people rely primarily on animal and plant-based medicines. The healing of human ailments by using therapeutics based on medicines obtained from animals or ultimately derived from them is known as zootherapy. The phenomenon of zootherapy is marked both by a broad geographical distribution and very deep historical origins. Despite their importance, studies on the therapeutic use of animals and animal parts have been neglected, when compared to plants. This paper discusses some related aspects of the use of animals or parts thereof as medicines, and their implications for ecology, culture (the traditional knowledge), economy, and public health.

  1. A Study on Impact of Anime on Tourism in Japan : A Case of "Anime Pilgrimage"

    OpenAIRE

    Okamoto, Takeshi

    2009-01-01

    Recently, in Japan, some of anime fans make "Anime Pilgrimage" which is a kind of tourist behavior. People making an "Anime Pilgrimage" are called "Anime Pilgrims". Some cases of "Anime Pilgrimage" evolve into movement of regional development. In these cases "Anime Pilgrims" collaborate with local residents spontaneously, hold an event and make souvenir or goods. The objective of this paper is to clarify characteristics of "Anime Pilgrim" using questionnaire survey and face-to-face interviews.

  2. Farm workers’ perception of animal welfare – A Danish Study

    DEFF Research Database (Denmark)

    Anneberg, Inger

    2017-01-01

    The welfare of farm animals depends on development in production systems, economic drivers and regulation but also human factors – such as farmers’ perceptions of animal welfare, management strategies, communication, knowledge and training. In this study I have examined the perception of animal...... welfare among farm workers employed at five different Danish farms (pig, dairy cattle and mink). The methodology employed ethnographic field studies during daily work at the farms and qualitative interviews with 23 farm workers, of which some are of Danish nationality and others from other countries....

  3. Persistence of DNA studied in different ex vivo and in vivo rat models simulating the human gut situation

    NARCIS (Netherlands)

    Wilcks, A.; Hoek, van A.H.A.M.; Joosten, R.G.; Jacobsen, B.B.L.; Aarts, H.J.M.

    2004-01-01

    This study aimed to evaluate the possibility of DNA sequences from genetically modified plants to persist in the gastrointestinal (GI) tract. PCR analysis and transformation assays were used to study DNA persistence and integrity in various ex vivo and in vivo systems using gnotobiotic rats. DNA

  4. Applicability of handmade expanded polytetrafluoroethylene trileaflet-valved conduits for pulmonary valve reconstruction: An ex vivo and in vivo study.

    Science.gov (United States)

    Kan, Chung-Dann; Wang, Jieh-Neng; Chen, Wei-Ling; Lu, Pong-Jeu; Chan, Ming-Yao; Lin, Chia-Hung; Hsieh, Wan-Chin

    2017-09-20

    The handmade expanded polytetrafluoroethylene (ePTFE) trileaflet-valved conduit could potentially be used as a substitute pulmonary valve replacement material, especially in children. The current study investigated (1) the function of the ePTFE trileaflet-valved conduits in an ex vivo experimental system and (2) the short-term performance of the conduit in a porcine model to verify its clinical applicability. The competency of the ePTFE trileaflet-valved conduits was estimated through ex vivo (using a pulmonary mock circulation loop) and in vivo (in a porcine model with a damaged pulmonary valve) experiments. Explants were examined by gross morphology and histopathologic examination. In the ex vivo experiment, the ePTFE trileaflet-valved conduits were determined to effectively increase mean pulmonary pressure from 10.2 to 14.4 mm Hg compared with defective silicon-valved conduits. In addition, the regurgitation fraction value of ePTFE trileaflet-valved conduits was 15.9% to 18.1%, which was significantly better than the defective valve conduits (regurgitation fraction = 73.5%-85.7%). In the in vivo experiment, the valved conduits were confirmed to be with good valve position maintenance, and the valve and leaflets showed no signs of thickening or peeling after a short-term implantation period. There were also no significant signs of inflammation reaction on histopathologic examination. The ePTFE trileaflet-valved conduits for pulmonary valve reconstruction showed acceptable performance and outcomes in the ex vivo and in vivo experiments. The ePTFE trileaflet-valved conduit may be clinically useful, although additional studies in animals should be conducted to determine its long-term outcomes. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  5. A nanoparticle dispersion method for in vitro and in vivo nanotoxicity study.

    Science.gov (United States)

    Kim, Seong C; Chen, Da-Ren; Qi, Chaolong; Gelein, Robert M; Finkelstein, Jacob N; Elder, Alison; Bentley, Karen; Oberdörster, Günter; Pui, David Y H

    2010-03-01

    The dispersion in air of nanoparticles of different sizes, materials and morphologies with controlled agglomeration involving aerosol delivery for in vivo and in vitro studies is one of the most difficult challenges in the field of nanoparticle toxicology. We describe here a nanoparticle dispersion system using an electrospray method to deliver airborne nanoparticles (approximately 10-100 nm) with spatial uniformity and controllable particle concentration for in vitro and in vivo studies. With the dispersion method, single nanoparticles (polystyrene latex particles, TiO(2), Au, Mn, quantum dots, and carbon nanotubes) can be delivered to cells and animals via the air. The degree of agglomeration can be controlled by changing the suspension feeding rate to simulate realistic conditions for exposure studies.

  6. Animal subjectivity : a study into philosophy and theory of animal experience

    NARCIS (Netherlands)

    Lijmbach, S.

    1998-01-01

    For many people, laypeople as well as animal scientists and philosophers, animal welfare involves animal feelings. Scientifically, however, animal feelings are problematic. In the concluding remarks of a conference about the welfare of domestic animals in 1994, for example, two questions

  7. In vivo study of human skin using pulsed terahertz radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pickwell, E [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Cole, B E [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Fitzgerald, A J [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Pepper, M [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Wallace, V P [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom)

    2004-05-07

    Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

  8. The importance of animal studies in Exercise Science

    Directory of Open Access Journals (Sweden)

    Kátia De Angelis

    2017-05-01

    Full Text Available Abstract The validity and relevance of research with animals for the development of knowledge in Exercise Science have for long been discussed. Given the complexity of the biological systems, the use of animal models offers a significant contribution to uncover new findings about acute and chronic effects of exercise, particularly when these studies in humans have limitations and ethical implications. There have been notable findings using experimental animals either in basic sciences or in clinical studies involving physiology, pharmacology, genetic, biochemistry, urology, endocrinology and cancer. This article presents a brief review of scientific research using animal models with a focus on exercise training as an effective tool for the prophylaxis and treatment of different pathological processes, which are the basis of many concepts taught and used in undergraduate courses and graduate programs, as well as in new researches showed in scientific conference meetings in numerous areas of science.

  9. Design of a dual slot antenna for small animal microwave ablation studies.

    Science.gov (United States)

    Moon, Tyler J; Brace, Christopher L

    2016-08-01

    This study presents the development of a dual-slot antenna for small animal tumor ablation. By using a dual-slot design at 8 GHz, it was hypothesized that smaller and more spherical ablations can be produced. After computer-aided design optimization, antennas were fabricated and ablations performed at 5-20 W for 15-120 s with the objective of creating ablations with a diameter/length aspect ratio of at least 0.9. The new dual-slot design at 8 GHz created significantly more spherical ablations than a commercial antenna at 2.45 GHz in ex vivo liver tissue (Average Aspect Ratio 0.8081 vs. 0.4532, p studies confirmed the highly spherical results ex vivo. Initial testing shows that the dual-slot antenna and 8 GHz generator can be used to ablate tumors in mice.

  10. Compounds used to produce cloned animals are genotoxic and mutagenic in mammalian assays in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, R.J. [Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto de Biociências de Rio Claro, Universidade Estadual Paulista, Rio Claro, SP (Brazil); Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica, Núcleo de Hospital Universitário, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Programa de Pós-Graduação em Saúde em Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina “Dr. Hélio Mandetta”, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Mantovani, M.S.; Silva, A.F. da [Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR (Brazil); Pesarini, J.R. [Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica, Núcleo de Hospital Universitário, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Programa de Pós-Graduação em Saúde em Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina “Dr. Hélio Mandetta”, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Mauro, M.O. [Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica, Núcleo de Hospital Universitário, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Programa de Doutorado em Biotecnologia e Biodiversidade - Rede Pró Centro-Oeste, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Ribeiro, L.R. [Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto de Biociências de Rio Claro, Universidade Estadual Paulista, Rio Claro, SP (Brazil); Programa de Pós-Graduação em Patologia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP (Brazil)

    2014-03-28

    The compounds 6-dimethylaminopurine and cycloheximide promote the successful production of cloned mammals and have been used in the development of embryos produced by somatic cell nuclear transfer. This study investigated the effects of 6-dimethylaminopurine and cycloheximide in vitro, using the thiazolyl blue tetrazolium bromide colorimetric assay to assess cytotoxicity, the trypan blue exclusion assay to assess cell viability, the comet assay to assess genotoxicity, and the micronucleus test with cytokinesis block to test mutagenicity. In addition, the comet assay and the micronucleus test were also performed on peripheral blood cells of 54 male Swiss mice, 35 g each, to assess the effects of the compounds in vivo. The results indicated that both 6-dimethylaminopurine and cycloheximide, at the concentrations and doses tested, were cytotoxic in vitro and genotoxic and mutagenic in vitro and in vivo, altered the nuclear division index in vitro, but did not diminish cell viability in vitro. Considering that alterations in DNA play important roles in mutagenesis, carcinogenesis, and morphofunctional teratogenesis and reduce embryonic viability, this study indicated that 6-dimethylaminopurine and cycloheximide utilized in the process of mammalian cloning may be responsible for the low embryo viability commonly seen in nuclear transfer after implantation in utero.

  11. THE STUDY OF CHEMICAL COMPOSITION FOR ANIMAL FATS DURING STORAGE

    OpenAIRE

    Flavia Pop; Cornel Laslo

    2009-01-01

    In this article the chemical composition for 3 types of animal fats (pork fat, beef tallow and buffalo tallow), following the variation of saturated and unsaturated fatty acids proportion during freezing storage was studied. Determination of chemical composition of animal fats is important in establishing organoleptic and physico-chemical parameters, the variation of them in time, nature and proportion of fatty acids conferring specific characteristics to them. For pork fat was determined the...

  12. Nanomedicine for Inner Ear Diseases: A Review of Recent In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Dong-Kee Kim

    2017-01-01

    Full Text Available Nanoparticles are promising therapeutic options for inner ear disease. In this report, we review in vivo animal studies in the otologic field using nanoparticles over the past 5 years. Many studies have used nanoparticles to deliver drugs, genes, and growth factors, and functional and morphological changes have been observed. The constituents of nanoparticles are also diversifying into various biocompatible materials, including poly(lactic-co-glycolic acid (PLGA. The safe and effective delivery of drugs or genes in the inner ear will be a breakthrough for the treatment of inner ear diseases, including age-related hearing loss.

  13. Risk estimates for silicosis: comparison of animal and human studies

    Energy Technology Data Exchange (ETDEWEB)

    Tran, C.L.; Miller, B.G.; Soutar, C.A.

    2005-09-15

    A risk assessment has been conducted for lung fibrosis from inhaled crystalline silica that follows the traditional approach of extrapolation from animal studies, and the results compared with observed human risks based on epidemiological studies. Bio-mathematical modelling was applied to the available animal data to estimate the NOAEL for inflammation. The resulting estimate for the rat is 0.1 mg.m{sup -3}. Conventional scaling and extrapolation methods recommended by the US EPA have then been applied to estimate a human acceptable average exposure limit. This resulted in an estimate of about 0.001 mg.m{sup -3}. The risk estimates were compared with human risk estimates for fibrosis based on epidemiological data. These comprised ACGIH summary conclusions on the risk estimates provided by epidemiological studies, and the risks demonstrated by one epidemiological study, of Scottish coalworkers, with unusually detailed exposure information. The average exposure limits implied by the risk estimates from the epidemiological studies ranged from 0.01 mg.m{sup -3} to about 0.05 mg.m{sup -3}, some 9 to 45 times higher than the limits derived from the animal studies. The conventional uncertainty factors applied in the animal-based risk estimates may be over-precautionary. Extension of the biomathematical model to extrapolate from animals to humans would provide a sounder basis for extrapolation than the present uncertainty factors. 18 refs., 5 figs., 5 tabs., 2 apps.

  14. Real-time temperature monitoring during radiofrequency treatments on ex-vivo animal model by fiber Bragg grating sensors

    Science.gov (United States)

    Palumbo, Giovanna; Tosi, Daniele; Schena, Emiliano; Massaroni, Carlo; Ippolito, Juliet; Verze, Paolo; Carlomagno, Nicola; Tammaro, Vincenzo; Iadicicco, Agostino; Campopiano, Stefania

    2017-05-01

    Fiber Bragg Grating (FBG) sensors applied to bio-medical procedures such as surgery and rehabilitation are a valid alternative to traditional sensing techniques due to their unique characteristics. Herein we propose the use of FBG sensor arrays for accurate real-time temperature measurements during multi-step RadioFrequency Ablation (RFA) based thermal tumor treatment. Real-time temperature monitoring in the RF-applied region represents a valid feedback for the success of the thermo-ablation procedure. In order to create a thermal multi-point map around the tumor area to be treated, a proper sensing configuration was developed. In particular, the RF probe of a commercial medical instrumentation, has been equipped with properly packaged FBGs sensors. Moreover, in order to discriminate the treatment areas to be ablated as precisely as possible, a second array 3.5 cm long, made by several FBGs was used. The results of the temperature measurements during the RFA experiments conducted on ex-vivo animal liver and kidney tissues are presented herein. The proposed FBGs based solution has proven to be capable of distinguish different and consecutive discharges and for each of them, to measure the temperature profile with a resolution of 0.1 °C and a minimum spatial resolution of 5mm. Based upon our experiments, it is possible to confirm that the temperature decreases with distance from a RF peak ablation, in accordance with RF theory. The proposed solution promises to be very useful for the surgeon because a real-time temperature feedback allows for the adaptation of RFA parameters during surgery and better delineates the area under treatment.

  15. METHOD FOR SIMULTANEOUS 90SR AND 137CS IN-VIVO MEASUREMENTS OF SMALL ANIMALS AND OTHER ENVIRONMENTAL MEDIA DEVELOPED FOR THE CONDITIONS OF THE CHERNOBYL EXCLUSION ZONE

    Energy Technology Data Exchange (ETDEWEB)

    Farfan, E.; Jannik, T.

    2011-10-01

    To perform in vivo simultaneous measurements of the {sup 90}Sr and {sup 137}Cs content in the bodies of animals living in the Chernobyl Exclusion Zone (ChEZ), an appropriate method and equipment were developed and installed in a mobile gamma beta spectrometry laboratory. This technique was designed for animals of relatively small sizes (up to 50 g). The {sup 90}Sr content is measured by a beta spectrometer with a 0.1 mm thick scintillation plastic detector. The spectrum processing takes into account the fact that the measured object is 'thick-layered' and contains a comparable quantity of {sup 137}Cs, which is a characteristic condition of the ChEZ. The {sup 137}Cs content is measured by a NaI scintillation detector that is part of the combined gamma beta spectrometry system. For environmental research performed in the ChEZ, the advantages of this method and equipment (rapid measurements, capability to measure live animals directly in their habitat, and the capability of simultaneous {sup 90}Sr and {sup 137}Cs measurements) far outweigh the existing limitations (considerations must be made for background radiation and the animal size, skeletal shape and body mass). The accuracy of these in vivo measurements is shown to be consistent with standard spectrometric and radiochemical methods. Apart from the in vivo measurements, the proposed methodology, after a very simple upgrade that is also described in the article, works even more accurately with samples of other media, such as soil and plants.

  16. In-vivo laser induced urethral stricture animal model for investigating the potential of LDR-brachytherapy

    Science.gov (United States)

    Sroka, Ronald; Lellig, Katja; Bader, Markus; Stief, Christian; Weidlich, Patrick; Wechsel, G.; Assmann, Walter; Becker, R.; Fedorova, O.; Khoder, Wael

    2015-02-01

    documented for correlation. At further 28 days after catheter removal the animals were euthanasized and the urethra tissue was harvested. Histological examination of tissue with assessment of radiation damage, fibrotic and inflammatory changes were performed. After deblinding histological finding were correlated with the applied dose. Results: All animals developed a stricture, while 15/18 (83,3%) showed a significant, high grade stricture with more than 90% lumen narrowing. Histopathological examination including evaluation of urethral inflammation, fibrosis and collagen content were investigated in additional 6 rabbits confirming the former findings. No rabbits died prematurely during the study. The experiments showed that the procedure of the application of radioactive catheter was safe without any problems in contamination and protection handling. The combination of internal urethrotomy and LDR-brachytherapy results in a stricture free rate of 66.7% in the 15-Gy group, compared with only 33.3% among animals from the 0- and 30-Gy groups. Furthermore histological classification of inflammation and fibrosis of 0 Gy and 15 Gy showed similar extent. Conclusion: This new method of laser induced urethral stricture was very efficient and showed a high reproducibility, thus being useful for studying stenosis treatments. The experiments showed that application of local β-irradiation by means of radioactive catheters modulated the stenosis development. This kind of LDR-brachytherapy shows potential for prophylaxis of urethral stricture. As this was an animal pilot experiment a clinical dose response study is needed.

  17. The Potential of Adaptive Design in Animal Studies.

    Science.gov (United States)

    Majid, Arshad; Bae, Ok-Nam; Redgrave, Jessica; Teare, Dawn; Ali, Ali; Zemke, Daniel

    2015-10-12

    Clinical trials are the backbone of medical research, and are often the last step in the development of new therapies for use in patients. Prior to human testing, however, preclinical studies using animal subjects are usually performed in order to provide initial data on the safety and effectiveness of prospective treatments. These studies can be costly and time consuming, and may also raise concerns about the ethical treatment of animals when potentially harmful procedures are involved. Adaptive design is a process by which the methods used in a study may be altered while it is being conducted in response to preliminary data or other new information. Adaptive design has been shown to be useful in reducing the time and costs associated with clinical trials, and may provide similar benefits in preclinical animal studies. The purpose of this review is to summarize various aspects of adaptive design and evaluate its potential for use in preclinical research.

  18. The Potential of Adaptive Design in Animal Studies

    Directory of Open Access Journals (Sweden)

    Arshad Majid

    2015-10-01

    Full Text Available Clinical trials are the backbone of medical research, and are often the last step in the development of new therapies for use in patients. Prior to human testing, however, preclinical studies using animal subjects are usually performed in order to provide initial data on the safety and effectiveness of prospective treatments. These studies can be costly and time consuming, and may also raise concerns about the ethical treatment of animals when potentially harmful procedures are involved. Adaptive design is a process by which the methods used in a study may be altered while it is being conducted in response to preliminary data or other new information. Adaptive design has been shown to be useful in reducing the time and costs associated with clinical trials, and may provide similar benefits in preclinical animal studies. The purpose of this review is to summarize various aspects of adaptive design and evaluate its potential for use in preclinical research.

  19. Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.

    Directory of Open Access Journals (Sweden)

    Xinhua Chen

    Full Text Available BACKGROUND AND AIM: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. MATERIALS AND METHODS: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. RESULTS: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. CONCLUSION: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.

  20. Persistence of DNA studied in different ex vivo and in vivo rat models simulating the human gut situation

    DEFF Research Database (Denmark)

    Wilcks, Andrea; van Hoek, A.H.A.M.; Joosten, R.G.

    2004-01-01

    This study aimed to evaluate the possibility of DNA sequences from genetically modified plants to persist in the gastrointestinal (GI) tract. PCR analysis and transformation assays were used to study DNA persistence and integrity in various ex vivo and in vivo systems using gnotobiotic rats. DNA...... studied was either plasmid DNA, naked plant DNA or plant DNA embedded in maize flour. Ex vivo experiments performed by incubating plant DNA in intestinal samples, showed that DNA is rapidly degraded in the upper part of the GI tract whereas degradation is less severe in the lower part. In contrast...

  1. Animal models to study the pathogenesis of human and animal Clostridium perfringens infections.

    Science.gov (United States)

    Uzal, Francisco A; McClane, Bruce A; Cheung, Jackie K; Theoret, James; Garcia, Jorge P; Moore, Robert J; Rood, Julian I

    2015-08-31

    The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. An in vivo model to study the anti-malaric capacity of plant extracts

    Directory of Open Access Journals (Sweden)

    Misael Chinchilla

    1998-03-01

    Full Text Available An in vivo model to study the antimalaric effect of plant extracts is described. White mice (25-30g body weight are treated subcutaneously with 0.6ml of the diluted extract starting seven days before P. berghei infection; treatment continues until death or for 30 days. Simultaneously 0.2ml of the extract are applied per os starting three days before infection. In a test of the model, treated and non-treated animals differed in body weight, survival time, haematocrite, parasitemia development, and spleen or liver weight of recent dead or killed mice.

  3. In Vivo Bioluminescence Imaging for the Study of Intestinal Colonization by Escherichia coli in Mice▿

    Science.gov (United States)

    Foucault, M.-L.; Thomas, L.; Goussard, S.; Branchini, B. R.; Grillot-Courvalin, C.

    2010-01-01

    Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of Escherichia coli harboring the genes for either the bacterial luciferase from Photorhabdus luminescens or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of Photinus pyralis (red and green thermostable P. pyralis luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (R2 = 0.98) or transcutaneously in the abdominal region of whole animals (R2 = 0.99) and the CFU counts in the feces of bacteria harboring the luxABCDE operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2ΩPamiluxABCDE), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of E. coli could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization. PMID:19880653

  4. In vivo bioluminescence imaging for the study of intestinal colonization by Escherichia coli in mice.

    Science.gov (United States)

    Foucault, M-L; Thomas, L; Goussard, S; Branchini, B R; Grillot-Courvalin, C

    2010-01-01

    Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of Escherichia coli harboring the genes for either the bacterial luciferase from Photorhabdus luminescens or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of Photinus pyralis (red and green thermostable P. pyralis luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (R2=0.98) or transcutaneously in the abdominal region of whole animals (R2=0.99) and the CFU counts in the feces of bacteria harboring the luxABCDE operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2OmegaPamiluxABCDE), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of E. coli could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization.

  5. Where are we in the study of animal emotions?

    Science.gov (United States)

    de Vere, Amber J; Kuczaj, Stan A

    2016-09-01

    The study of emotion is rife with debate over issues as fundamental as how to define emotion, and such disputes are particularly common in the nonhuman animal emotion literature. Here, we seek to address some of these issues, especially in terms of how they relate to animal research. Definitional issues are prevalent; clear definitions are often not given of crucial terms, including 'emotion,' and even where provided, such terms may be used inconsistently throughout a single paper. Further disagreement over the structure of emotions, and the nature of conscious experiences involved, leads to consistent differences in authors' criteria for emotions. We concur with those who believe that animals experience emotions and believe that animal emotions should be studied in their own right, not only as they compare to those of humans. We also propose several avenues for future research that we believe will further our understanding of animal emotions. First, the use of multiple measurement methods to assess emotional responses is most likely to provide the information necessary to distinguish between various states and opens the field to more research in harder-to-study species, such as marine mammals. Second, researchers should also endeavor to increase the range of emotions studied, particularly positive ones, in order to move toward a more balanced range of studied states. Finally, we believe that several aspects of personality research would prove beneficial to the study of animal emotions, particularly the distinction between trait and state emotion and the use of the rating method. WIREs Cogn Sci 2016, 7:354-362. doi: 10.1002/wcs.1399 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  6. Childhood Cruelty to Animals: A Tri-National Study

    Science.gov (United States)

    Mellor, David; Yeow, James; Hapidzal, Noor Fizlee Mohd; Yamamoto, Takashi; Yokoyama, Akimitsu; Nobuzane, Yosuke

    2009-01-01

    Childhood cruelty to animals is a symptom of conduct disorder that has been linked to the perpetration of violence in later life. Research has identified several factors associated with its etiology, including social factors. However, no cross-cultural studies on this phenomenon have been reported. This study investigated childhood cruelty to…

  7. Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study

    Science.gov (United States)

    Al-Oran, Sawsan Atallah; Hassuneh, Mona Rushdie; Al-Qaralleh, Haitham Naief; Rayyan, Walid Abu; Al-Thunibat, Osama Yosef; Mallah, Eyad; Abu-Rayyan, Ahmed; Salem, Shadi

    2017-01-01

    This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional) assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated. While in the immunomodulation assessment (functional), we investigated the effect of the extract on the proliferative capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The ingestion of M. peregrina extract caused a significant increase in the body weight, weight and number of cells of spleen and lymph nodes of the treated mice. Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV % were increased by the extract treatment in a dose-dependent manner. M. peregrina enhanced the proliferative responses of splenic lymphocytes for both T cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has revealed a T-cell dependent proliferation enhancement in the extract treated mice. Moreover, the oral administration of M. peregrina leaves extracts significantly increased PFCs/106 splenocytes in a dose-dependent manner. In conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg. PMID:29204086

  8. Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study

    Directory of Open Access Journals (Sweden)

    Ibrahim Salameh Al-Majali

    2017-10-01

    Full Text Available This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated. While in the immunomodulation assessment (functional, we investigated the effect of the extract on the proliferative capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The ingestion of M. peregrina extract caused a significant increase in the body weight, weight and number of cells of spleen and lymph nodes of the treated mice. Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV % were increased by the extract treatment in a dose-dependent manner. M. peregrina enhanced the proliferative responses of splenic lymphocytes for both T cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has revealed a T-cell dependent proliferation enhancement in the extract treated mice. Moreover, the oral administration of M. peregrina leaves extracts significantly increased PFCs/10 6 splenocytes in a dose-dependent manner. In conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg.

  9. Two-photon microscopy imaging of thy1GFP-M transgenic mice: a novel animal model to investigate brain dendritic cell subsets in vivo.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    Full Text Available Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype.With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity of dendritic cells (DCs, and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions.

  10. Two-Photon Microscopy Imaging of thy1GFP-M Transgenic Mice: A Novel Animal Model to Investigate Brain Dendritic Cell Subsets In Vivo

    Science.gov (United States)

    Laperchia, Claudia; Allegra Mascaro, Anna L.; Sacconi, Leonardo; Andrioli, Anna; Mattè, Alessandro; De Franceschi, Lucia; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Buffelli, Mario; Pavone, Francesco S.

    2013-01-01

    Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF) microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP) in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype. With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity) of dendritic cells (DCs), and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions. PMID:23409142

  11. Animal models to study cancer-initiating cells from glioblastoma.

    Science.gov (United States)

    Wee, Boyoung; Charles, Nikki; Holland, Eric C

    2011-06-01

    Three main subtypes of gliomas with distinct molecular pathologies have been modeled in animals to better understand their biology. Genetically engineered mouse models that take advantage of genetic abnormalities observed in human gliomas have been instrumental in this process. These models better recapitulate signaling transduction pathways and the microenvironment that play crucial roles in glioma formation than in vitro systems or transplantation models. An increasing amount of data supports the existence of cells functionally defined by their self-renewal ability and tumor-initiating potential upon serial transplantation. As the issue of these cells with stem cell character in gliomagenesis becomes more illusive, animal models that provide an accurate experimental system where the stem cell character can be manipulated and studied are urgently needed. This review provides an overview of the current state of the literature with respect to animal models used in the study of gliomas and cells with stem cell character in their native environment.

  12. Study on advancement of in vivo counting using mathematical simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kinase, Sakae [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2003-05-01

    To obtain an assessment of the committed effective dose, individual monitoring for the estimation of intakes of radionuclides is required. For individual monitoring of exposure to intakes of radionuclides, direct measurement of radionuclides in the body - in vivo counting- is very useful. To advance in a precision in vivo counting which fulfills the requirements of ICRP 1990 recommendations, some problems, such as the investigation of uncertainties in estimates of body burdens by in vivo counting, and the selection of the way to improve the precision, have been studied. In the present study, a calibration technique for in vivo counting application using Monte Carlo simulation was developed. The advantage of the technique is that counting efficiency can be obtained for various shapes and sizes that are very difficult to change for phantoms. To validate the calibration technique, the response functions and counting efficiencies of a whole-body counter installed in JAERI were evaluated using the simulation and measurements. Consequently, the calculations are in good agreement with the measurements. The method for the determination of counting efficiency curves as a function of energy was developed using the present technique and a physiques correction equation was derived from the relationship between parameters of correction factor and counting efficiencies of the JAERI whole-body counter. The uncertainties in body burdens of {sup 137}Cs estimated with the JAERI whole-body counter were also investigated using the Monte Carlo simulation and measurements. It was found that the uncertainties of body burdens estimated with the whole-body counter are strongly dependent on various sources of uncertainty such as radioactivity distribution within the body and counting statistics. Furthermore, the evaluation method of the peak efficiencies of a Ge semi-conductor detector was developed by Monte Carlo simulation for optimum arrangement of Ge semi-conductor detectors for

  13. Animal Models for the Study of Female Sexual Dysfunction

    Science.gov (United States)

    Marson, Lesley; Giamberardino, Maria Adele; Costantini, Raffaele; Czakanski, Peter; Wesselmann, Ursula

    2017-01-01

    Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain

  14. In vivo studies of peritendinous tissue in exercise

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, Henning; Skovgaard, D

    2000-01-01

    Soft tissue injury of tendons represents a major problem within sports medicine. Although several animal and cell culture studies have addressed this, human experiments have been limited in their ability to follow changes in specific tissue directly in response to interventions. Recently, methods...

  15. An Exploratory Study of Apache Middle School Students' Computer Animation.

    Science.gov (United States)

    Stokrocki, Mary; Buckpitt, Marcia

    The paper describes a participant observation study of a 3 week summer art program for Apache middle school students on the White Mountain Reservation. Computer art skills, specifically animation using a menu-driven computer paint program, were the focus of the investigation. Because it was in the context of a summer program, instruction was…

  16. Comparative Study of Biogas Yield Pattern in Some Animal and ...

    African Journals Online (AJOL)

    This research was a laboratory based work which compared Biogas yield patterns in some animal and household wastes. The parameters studied included dilution and concentration of substrates, the effect of available space in the digester, and the comparative biogas yield from different wastes. The method of research ...

  17. Field Research Studying Whales in an Undergraduate Animal Behavior Laboratory

    Science.gov (United States)

    MacLaren, R. David; Schulte, Dianna; Kennedy, Jen

    2012-01-01

    This work describes a new field research laboratory in an undergraduate animal behavior course involving the study of whale behavior, ecology and conservation in partnership with a non-profit research organization--the Blue Ocean Society for Marine Conservation (BOS). The project involves two weeks of training and five weekend trips on whale watch…

  18. EXPERIMENTAL STUDIES ON INFLAMMATION : II. EXPERIMENTAL CHEMICAL INFLAMMATION IN VIVO.

    Science.gov (United States)

    Wolf, E P

    1923-03-31

    1. None of the salts tested produce a marked inflammation in vivo in concentrations under 10 per cent. Potassium salts and the different citrates produced atypical inflammatory reactions in mice, but not in frogs. There was no true inflammation, however, characterized by blood vessel changes, migration of polymorphonuclear leucocytes and erythrocytes, and fluid exudation. 2. Synergistic action occurs when equal parts of strontium and magnesium salts are employed. There is a change in the appearance of the mesentery without a true inflammation, and this change does not occur with either salt alone. 3. Amino-acids and amines as a class do not produce inflammation, but histamine produces a marked inflammatory reaction in frogs and mice. 4. Tyramine does not cause an inflammatory reaction but has other marked effects; agglutination thrombi occur within the smaller blood vessels, both veins and arteries; in frogs there is a rapid clumping of the white blood cells followed by a true coagulation with strands of fibrin and entanglement of erythrocytes. This is very widespread and often kills the animal within an hour after injection. In mice it is the erythrocytes that clump and coagulation occurs very much later, usually at the end of 24 hours; still later there is complete absorption of the coagulated masses and the mesenteric circulation returns to normal. None of the mice died during the stage of clumping, and the clots never extended up the larger vessels as they did in the frogs. These effects are similar to the phenomena observed in the in vitro work, in which clumping of the cells appeared constantly. 5. Cantharidinum, histamine, and turpentine produced the most rapid and marked inflammation of any substances tried. These substances are all strongly positively chemotactic in vitro. The differences occurring when these substances are used in different species is a quantitative rather than a qualitative one, the body temperature being of some importance. Papain acted

  19. The functions of laminins: lessons from in vivo studies

    DEFF Research Database (Denmark)

    Ryan, M C; Christiano, A M; Engvall, E

    1996-01-01

    here. Instead, I will focus on the recent evidence gathered from gene knock out experiments in mice and from naturally occurring human and mouse gene mutations. The most obvious lesson from the above studies--other than demonstrating the importance of laminins in general--is that the structural......, through interactions with various receptors. It is interesting that the in vivo studies summarized above support both activities. In the case of laminin 5 mutations, the phenotypic consequence appears to be due primarily to the loss of an important structural link between the epithelial cytokeratins...

  20. Comparative Pharmaceutical Evaluation of Candesartan and Candesartan Cilexetil: Physicochemical Properties, In Vitro Dissolution and Ex Vivo In Vivo Studies.

    Science.gov (United States)

    Amer, Ahmed M; Allam, Ahmed N; Abdallah, Ossama Y

    2017-09-25

    The aim of the present work is to answer the question is it possible to replace the ester prodrug candesartan cilexetil (CC) by its active metabolite candesartan (C) to bypass the in vivo variable effect of esterase enzymes. A comparative physicochemical evaluation was conducted through solubility, dissolution, and stability studies; additionally, ex vivo permeation and in vivo studies were assessed. C demonstrated higher solubility over CC at alkaline pH. Moreover, dissolution testing using the pharmacopeial method showed better release profile of C even in the absence of surfactant in the testing medium. Both drugs demonstrated a slight degradation in acidic pH after short-term stability. Instead, shifting to alkaline pH of 6.5 and 7.4 showed superiority of C solution stability compared to CC solution. The ex vivo permeation results demonstrated that the parent compound C has a significant (P candesartan for clinical use similarly to azilsartan and its prodrug.

  1. Empirical analysis of BMD metrics in genetic toxicology part II: in vivo potency comparisons to promote reductions in the use of experimental animals for genetic toxicity assessment.

    Science.gov (United States)

    Wills, John W; Long, Alexandra S; Johnson, George E; Bemis, Jeffrey C; Dertinger, Stephen D; Slob, Wout; White, Paul A

    2016-05-01

    Genotoxicity tests have traditionally been used only for hazard identification, with qualitative dichotomous groupings being used to identify compounds that have the capacity to induce mutations and/or cytogenetic alterations. However, there is an increasing interest in employing quantitative analysis of in vivo dose-response data to derive point of departure (PoD) metrics that can be used to establish human exposure limits or margins of exposure (MOEs), thereby supporting human health risk assessments and regulatory decisions. This work is an extension of our companion article on in vitro dose-response analyses and outlines how the combined benchmark dose (BMD) approach across included covariates can be used to improve the analyses and interpretation of in vivo genetic toxicity dose-response data. Using the BMD-covariate approach, we show that empirical comparisons of micronucleus frequency dose-response data across multiple studies justifies dataset merging, with subsequent analyses improving the precision of BMD estimates and permitting attendant potency ranking of seven clastogens. Similarly, empirical comparisons of Pig-a mutant phenotype frequency data collected in males and females justified dataset merging across sex. This permitted more effective scrutiny regarding the effect of post-exposure sampling time on the mutagenicity of N-ethyl-N-nitrosourea observed in reticulocytes and erythrocytes in the Pig-a assay. The BMD-covariate approach revealed tissue-specific differences in the induction of lacZ transgene mutations in Muta™Mouse specimens exposed to benzo[a]pyrene (BaP), with the results permitting the formulation of mechanistic hypotheses regarding the observed potency ranking. Lastly, we illustrate how historical dose-response data for assessments that examined numerous doses (i.e. induced lacZ mutant frequency (MF) across 10 doses of BaP) can be used to improve the precision of BMDs derived from datasets with far fewer doses (i.e. lacZ MF for 3

  2. Pharmaco-EEG Studies in Animals: A History-Based Introduction to Contemporary Translational Applications.

    Science.gov (United States)

    Drinkenburg, Wilhelmus H I M; Ahnaou, Abdallah; Ruigt, Gé S F

    2015-01-01

    drugs on arousal and sleep architecture, assessing their neuropharmacological characteristics in vivo, including central exposure and information on kinetics. In view of the clear disadvantages as well as advantages of animal p-EEG as compared to clinical p-EEG, general statements about the usefulness of EEG as a biomarker to demonstrate the translatability of p-EEG effects should be made with caution, however, because they depend on the particular EEG or sleep parameter that is being studied. The contribution of animal p-EEG studies to the translational characterisation of centrally active drugs can be furthered by adherence to guidelines for methodological standardisation, which are presently under construction by the International Pharmaco-EEG Society (IPEG). © 2016 S. Karger AG, Basel.

  3. In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals.

    Science.gov (United States)

    Pinto, Suyene Rocha; Sarcinelle, Michelle Alvares; de Souza Albernaz, Marta; da Silva, Franciana Maria Rosa; Seabra, Sergio Henrique; Almeida do Nascimento, Patricia; Carvalho, Cosme Leonardo Gomes; Santos-Oliveira, Ralph

    2014-10-01

    The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Fluorescence Lifetime Imaging System for in Vivo Studies

    Directory of Open Access Journals (Sweden)

    Moinuddin Hassan

    2007-07-01

    Full Text Available In this article, a fluorescence lifetime imaging system for small animals is presented. Data were collected by scanning a region of interest with a measurement head, a linear fiber array with fixed separations between a single source fiber and several detection fibers. The goal was to localize tumors and monitor their progression using specific fluorescent markers. We chose a near-infrared contrast agent, Alexa Fluor 750 (Invitrogen Corp., Carlsbad, CA. Preliminary results show that the fluorescence lifetime for this dye was sensitive to the immediate environment of the fluorophore (in particular, pH, making it a promising candidate for reporting physiologic changes around a fluorophore. To quantify the intrinsic lifetime of deeply embedded fluorophores, we performed phantom experiments to investigate the contribution of photon migration effects on observed lifetime by calculating the fluorescence intensity decay time. A previously proposed theoretical model of migration, based on random walk theory, is also substantiated by new experimental data. The developed experimental system has been used for in vivo mouse imaging with Alexa Fluor 750 contrast agent conjugated to tumor-specific antibodies (trastuzumab [Herceptin]. Three-dimensional mapping of the fluorescence lifetime indicates lower lifetime values in superficial breast cancer tumors in mice.

  5. The use of transgenic animals to study lipoprotein metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, E.M.; Plump, A.S.

    1993-12-01

    The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.

  6. AN IN VIVO STUDY OF THE EFFECTS OF IONIZING RADIATION ON TISSUES BY LASER FLUORESCENCE SPECTROSCOPY

    Directory of Open Access Journals (Sweden)

    I. A. Guseva

    2016-01-01

    Full Text Available Background: Laser fluorescence spectroscopy (LFS is widely used in various medical areas, oncology being the most known of them. In general, the LFS is used for in vivo diagnostics of tumors. Recent studies have shown that this method could be used for diagnostics of local inflammation, induced by thermal or mechanical injury. It is of interest if LFS could be used for assessment of soft biological tissue injury caused by radiation exposure. Aim: To study fluorescence of an exogenous photosensitizer and its changes over time in the radiation injury area by LFS method in vivo. Materials and methods: The experiment was done in 12 outbred SHK mice whose right hind limbs were irradiated using a gamma-therapy device ROKUS-AM (source, 60Co, at dose of 15 Gy. Before irradiation, the photosensitizer Photosens was administered to all animals intraperitoneally at dose of 2.5 mg/kg. For 21 days fluorescence was assessed in vivo with a laser diagnostic system LAKK-M in the “fluorescence” operation mode, with an excitation wavelength of 635 nm. At days 7 and 21, tissue samples from the irradiated areas of the model animals were studied histologically and differential blood cell counts were assessed simultaneously. Results: The LFS method showed an increase in the accumulation of the photosensitizer in the affected area, compared to an intact contralateral area, with higher signal intensity from the irradiated limb. The changes in the fluorescence signal from the affected over time had two characteristic peaks at days 3 and 14, probably reflecting the stage of local radiation injury. Conclusion: The use of LFS with an exogenous photosensitizer has a potential for a personalized assessment of radiation reactions in radiology.

  7. Evaluation of the potential of Mycobacterium smegmatis as vaccine Candidate against tuberculosis by in silico and in vivo studies

    Directory of Open Access Journals (Sweden)

    Le Thuy Nguyen Thi

    2010-04-01

    Full Text Available In this study, we scanned multiple published databases of gene expression in vivo of M. tuberculosis at different phases of infection in animals and humans, to select 38 proteins that are highly expressed in the active, latent and reactivation phases. The selected proteins were predicted for T and B epitopes. For each proteins, the regions containing T and B epitopes were selected at the same time to look for identical epitopes on M. smegmatis based on sequence alignments. Preliminary studies of humoral immunogenicity and cross-reactivity with M. tuberculosis in mice using two M. smegmatis-derived experimental vaccines were carried out, demonstrating the immunogenicity of M. smegmatis proteoliposomes and the recognition of M. tuberculosis proteins by the sera of animals immunized with this vaccine candidate. The conjunction of in silico and in vivo studies suggested the potential for future evaluation of M. smegmatis as vaccine candidate against tuberculosis using different strategies

  8. A retrospective study on incidence of lameness in domestic animals

    OpenAIRE

    A. Mohsina; M. M. S Zama; P. Tamilmahan; M. B. Gugjoo; Singh, K.; Gopinathan, A; Gopi, M; Karthik, K.

    2014-01-01

    Aim: To study the incidence of lameness among different species of animals presented to the Veterinary Polyclinic, Indian Veterinary Research Institute, Izatnagar. Materials and Methods: Outpatient department (OPD) records for the period from January 2006 to December 2010 were referred and information was collected regarding number of lameness in different species, breeds, type of injury, limb affected, gender, age at onset, treatment offered, outcome and any reoccurrence. In this study, f...

  9. Acute pressure changes in the brain are correlated with MR elastography stiffness measurements: initial feasibility in an in vivo large animal model.

    Science.gov (United States)

    Arani, Arvin; Min, Hoon-Ki; Fattahi, Nikoo; Wetjen, Nicholas M; Trzasko, Joshua D; Manduca, Armando; Jack, Clifford R; Lee, Kendall H; Ehman, Richard L; Huston, John

    2018-02-01

    The homeostasis of intracranial pressure (ICP) is of paramount importance for maintaining normal brain function. A noninvasive technique capable of making direct measurements of ICP currently does not exist. MR elastography (MRE) is capable of noninvasively measuring brain tissue stiffness in vivo, and may act as a surrogate to measure ICP. The objective of this study was to investigate the impact of changing ICP on brain stiffness using MRE in a swine model. Baseline MRE measurements were obtained, and then catheters were surgically placed into the left and right lateral ventricles of three animals. ICP was systematically increased over the range of 0 to 55 millimeters mercury (mmHg), and stiffness measurements were made using brain MRE at vibration frequencies of 60 hertz (Hz), 90 Hz, 120 Hz, and 150 Hz. A significant linear correlation between stiffness and ICP in the cross-subject comparison was observed for all tested vibrational frequencies (P ≤ 0.01). The 120 Hz (0.030 ± 0.004 kilopascal (kPa)/mmHg, P Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  10. An ex vivo culture system to study thyroid development.

    Science.gov (United States)

    Delmarcelle, Anne-Sophie; Villacorte, Mylah; Hick, Anne-Christine; Pierreux, Christophe E

    2014-06-06

    The thyroid is a bilobated endocrine gland localized at the base of the neck, producing the thyroid hormones T3, T4, and calcitonin. T3 and T4 are produced by differentiated thyrocytes, organized in closed spheres called follicles, while calcitonin is synthesized by C-cells, interspersed in between the follicles and a dense network of blood capillaries. Although adult thyroid architecture and functions have been extensively described and studied, the formation of the "angio-follicular" units, the distribution of C-cells in the parenchyma and the paracrine communications between epithelial and endothelial cells is far from being understood. This method describes the sequential steps of mouse embryonic thyroid anlagen dissection and its culture on semiporous filters or on microscopy plastic slides. Within a period of four days, this culture system faithfully recapitulates in vivo thyroid development. Indeed, (i) bilobation of the organ occurs (for e12.5 explants), (ii) thyrocytes precursors organize into follicles and polarize, (iii) thyrocytes and C-cells differentiate, and (iv) endothelial cells present in the microdissected tissue proliferate, migrate into the thyroid lobes, and closely associate with the epithelial cells, as they do in vivo. Thyroid tissues can be obtained from wild type, knockout or fluorescent transgenic embryos. Moreover, explants culture can be manipulated by addition of inhibitors, blocking antibodies, growth factors, or even cells or conditioned medium. Ex vivo development can be analyzed in real-time, or at any time of the culture by immunostaining and RT-qPCR. In conclusion, thyroid explant culture combined with downstream whole-mount or on sections imaging and gene expression profiling provides a powerful system for manipulating and studying morphogenetic and differentiation events of thyroid organogenesis.

  11. Immunotoxicology of arc welding fume: worker and experimental animal studies.

    Science.gov (United States)

    Zeidler-Erdely, Patti C; Erdely, Aaron; Antonini, James M

    2012-01-01

    Arc welding processes generate complex aerosols composed of potentially hazardous metal fumes and gases. Millions of workers worldwide are exposed to welding aerosols daily. A health effect of welding that is of concern to the occupational health community is the development of immune system dysfunction. Increased severity, frequency, and duration of upper and lower respiratory tract infections have been reported among welders. Specifically, multiple studies have observed an excess mortality from pneumonia in welders and workers exposed to metal fumes. Although several welder cohort and experimental animal studies investigating the adverse effects of welding fume exposure on immune function have been performed, the potential mechanisms responsible for these effects are limited. The objective of this report was to review both human and animal studies that have examined the effect of welding fume pulmonary exposure on local and systemic immune responses.

  12. Immunotoxicology of arc welding fume: Worker and experimental animal studies

    Science.gov (United States)

    Zeidler-Erdely, Patti C.; Erdely, Aaron; Antonini, James M.

    2015-01-01

    Arc welding processes generate complex aerosols composed of potentially hazardous metal fumes and gases. Millions of workers worldwide are exposed to welding aerosols daily. A health effect of welding that is of concern to the occupational health community is the development of immune system dysfunction. Increased severity, frequency, and duration of upper and lower respiratory tract infections have been reported among welders. Specifically, multiple studies have observed an excess mortality from pneumonia in welders and workers exposed to metal fumes. Although several welder cohort and experimental animal studies investigating the adverse effects of welding fume exposure on immune function have been performed, the potential mechanisms responsible for these effects are limited. The objective of this report was to review both human and animal studies that have examined the effect of welding fume pulmonary exposure on local and systemic immune responses. PMID:22734811

  13. STUDY OF THE TOXIC EFFECTS OF CYPERMETHRIN IN EXPERIMENTAL ANIMALS

    Directory of Open Access Journals (Sweden)

    Syed Mehmood Hasan

    2016-06-01

    Full Text Available This study focuses on the toxic effects of a commercially available pesticide, cypermethrin (CM, on animals. This pesticide was administered in the form of aerosol spray through a nebulizer. The study was performed in four different groups and a constant dose of the pesticide was administered once, twice, thrice and four times a day to the respective group for a period of 30 days. The animals were then dissected to study the pesticide effects on different organs. The organs were preserved in 10% formalin. The tissues were processed by basic histopathological method and the slides were prepared for observation. The results were recorded on a performa and were quantified by a unique scoring system. It is concluded that the injurious effects to the mentioned organs were dose and frequency dependent.

  14. Social Information Transmission in Animals: Lessons from Studies of Diffusion.

    Science.gov (United States)

    Duboscq, Julie; Romano, Valéria; MacIntosh, Andrew; Sueur, Cédric

    2016-01-01

    The capacity to use information provided by others to guide behavior is a widespread phenomenon in animal societies. A standard paradigm to test if and/or how animals use and transfer social information is through social diffusion experiments, by which researchers observe how information spreads within a group, sometimes by seeding new behavior in the population. In this article, we review the context, methodology and products of such social diffusion experiments. Our major focus is the transmission of information from an individual (or group thereof) to another, and the factors that can enhance or, more interestingly, inhibit it. We therefore also discuss reasons why social transmission sometimes does not occur despite being expected to. We span a full range of mechanisms and processes, from the nature of social information itself and the cognitive abilities of various species, to the idea of social competency and the constraints imposed by the social networks in which animals are embedded. We ultimately aim at a broad reflection on practical and theoretical issues arising when studying how social information spreads within animal groups.

  15. Multigram Synthesis and in Vivo Efficacy Studies of a Novel Multitarget Anti-Alzheimer’s Compound

    Directory of Open Access Journals (Sweden)

    Irene Sola

    2015-03-01

    Full Text Available We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer’s disease (AD. Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aβ42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aβ42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aβ peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aβ lowering effect in vivo might be related to its lower in vitro potency toward Aβ aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio.

  16. Studies on the in vivo biotransformation of the tobacco alkaloid beta-nicotyrine.

    Science.gov (United States)

    Liu, X; Castagnoli, K; Van Der Schyf, C J; Castagnoli, N

    2000-05-01

    This paper reports the results of studies on the in vivo metabolic fate of the tobacco alkaloid 1-methyl-2-(3-pyridinyl)pyrrole (beta-nicotyrine) in New Zealand white rabbits. Two previously characterized metabolites, 5-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (5-hydroxycotinine) and 2-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one, were present in low concentrations in the urine of the treated animals. The major urinary metabolite of beta-nicotyrine was identified as cis-3'-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (cis-3'-hydroxycotinine), the diastereoisomer of the major urinary metabolite of (S)-nicotine. The pathway leading to cis-3'-hydroxycotinine is proposed to proceed via autoxidation of 2-hydroxy-1-methyl-5-(3-pyridinyl)pyrrole, a postulated cytochrome P450-generated metabolite of beta-nicotyrine, followed by reduction of the carbon-carbon double bond present in the resulting 3-hydroxy-3-pyrrolin-2-one species. This proposal is supported by the in vivo biotransformation of 2-acetoxy-1-methyl-5-(3-pyridinyl)pyrrole, a latent form of the putative hydroxypyrrole intermediate, to cis-3'-hydroxycotinine. The in vivo conversion of 5-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one to 5-hydroxycotinine is offered as evidence that supports the proposed reduction step.

  17. Free radicals induced by sunlight in different spectral regions - in vivo versus ex vivo study.

    Science.gov (United States)

    Lohan, Silke B; Müller, Robert; Albrecht, Stephanie; Mink, Kathrin; Tscherch, Kathrin; Ismaeel, Fakher; Lademann, Jürgen; Rohn, Sascha; Meinke, Martina C

    2016-05-01

    Sunlight represents an exogenous factor stimulating formation of free radicals which can induce cell damage. To assess the effect of the different spectral solar regions on the development of free radicals in skin, in vivo electron paramagnetic resonance (EPR) investigations with human volunteers and ex vivo studies on excised human and porcine skin were carried out. For all skin probes, the ultraviolet (UV) spectral region stimulates the most intensive radical formation, followed by the visible (VIS) and the near infrared (NIR) regions. A comparison between the different skin models shows that for UV light, the fastest and highest production of free radicals could be detected in vivo, followed by excised porcine and human skin. The same distribution pattern was found for the VIS/NIR spectral regions, whereby the differences in radical formation between in vivo and ex vivo were less pronounced. An analysis of lipid composition in vivo before and after exposure to UV light clearly showed modifications in several skin lipid components; a decrease of ceramide subclass [AP2] and an increase of ceramide subclass [NP2], sodium cholesterol sulphate and squalene (SQ) were detectable. In contrast, VIS/NIR irradiation led to an increase of ceramides [AP2] and SCS, and a decrease of SQ. These results, which are largely comparable for the different skin models investigated in vivo and ex vivo, indicate that radiation exposure in different spectral regions strongly influences radical production in skin and also results in changes in skin lipid composition, which is essential for barrier function. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Gambling disorder: an integrative review of animal and human studies.

    Science.gov (United States)

    Nautiyal, Katherine M; Okuda, Mayumi; Hen, Rene; Blanco, Carlos

    2017-04-01

    Gambling disorder (GD), previously called pathological gambling and classified as an impulse control disorder in DSM-III and DSM-IV, has recently been reclassified as an addictive disorder in the DSM-5. It is widely recognized as an important public health problem associated with substantial personal and social costs, high rates of psychiatric comorbidity, poor physical health, and elevated suicide rates. A number of risk factors have been identified, including some genetic polymorphisms. Animal models have been developed in order to study the underlying neural basis of GD. Here, we discuss recent advances in our understanding of the risk factors, disease course, and pathophysiology. A focus on a phenotype-based dissection of the disorder is included in which known neural correlates from animal and human studies are reviewed. Finally, current treatment approaches are discussed, as well as future directions for GD research. © 2017 New York Academy of Sciences.

  19. Photoacoustic analysis of thyroid cancer in vivo: a pilot study

    Science.gov (United States)

    Kim, Jeesu; Kim, Min-Hee; Jo, Kwanhoon; Ha, Jeonghoon; Kim, Yongmin; Lim, Dong-Jun; Kim, Chulhong

    2017-03-01

    Thyroid cancer is one of the most prevalent cancers. About 3-8% of the people in the United States have thyroid nodules, and 5-15% of these nodules are malignant. Fine-needle aspiration biopsy (FNAB) is a standard procedure to diagnose malignity of nodules. However, about 10-20% of FNABs produce indeterminable results, which leads to repeat biopsies and unnecessary surgical operations. We have explored photoacoustic (PA) imaging as a new method to identify cancerous nodules. In a pilot study to test its feasibility, we recruited patients with thyroid nodules (currently 36 cases with 21 malignant and 15 benign nodules), acquired in vivo PA and ultrasound (US) images of the nodules in real time using a recently-developed clinical PA/US imaging system, and analyzed the acquired data offline. The preliminary results show that malignant and benign nodules could be differentiated by utilizing their PA amplitudes at different excitation wavelengths. This is the first in vivo PA analysis of thyroid nodules. Although a larger-scale study is needed for statistical significance, the preliminary results show the good potential of PA imaging as a non-invasive tool for triaging thyroid cancer.

  20. Influence of intestinal bacteria, sex of the animal, and position of the nitro group on the hepatic genotoxicity of nitrotoluene isomers in vivo.

    Science.gov (United States)

    Doolittle, D J; Sherrill, J M; Butterworth, B E

    1983-06-01

    The nitrotoluenes failed to induce unscheduled DNA synthesis in in vitro cultures of rat hepatocytes. Because intestinal bacteria are known to be involved in the metabolic activation of other nitroaromatic compounds, the genotoxicity of the nitrotoluenes was evaluated using an in vivo-in vitro hepatocyte DNA repair assay. 2-Nitrotoluene (2NT), 3-nitrotoluene, or 4-nitrotoluene was administered by gavage to male F344 rats. At selected times after treatment, primary hepatocyte cultures were prepared and incubated with [3H]thymidine, and unscheduled DNA synthesis was assessed by quantitative autoradiography. Corn oil controls ranged from -6 to -3 net grains/nucleus (NG). Only 2NT at 12 hr after treatment induced DNA repair (200 mg/kg: 15.4 NG). Twenty-four hr following treatment with 2NT, a 50-fold increase in the number of hepatocytes in S phase was observed and indicated that 2NT induces cell division in addition to DNA repair. To examine the influence of intestinal bacteria on the hepatic genotoxicity of 2NT, germ-free rats and germ-free rats inoculated with Charles River Altered Schaedler Flora were gavaged with 2NT. The cecal bacterial status was confirmed at sacrifice. 2NT did not induce DNA repair in germ-free animals (200 mg/kg: -3.8 NG), whereas DNA repair was induced in Charles River Altered Schaedler Flora-associated animals (200 mg/kg: 5.4 NG). When F344 females with conventional intestinal microflora were gavaged with 2NT and primary hepatocyte cultures were prepared, no unscheduled DNA synthesis was observed (200 mg/kg: -2.6 NG). Male and female F344 rats were shown to have similar populations of intestinal bacteria. These results demonstrate that the mononitrotoluenes display marked isomeric differences in their genotoxic potential, indicate the obligatory role of intestinal bacteria in the metabolic activation of 2NT, and show that the genotoxic potential of 2NT is dependent upon the sex of the animal under study.

  1. In vivo studies of peritendinous tissue in exercise

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, Henning; Skovgaard, D

    2000-01-01

    Soft tissue injury of tendons represents a major problem within sports medicine. Although several animal and cell culture studies have addressed this, human experiments have been limited in their ability to follow changes in specific tissue directly in response to interventions. Recently, methods...... exercise. This coincides with a surprisingly marked drop in tissue pressure during contraction. With regards to both circulation, metabolism and collagen formation, peritendinous tissue represents a dynamic, responsive region that adapts markedly to acute muscular activity....

  2. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    Science.gov (United States)

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  3. Study of in vivo catheter biofilm infections using pediatric central venous catheter implanted in rat.

    Science.gov (United States)

    Chauhan, Ashwini; Ghigo, Jean-Marc; Beloin, Christophe

    2016-03-01

    Venous access catheters used in clinics are prone to biofilm contamination, contributing to chronic and nosocomial infections. Although several animal models for studying device-associated biofilms were previously described, only a few detailed protocols are currently available. Here we provide a protocol using totally implantable venous access ports (TIVAPs) implanted in rats. This model recapitulates all phenomena observed in the clinic, and it allows bacterial biofilm development and physiology to be studied. After TIVAP implantation and inoculation with luminescent pathogens, in vivo biofilm formation can be monitored in situ, and biofilm biomass can be recovered from contaminated TIVAP and organs. We used this protocol to study host responses to biofilm infection, to evaluate preventive and curative antibiofilm strategies and to study fundamental biofilm properties. For this procedure, one should expect ∼3 h of hands-on time, including the implantation in one rat followed by in situ luminescence monitoring and bacterial load estimation.

  4. Animal Testing

    Science.gov (United States)

    Moretto, Johnny; Chauffert, Bruno; Bouyer, Florence

    The development of a new anticancer drug is a long, complex and multistep process which is supervised by regulatory authorities from the different countries all around the world [1]. Application of a new drug for admission to the market is supported by preclinical and clinical data, both including the determination of pharmacodynamics, toxicity, antitumour activity, therapeutic index, etc. As preclinical studies are associated with high cost, optimization of animal experiments is crucial for the overall development of a new anticancer agent. Moreover, in vivo efficacy studies remain a determinant panel for advancement of agents to human trials and thus, require cautious design and interpretation from experimental and ethical point of views.

  5. Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo.

    Science.gov (United States)

    Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

    2015-05-07

    The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ∼21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.

  6. Immunology and Homeopathy. 3. Experimental Studies on Animal Models

    Directory of Open Access Journals (Sweden)

    Paolo Bellavite

    2006-01-01

    Full Text Available A search of the literature and the experiments carried out by the authors of this review show that there are a number of animal models where the effect of homeopathic dilutions or the principles of homeopathic medicine have been tested. The results relate to the immunostimulation by ultralow doses of antigens, the immunological models of the ‘simile’, the regulation of acute or chronic inflammatory processes and the use of homeopathic medicines in farming. The models utilized by different research groups are extremely etherogeneous and differ as the test medicines, the dilutions and the outcomes are concerned. Some experimental lines, particularly those utilizing mice models of immunomodulation and anti-inflammatory effects of homeopathic complex formulations, give support to a real effect of homeopathic high dilutions in animals, but often these data are of preliminary nature and have not been independently replicated. The evidence emerging from animal models is supporting the traditional ‘simile’ rule, according to which ultralow doses of compounds, that in high doses are pathogenic, may have paradoxically a protective or curative effect. Despite a few encouraging observational studies, the effectiveness of the homeopathic prevention or therapy of infections in veterinary medicine is not sufficiently supported by randomized and controlled trials.

  7. Impact of food intake on in vivo VOC concentrations in exhaled breath assessed in a caprine animal model.

    Science.gov (United States)

    Fischer, Sina; Bergmann, Andreas; Steffens, Markus; Trefz, Phillip; Ziller, Mario; Miekisch, Wolfram; Schubert, Jochen S; Köhler, Heike; Reinhold, Petra

    2015-12-15

    Physiological processes within the body may change emitted volatile organic compound (VOC) composition, and may therefore cause confounding biological background variability in breath gas analyses. To evaluate the effect of food intake on VOC concentration patterns in exhaled breath, this study assessed the variability of VOC concentrations due to food intake in a standardized caprine animal model. VOCs in (i) alveolar breath gas samples of nine clinically healthy goats and (ii) room air samples were collected and pre-concentrated before morning feeding and repeatedly after (+60 min, +150 min, +240 min) using needle trap microextraction (NTME). Analysis of VOCs was performed by gas chromatography and mass spectrometry (GC-MS). Only VOCs with significantly higher concentrations in breath gas samples compared to room air samples were taken into consideration. Six VOCs that belonged to the chemical classes of hydrocarbons and alcohols were identified presenting significantly different concentrations before and after feeding. Selected hydrocarbons showed a concentration pattern that was characterized by an initial increase 60 min after food intake, and a subsequent gradual decrease. Results emphasize consideration of physiological effects on exhaled VOC concentrations due to food intake with respect to standardized protocols of sample collection and critical evaluation of results.

  8. Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: a review.

    Science.gov (United States)

    García, Y; Díaz-Castro, J

    2013-10-01

    Iron deficiency is the most common nutritional deficiency in the world. Special molecules have evolved for iron acquisition, transport and storage in soluble, nontoxic forms. Studies about the effects of iron on health are focused on iron metabolism or nutrition to prevent or treat iron deficiency and anemia. These studies are focused in two main aspects: (1) basic studies to elucidate iron metabolism and (2) nutritional studies to evaluate the efficacy of iron supplementation to prevent or treat iron deficiency and anemia. This paper reviews the advantages and disadvantages of the experimental models commonly used as well as the methods that are more used in studies related to iron. In vitro studies have used different parts of the gut. In vivo studies are done in humans and animals such as mice, rats, pigs and monkeys. Iron metabolism is a complex process that includes interactions at the systemic level. In vitro studies, despite physiological differences to humans, are useful to increase knowledge related to this essential micronutrient. Isotopic techniques are the most recommended in studies related to iron, but their high cost and required logistic, making them difficult to use. The depletion-repletion of hemoglobin is a method commonly used in animal studies. Three depletion-repletion techniques are mostly used: hemoglobin regeneration efficiency, relative biological values (RBV) and metabolic balance, which are official methods of the association of official analytical chemists. These techniques are well-validated to be used as studies related to iron and their results can be extrapolated to humans. Knowledge about the main advantages and disadvantages of the in vitro and animal models, and methods used in these studies, could increase confidence of researchers in the experimental results with less costs.

  9. Estrogens and atherosclerosis: insights from animal models and cell systems

    National Research Council Canada - National Science Library

    Nofer, Jerzy-Roch

    2012-01-01

    .... The development of atherosclerotic lesions involves complex interplay between various pro- or anti-atherogenic processes that can be effectively studied only in vivo in appropriate animal models...

  10. 5-Nitro-2-furyl derivative actives against Trypanosoma cruzi: preliminary in vivo studies.

    Science.gov (United States)

    Cabrera, Eliana; Murguiondo, Mariana González; Arias, Marelina González; Arredondo, Carolina; Pintos, Cristina; Aguirre, Gabriela; Fernández, Marcelo; Basmadjián, Yester; Rosa, Raquel; Pacheco, José Pedro; Raymondo, Stella; Di Maio, Rossanna; González, Mercedes; Cerecetto, Hugo

    2009-10-01

    Ten 5-nitro-2-furyl derivatives, with good to excellent in vitro anti-Trypanosoma cruzi activity, and nifurtimox were tested oral and intraperitoneally on healthy animals for its acute toxicity on murine models. According to animals' survival percentage, organ histological results, biochemical and haematological findings, three new derivatives, with toxicity like nifurtimox, were selected to test in vivo as antichagasic agents. Clearly, dependences between chemical structure and both acute toxicity and in vivo anti-T. cruzi activity were observed. 4-Hexyl-1-[3-(5-nitro-2-furyl)-2-propenylidene]semicarbazide displayed good profile as anti-T. cruzi agent and better acute toxicity profile than nifurtimox.

  11. In vitro and in vivo studies on biodegradable magnesium alloy

    Directory of Open Access Journals (Sweden)

    Lida Hou

    2014-10-01

    Full Text Available The microstructure, mechanical property, electrochemical behavior and biocompatibility of magnesium alloy (BioDe MSM™ were studied in the present work. The experimental results demonstrated that grain refining induced by extrusion improves the alloy strength significantly from 162 MPa for the as-cast alloy to 241 MPa for the as-extruded one. The anticorrosion properties of the as-extruded alloy also increased. Furthermore, the hemolysis ratio was decreased from 4.7% for the as-cast alloy to 2.9% for the as-extruded one, both below 5%. BioDe MSM™ alloy shows good biocompatibility after being implanted into the dorsal muscle and the femoral shaft of the New Zealand rabbit, respectively, and there are no abnormalities after short-term implantation. In vivo observation indicated that the corrosion rate of this alloy varies with different implantation positions, with higher degradation rate in the femur than in the muscle.

  12. How Can We Study the Evolution of Animal Minds?

    Science.gov (United States)

    Cauchoix, Maxime; Chaine, Alexis S.

    2016-01-01

    During the last 50 years, comparative cognition and neurosciences have improved our understanding of animal minds while evolutionary ecology has revealed how selection acts on traits through evolutionary time. We describe how cognition can be subject to natural selection like any other biological trait and how this evolutionary approach can be used to understand the evolution of animal cognition. We recount how comparative and fitness methods have been used to understand the evolution of cognition and outline how these approaches could extend our understanding of cognition. The fitness approach, in particular, offers unprecedented opportunities to study the evolutionary mechanisms responsible for variation in cognition within species and could allow us to investigate both proximate (i.e., neural and developmental) and ultimate (i.e., ecological and evolutionary) underpinnings of animal cognition together. We highlight recent studies that have successfully shown that cognitive traits can be under selection, in particular by linking individual variation in cognition to fitness. To bridge the gap between cognitive variation and fitness consequences and to better understand why and how selection can occur on cognition, we end this review by proposing a more integrative approach to study contemporary selection on cognitive traits combining socio-ecological data, minimally invasive neuroscience methods and measurement of ecologically relevant behaviors linked to fitness. Our overall goal in this review is to build a bridge between cognitive neuroscientists and evolutionary biologists, illustrate how their research could be complementary, and encourage evolutionary ecologists to include explicit attention to cognitive processes in their studies of behavior. PMID:27014163

  13. Mineral imbalances in farm animals and their study and diagnosis with isotopic tracers.

    Science.gov (United States)

    Underwood, E J

    1976-12-01

    Twenty-two mineral elements are known to be essential for animal life. These are calcium, phosphorus, sulphur, potassium, sodium, chlorine, magnesium, iron, iodine, copper, manganese, zinc, cobalt, molybdenum, selenium, chromium, tin, vanadium, fluorine, silicon, nickel and arsenic. Naturally occurring and man-made dietary imbalances of many of these elements and their interactions with other minerals are described and their functions and requirements by farm animals are outlined. The nature and importance of metabolic interactions among the mineral elements are discussed and the important concept stressed that there is no single minimum requirement or safe tolerance of a particular mineral, but a series of such minimum requirements and safe tolerances depending on the extent to which other minerals with which it interacts is present or absent from the diet. Radioactive tracer elements are shown to be of great value in the determination of mineral nutrient availability to the animal and for following mineral metabolic movements in the body. They are also shown to have considerable potential for the diagnosis of mineral imbalances. Various in vivo and in vitro techniques, involving both radioactive and stable tracers developed for the early diagnosis of mineral deficiencies are described and the strengths and weaknesses of such techniques in comparison with standard biochemical tests, are discussed. The need for further critical studies with isotopic tracers in the detection and diagnosis of mineral imbalances is emphasized. The main types of biochemical criteria used in the diagnosis of mineral deficiencies and excesses are given, with appropriate examples of their use.

  14. In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using Shear Wave Elastography, Histology and 2 Photon Excitation Microscopy: Insight from an Animal Model.

    Directory of Open Access Journals (Sweden)

    Laura Peralta

    Full Text Available Prematurity affects 11% of the births and is the main cause of infant mortality. On the opposite case, the failure of induction of parturition in the case of delayed spontaneous birth is associated with fetal suffering. Both conditions are associated with precocious and/or delayed cervical ripening. Quantitative and objective information about the temporal evolution of the cervical ripening may provide a complementary method to identify cases at risk of preterm delivery and to assess the likelihood of successful induction of labour. In this study, the cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave Elastography (SWE. This technique assesses the stiffness of tissue through the measurement of shear waves speed (SWS. In the present study, 9 pregnant ewes were used. Cervical ripening was induced at 127 days of pregnancy (term: 145 days by dexamethasone injection in 5 animals, while 4 animals were used as control. Elastographic images of the cervix were obtained by two independent operators every 4 hours during 24 hours after injection to monitor the cervical maturation induced by the dexamethasone. Based on the measurements of SWS during vaginal ultrasound examination, the stiffness in the second ring of the cervix was quantified over a circular region of interest of 5 mm diameter. SWS was found to decrease significantly in the first 4-8 hours after dexamethasone compared to controls, which was associated with cervical ripening induced by dexamethasone (from 1.779 m/s ± 0.548 m/s, p < 0.0005, to 1.291 m/s ± 0.516 m/s, p < 0.000. Consequently a drop in the cervical elasticity was quantified too (from 9.5 kPa ± 0.9 kPa, p < 0.0005, to 5.0 kPa ± 0.8 kPa, p < 0.000. Moreover, SWE measurements were highly reproducible between both operators at all times. Cervical ripening induced by dexamethasone was confirmed by the significant increase in maternal plasma Prostaglandin E2 (PGE2, as evidenced by the assay of its

  15. Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges.

    Science.gov (United States)

    Chapman, Kathryn; Adjei, Akosua; Baldrick, Paul; da Silva, Antonio; De Smet, Karen; DiCicco, Richard; Hong, Seung Suh; Jones, David; Leach, Michael W; McBlane, James; Ragan, Ian; Reddy, Praveen; Stewart, Donald I H; Suitters, Amanda; Sims, Jennifer

    2016-01-01

    Biosimilars are biological medicinal products that contain a version of the active substance of an already authorised original biological medicinal product (the innovator or reference product). The first approved biosimilar medicines were small proteins, and more recently biosimilar versions of innovator monoclonal antibody (mAb) drugs have entered development as patents on these more complex proteins expire. In September 2013, the first biosimilar mAb, infliximab, was authorised in Europe. In March 2015, the first biosimilar (Zarxio™, filgrastim-sndz, Sandoz) was approved by the US Food and Drug Administration; however, to date no mAb biosimilars have been approved in the US. There are currently major differences between how biosimilars are regulated in different parts of the world, leading to substantial variability in the amount of in vivo nonclinical toxicity testing required to support clinical development and marketing of biosimilars. There are approximately 30 national and international guidelines on biosimilar development and this number is growing. The European Union's guidance describes an approach that enables biosimilars to enter clinical trials based on robust in vitro data alone; in contrast, the World Health Organization's guidance is interpreted globally to mean in vivo toxicity studies are mandatory. We reviewed our own experience working in the global regulatory environment, surveyed current practice, determined drivers for nonclinical in vivo studies with biosimilar mAbs and shared data on practice and study design for 25 marketed and as yet unmarketed biosimilar mAbs that have been in development in the past 5y. These data showed a variety of nonclinical in vivo approaches, and also demonstrated the practical challenges faced in obtaining regulatory approval for clinical trials based on in vitro data alone. The majority of reasons for carrying out nonclinical in vivo studies were not based on scientific rationale, and therefore the authors

  16. Pain assessment in animal models: do we need further studies?

    Directory of Open Access Journals (Sweden)

    Gigliuto C

    2014-05-01

    Full Text Available Carmelo Gigliuto,1 Manuela De Gregori,2 Valentina Malafoglia,3 William Raffaeli,3 Christian Compagnone,4 Livia Visai,5,6 Paola Petrini,7 Maria Antonietta Avanzini,9 Carolina Muscoli,8 Jacopo Viganò,11 Francesco Calabrese,11 Tommaso Dominioni,11 Massimo Allegri,2,10 Lorenzo Cobianchi111Anaesthesia and Intensive Care, University of Pavia, Pavia, 2Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 3ISAL Foundation, Institute for Research on Pain, Torre Pedrera, Rimini, 4Department of Anaesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, 5Department of Molecular Medicine, Center for Tissue Engineering (CIT, INSTM UdR of Pavia, University of Pavia, Pavia, 6Department of Occupational Medicine, Ergonomy and Disability, Laboratory of Nanotechnology, Salvatore Maugeri Foundation, IRCCS, Veruno, 7Dipartimento di Chimica, Materiali e Ingegneria Chimica 'G Natta' and Unità di Ricerca Consorzio INSTM, Politecnico di Milano, Milan, 8Department of Health Science, University Magna Grecia of Catanzaro and Centro del Farmaco, IRCCS San Raffaele Pisana, Roma, 9Laboratory of Transplant Immunology/Cell Factory, Fondazione IRCCS Policlinico "San Matteo", Pavia, 10Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, 11University of Pavia, Department of Surgical, Clinical, Paediatric and Diagnostic Science, General Surgery 1, IRCCS Fondazione Policlinico San Matteo, Pavia, ItalyAbstract: In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus

  17. Renal denervation by intravascular ultrasound: Preliminary in vivo study

    Science.gov (United States)

    Sinelnikov, Yegor; McClain, Steve; Zou, Yong; Smith, David; Warnking, Reinhard

    2012-10-01

    Ultrasound denervation has recently become a subject of intense research in connection with the treatment of complex medical conditions including neurological conditions, development of pain management, reproduction of skin sensation, neuropathic pain and spasticity. The objective of this study is to investigate the use of intravascular ultrasound to produce nerve damage in renal sympathetic nerves without significant injury to the renal artery. This technique may potentially be used to treat various medical conditions, such as hypertension. The study was approved by the Institutional Animal Care and Use Committee. Ultrasound was applied to renal nerves of the swine model for histopathological evaluation. Therapeutic ultrasound energy was delivered circumferentially by an intravascular catheter maneuvered into the renal arteries. Fluoroscopic imaging was conducted pre-and post-ultrasound treatment. Animals were recovered and euthanized up to 30 hours post procedure, followed by necropsy and tissue sample collection. Histopathological examination showed evidence of extensive damage to renal nerves, characterized by nuclear pyknosis, hyalinization of stroma and multifocal hemorrhages, with little or no damage to renal arteries. This study demonstrates the feasibility of intravascular ultrasound as a minimally invasive renal denervation technique. Further studies are necessary to evaluate the long-term safety and efficacy of this technique and its related clinical significance.

  18. Vestibular implants studied in animal models: clinical and scientific implications.

    Science.gov (United States)

    Lewis, Richard F

    2016-12-01

    Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage. Copyright © 2016 the American Physiological Society.

  19. The application of animal models to study the biocompatibility of bicarbonate-buffered peritoneal dialysis solutions.

    Science.gov (United States)

    ter Wee, P M; Beelen, R H J; van den Born, J

    2003-12-01

    The application of animal models to study the biocompatibility of bicarbonate-buffered peritoneal dialysis solutions. Patients treated with peritoneal dialysis (PD) are at risk for development of ultrafiltration failure and peritonitis. These two significant complications can result in the termination of PD treatment. The relative unphysiologic composition of the currently used standard peritoneal dialysis fluids (PDF) is considered to be a major cause for the development of morphologic changes of the peritoneal membrane, ultimately resulting in ultrafiltration failure and probably contributing to changes in local defense mechanisms with the associated increased risk of peritonitis. In recent years, a major research focus has become the development of new and improved PD solutions. This has resulted in the development of an amino-acid-based PDF, a glucose polymer-based PDF, and several bicarbonate-buffered PDF. Typically, the first phase of biocompatibility testing of new PD solutions involves in vitro testing, employing isolated cells such as peritoneal macrophages or cell culture systems using human peritoneal mesothelial cells. The results of such evaluations are useful in providing insights into the biocompatibility performance of any given formulation, but suffer from several disadvantages, which can be better addressed using animal models. In vivo studies using animals permit the analysis of biocompatibility under conditions that allow for cell-to-cell interactions and dynamic changes in solution composition that more closely mimic the clinical situation. In this paper, we will review the use of animal models for the study of PDF biocompatibility and their application to the assessment of bicarbonate-buffered PDF.

  20. Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

    Science.gov (United States)

    Burns, Carol J.; McIntosh, Laura J.; Mink, Pamela J.; Jurek, Anne M.; Li, Abby A.

    2013-01-01

    Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective

  1. Pesticide exposure and neurodevelopmental outcomes: review of the epidemiologic and animal studies.

    Science.gov (United States)

    Burns, Carol J; McIntosh, Laura J; Mink, Pamela J; Jurek, Anne M; Li, Abby A

    2013-01-01

    Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective

  2. What do animals learn in artificial grammar studies?

    Science.gov (United States)

    Beckers, Gabriël J L; Berwick, Robert C; Okanoya, Kazuo; Bolhuis, Johan J

    2017-10-01

    Artificial grammar learning is a popular paradigm to study syntactic ability in nonhuman animals. Subjects are first trained to recognize strings of tokens that are sequenced according to grammatical rules. Next, to test if recognition depends on grammaticality, subjects are presented with grammar-consistent and grammar-violating test strings, which they should discriminate between. However, simpler cues may underlie discrimination if they are available. Here, we review stimulus design in a sample of studies that use particular sounds as tokens, and that claim or suggest their results demonstrate a form of sequence rule learning. To assess the extent of acoustic similarity between training and test strings, we use four simple measures corresponding to cues that are likely salient. All stimulus sets contain biases in similarity measures such that grammatical test stimuli resemble training stimuli acoustically more than do non-grammatical test stimuli. These biases may contribute to response behaviour, reducing the strength of grammatical explanations. We conclude that acoustic confounds are a blind spot in artificial grammar learning studies in nonhuman animals. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. Cereal grains for nutrition and health benefits: Overview of results from in vitro, animal and human studies in the HEALTHGRAIN project

    DEFF Research Database (Denmark)

    Björck, Inger; Östman, Elin; Kristensen, Mette

    2012-01-01

    Epidemiological studies have linked whole grain intake to the prevention of the metabolic syndrome, obesity and associated chronic diseases such as CVD and T2D. The Nutrition module within the HEALTHGRAIN project, included 10 partners and undertook in vitro, animal and human in vivo studies with ...

  4. Design for a high-resolution small-animal spect system usingpixellated Si(Li) detectors for in vivo Iodine-125 imaging

    Energy Technology Data Exchange (ETDEWEB)

    Choong, Woon-Seng; Moses, William W.; Tindall, Craig S.; Luke,Paul N.

    2004-08-01

    We propose a design for a high-resolution single-photon emission computed tomography (SPECT) system for in vivo {sup 125}I imaging in small animal using pixellated lithium-drifted silicon (Si(Li)) detectors. The proposed detectors are expected to have high interaction probability (>90%), good energy resolution (<15% FWHM), and good intrinsic spatial resolution ({approx}1 mm FWHM). The SPECT system will consist of a dual head detector geometry with the distance between the detectors ranging 30-50 mm to minimize the imaging distance between the mouse and the detectors. The detectors, each with an active area of 64 mm x 40 mm (64 x 40 array of 1 mm{sup 2} pixels and a 6 mm thick Si(Li) detector), will be mounted on a rotating gantry with an axial field-of-view of 64 mm. The detector signals will be read out by custom application-specific integrated circuits (ASICs). Using a high-resolution parallel-hole collimator, the expected spatial resolution is 1.6 mm FWHM at an imaging distance of 20 mm, and sensitivity is 6.7 cps/{micro}Ci. {sup 125}I is a readily available radioisotope with a long half-life of 59.4 days and it is commonly used to label biological compounds in molecular biology. Conventional gamma cameras are not optimized to detect the low emission energies (27 to 35 keV) of {sup 125}I. However, Si(Li) detector provides an ideal solution for detecting the low-energy emissions of {sup 125}I. In addition to presenting the design of the system, this paper presents a feasibility study of using Si(Li) detectors to detect the emissions of {sup 125}I.

  5. Effect of in vivo ozone exposure to Dorset sheep, an animal model with low levels of erythrocyte glucose-6-phosphate dehydrogenase activity

    Energy Technology Data Exchange (ETDEWEB)

    Moore, G.S.; Calabrese, E.J.; Schulz, E.

    1981-02-01

    Considerable interest has recently been directed to the possible extrapulmonary effects caused by exposure to ambient ozone. As a result of ozone induced in vivo alteration of red cell function within human subjects, it has been hypothesized that individuals with an erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency would be at increased hemolytic risk to elevated ambient ozone exposure. In order to evaluate such an hypothesis in an experimental setting it would be of great value to have an appropriate animal model with erythrocyte G-6-PD activity similar to the absolute activity range found in the human population. While no such unique animal model is presently known, the literature has revealed that Dorset sheep have an erythrocyte G-6-PD activity comparable in absolute units to a human G-6-PD deficient. Based on this information, we evaluated the mechanisms by which sheep and human G-6-PD deficient red cells handle oxidant stress. We evaluated the effects of in vivo ozone exposure in Dorset sheep over a broad range of concentrations.

  6. Antinociceptive properties of shikonin: in vitro and in vivo studies.

    Science.gov (United States)

    Gupta, Bhawana; Chakraborty, Sabyasachi; Saha, Soumya; Chandel, Sunita Gulabsingh; Baranwal, Atul Kumar; Banerjee, Manish; Chatterjee, Mousumi; Chaudhury, Ashok

    2016-07-01

    Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 μmol/L and 6.4 μmol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ∼71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker.

  7. Animal studies with the Carmat bioprosthetic total artificial heart.

    Science.gov (United States)

    Latrémouille, Christian; Duveau, Daniel; Cholley, Bernard; Zilberstein, Luca; Belbis, Guillaume; Boughenou, Marie-Fazia; Meleard, Denis; Bruneval, Patrick; Adam, Clovis; Neuschwander, Arthur; Perles, Jean-Christophe; Jansen, Piet; Carpentier, Alain

    2015-05-01

    The Carmat bioprosthetic total artificial heart (TAH) contains bioprosthetic blood-contacting surfaces, and is designed for orthotopic cardiac replacement. In preparation for clinical studies, we evaluated the TAH performance and its effects on end-organ function in an animal model. Twelve female Charolais calves, 2-3 months of age and weighing 102-122 kg, were implanted with the TAH through a mid-sternotomy to ensure an adequate anatomic fit. The intended support duration was 4-10 days. Haematological values, creatinine, bilirubin and lactate levels were measured and mean arterial and central venous pressure, central venous oxygen saturation and TAH parameters were monitored. The calves were placed in a cage immediately postoperatively, and extubated on postoperative day 1 in most cases. Average support duration was 3 days, with 4 of 12 calves supported for 4, 4, 8 and 10 days. The initial procedures were used to refine surgical techniques and postoperative care. Pump output ranged from 7.3 to 10 l/min. Haemodynamic parameters and blood analysis were within acceptable ranges. No device failures occurred. No anticoagulation was used in the postoperative phase. The calves were euthanized in case of discomfort compromising the animal well-being, such as respiratory dysfunction, severe blood loss and cerebral dysfunction. Device explant analysis showed no thrombus formation inside the blood cavities. Histological examination of kidneys showed isolated micro-infarction in 2/12 animals; brain histology revealed no thromboembolic depositions. The Carmat bioprosthetic TAH implanted in calves up to 10 days provided adequate blood flow to organs and tissues. Low levels of haemolysis and no visible evidence of thromboembolic depositions in major organs and device cavities, without the use of anticoagulation, may indicate early-phase haemocompatibility of the TAH. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio

  8. Potential for clonal animals in longevity and ageing studies.

    Science.gov (United States)

    Nilsson Sköld, Helen; Obst, Matthias

    2011-10-01

    Ageing is defined as a decline in reproductive and/or somatic performance over time, and as such is experienced by most organisms. Evolutionary theories explain ageing as a consequence of reduced selection pressure against mutations and reduced allocation to somatic maintenance in post-reproductive individuals. In addition, the fecundity of younger age-groups makes a more significant contribution than infinite maintenance of the parental body to the production of subsequent generations. However, in clonal animals, as well as in plants that reproduce by agametic cloning, the adult body is itself a reproductive unit that increases its fitness as a function of genet size. Given the apparent longevity of many such clonal organisms, species undergoing agametic cloning are often assumed to be non-ageing and even potentially immortal. Here, we present a brief overview of ageing in organisms undergoing agametic cloning, focusing on animals and molecular investigation. We discuss molecular and evolutionary aspects of ageing or non-ageing with respect to selection in clonal species. Of particular relevance to the search for potential mechanistic processes behind longevity is the notion that clonal organisms are frequently smaller than their obligate sexual counterparts. In conclusion, we find that while clonal animals also commonly age, evolutionary arguments together with empirical evidence suggest that they are likely to be long-lived and stress resistant at the genet level. However, theoretical modeling continues to predict the possibility of immortality, if the contribution from sexual reproduction is low. Future in-depth study of long-lived clones should present an excellent opportunity to discover novel mechanisms for renewal and long-term somatic maintenance and health.

  9. Acupuncture points for treating Parkinson's disease based on animal studies.

    Science.gov (United States)

    Kwon, Sunoh; Seo, Byung-Kwan; Kim, Seungtae

    2016-10-01

    Parkinson's disease (PD) is a well-known neurodegenerative disease caused by dopaminergic cell death in the nigrostriatal pathway. Recent studies have shown that acupuncture can be a potential therapy for the treatment of PD, but it is not clear which acupuncture points (acupoints) play major roles in reliving symptoms of PD. Yanglingquan (GB 34), Zusanli (ST 36), Fengfu (GV 16), Taichong (LR 3), Baihui (GV 20) and Dazhui (GV 14) acupoints have frequently been to investigate the effectiveness and action mechanism of acupuncture for treating PD, but it is not clear why they were selected. This review summarizes the current understanding of the acupoints for PD treatment based on Oriental medicine theories and on the accumulated findings from previous animal studies. The results of this study will be useful to development of a strategy for future research in this field.

  10. Redox regulation of ischemic limb neovascularization – What we have learned from animal studies

    Directory of Open Access Journals (Sweden)

    Reiko Matsui

    2017-08-01

    Full Text Available Mouse hindlimb ischemia has been widely used as a model to study peripheral artery disease. Genetic modulation of the enzymatic source of oxidants or components of the antioxidant system reveal that physiological levels of oxidants are essential to promote the process of arteriogenesis and angiogenesis after femoral artery occlusion, although mice with diabetes or atherosclerosis may have higher deleterious levels of oxidants. Therefore, fine control of oxidants is required to stimulate vascularization in the limb muscle. Oxidants transduce cellular signaling through oxidative modifications of redox sensitive cysteine thiols. Of particular importance, the reversible modification with abundant glutathione, called S-glutathionylation (or GSH adducts, is relatively stable and alters protein function including signaling, transcription, and cytoskeletal arrangement. Glutaredoxin-1 (Glrx is an enzyme which catalyzes reversal of GSH adducts, and does not scavenge oxidants itself. Glrx may control redox signaling under fluctuation of oxidants levels. In ischemic muscle increased GSH adducts through Glrx deletion improves in vivo limb revascularization, indicating endogenous Glrx has anti-angiogenic roles. In accordance, Glrx overexpression attenuates VEGF signaling in vitro and ischemic vascularization in vivo. There are several Glrx targets including HIF-1α which may contribute to inhibition of vascularization by reducing GSH adducts. These animal studies provide a caution that excess antioxidants may be counter-productive for treatment of ischemic limbs, and highlights Glrx as a potential therapeutic target to improve ischemic limb vascularization.

  11. Electron microscopy methods for studying in vivo DNA replication intermediates.

    Science.gov (United States)

    Lopes, Massimo

    2009-01-01

    The detailed understanding of the DNA replication process requires structural insight. The combination of psoralen crosslinking and electron microscopy has been extensively exploited to reveal the fine architecture of in vivo DNA replication intermediates. This approach proved instrumental to uncover the basic mechanisms of DNA duplication, as well as the perturbation of this process by genotoxic treatments. The replication structures need to the stabilized in vivo (by psoralen crosslinking) prior to extraction and enrichment procedures, finally leading to the visualization at the transmission electron microscope. This chapter outlines the procedures required to visualize in vivo replication intermediates of genomic DNA, extracted from budding yeast or cultured mammalian cells.

  12. Effect of chronic treatment with Rosiglitazone on Leydig cell steroidogenesis in rats: In vivo and ex vivo studies

    Directory of Open Access Journals (Sweden)

    Lima Maria C

    2010-02-01

    Full Text Available Abstract Background The present study was designed to examine the effect of chronic treatment with rosiglitazone - thiazolidinedione used in the treatment of type 2 diabetes mellitus for its insulin sensitizing effects - on the Leydig cell steroidogenic capacity and expression of the steroidogenic acute regulatory protein (StAR and cholesterol side-chain cleavage enzyme (P450scc in normal adult rats. Methods Twelve adult male Wistar rats were treated with rosiglitazone (5 mg/kg administered by gavage for 15 days. Twelve control animals were treated with the vehicle. The ability of rosiglitazone to directly affect the production of testosterone by Leydig cells ex vivo was evaluated using isolated Leydig cells from rosiglitazone-treated rats. Testosterone production was induced either by activators of the cAMP/PKA pathway (hCG and dbcAMP or substrates of steroidogenesis [22(R-hydroxy-cholesterol (22(R-OH-C, which is a substrate for the P450scc enzyme, and pregnenolone, which is the product of the P450scc-catalyzed step]. Testosterone in plasma and in incubation medium was measured by radioimmunoassay. The StAR and P450scc expression was detected by immunocytochemistry. Results The levels of total circulating testosterone were not altered by rosiglitazone treatment. A decrease in basal or induced testosterone production occurred in the Leydig cells of rosiglitazone-treated rats. The ultrastructural and immunocytochemical analysis of Leydig cells from rosiglitazone-treated rats revealed cells with characteristics of increased activity as well as increased StAR and P450scc expression, which are key proteins in androgen biosynthesis. However, a number of rosiglitazone-treated cells exhibited significant mitochondrial damage. Conclusion The results revealed that the Leydig cells from rosiglitazone-treated rats showed significant reduction in testosterone production under basal, hCG/dbcAMP- or 22 (R-OH-C/pregnenolone-induced conditions, although

  13. Mood Disorders Are Glial Disorders: Evidence from In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Matthias L. Schroeter

    2010-01-01

    Full Text Available It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Successful antidepressive treatment reduces S100B in major depression whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered. By indicating glial alterations without neuronal changes, serum S100B studies confirm specific glial pathology in mood disorders in vivo. S100B can be regarded as a potential diagnostic biomarker for mood disorders and as a biomarker for successful antidepressive treatment.

  14. Formulation Study of Topically Applied Lotion: In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Syed Nisar Hussain Shah

    2013-01-01

    Full Text Available ntroduction: This article presents the development and evaluation of a new topical formulation of diclofenac diethylamine (DDA as a locally applied analgesic lotion. Methods: To this end, the lotion formulations were formulated with equal volume of varying concentrations (1%, 2%, 3%, 4%; v/v of permeation enhancers, namely propylene glycol (PG and turpentine oil (TO. These lotions were subjected to physical studies (pH, viscosity, spreadability, homogeneity, and accelerated stability, in vitro permeation, in vivo animal studies and sensatory perception testing. In vitro permeation of DDA from lotion formulations was evaluated across polydimethylsiloxane membrane and rabbit skin using Franz cells. Results: It was found that PG and TO content influenced the permeation of DDA across model membranes with the lotion containing 4% v/v PG and TO content showed maximum permeation enhancement of DDA. The flux values for L4 were 1.20±0.02 μg.cm-2.min-1 and 0.67 ± 0.02 μg.cm-2.min-1 for polydimethylsiloxane and rabbit skin, respectively. Flux values were significantly different (p < 0.05 from that of the control. The flux enhancement ratio of DDA from L4 was 31.6-fold and 4.8-fold for polydimethylsiloxane and rabbit skin, respectively. In the in vivo animal testing, lotion with 4% v/v enhancer content showed maximum anti-inflammatory and analgesic effect without inducing any irritation. Sensatory perception tests involving healthy volunteers rated the formulations between 3 and 4 (values ranging between -4 to +4, indicating a range of very bad to excellent, respectively. Conclusion: It was concluded that the DDA lotion containing 4% v/v PG and TO exhibit the best performance overall and that this specific formulation should be the basis for further clinical investigations.

  15. Placental glucose transfer: a human in vivo study.

    Directory of Open Access Journals (Sweden)

    Ane M Holme

    Full Text Available The placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply determines the fetal venous-arterial glucose difference (reflecting fetal consumption.Cross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein and outgoing vessels (uterine vein and umbilical artery.There were significant mean (SD uteroplacental arterio-venous 0.29 (0.23 mmol/L and fetal venous-arterial 0.38 (0.31 mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42 mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001, but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001 and the glucose concentration in the umbilical artery (r = -0.45, p = 0.004. Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001, but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values.We did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly

  16. Animal models for studying respiratory syncytial virus infection and its long term effects on lung function.

    Science.gov (United States)

    Domachowske, Joseph B; Bonville, Cynthia A; Rosenberg, Helene F

    2004-11-01

    Human respiratory syncytial virus (hRSV) infection causes a spectrum of illnesses ranging from mild infection to life-threatening bronchiolitis and respiratory failure. Human studies on the pathogenesis of RSV infection are invaluable, but animal models permit advances with the use of experimental strategies that would be inappropriate in human studies. We review the advantages and disadvantages of various animal models for the study of hRSV infection. No animal model of hRSV infection replicates the complete spectrum of disease severity seen in humans. Available models differ in their ability to incorporate genetic technology and to allow the study of immunity, vaccine efficacy and treatment interventions. Although hRSV establishes disease in primates, this advantage is outweighed by the impracticalities and cost of using such models. The study of bovine RSV infection in calves is appealing because of parallels with human disease. Among rodent models, BALB/c mice have helped delineate the mechanisms underlying vaccine-enhanced RSV disease, and cotton rats have been used for preclinical testing. The single major disadvantage of studying hRSV in rodent models is the limited extent to which this host-restricted human pneumovirus replicates in mouse lung tissue. The rodent-specific Pneumovirus pathogen, pneumonia virus of mice, causes an infection that mirrors severe bronchiolitis and pneumonia in infants infected with RSV, including robust virus replication with profound inflammation. The recent development of the pneumonia virus of mice model has permitted exploration of the mechanisms of severe Pneumovirus disease in vivo with the use of sophisticated genetic tools and genetically manipulated mouse strains.

  17. Epidemiological Study of Animal Leptospirosis in New Caledonia

    Directory of Open Access Journals (Sweden)

    Cédric Roqueplo

    2013-01-01

    Full Text Available Leptospirosis is an important zoonotic disease in the world and a real public health concern for many years in New Caledonia. A cross-sectional survey was carried out on domestic and wild animals from New Caledonia in April 2009. Blood samples were collected from 30 cattle, 29 deers, (Cervus timorensis russa, 25 horses, 51 dogs, and 8 cats and were tested for 23 serovars of pathogenic Leptospira species by the microscopic agglutination test. From the total number of 143 samples, 84 (58.7% were found to be positive towards one or several serovars of pathogenic leptospires. According to the species, the positive sera were obtained from 43% of 30 cattle, 72% of 29 Rusa deer, 80% of 25 horses, and 43% of 51 dogs, and fromall of the 8 cats tested. This study shows the broad dispersion and the high prevalence of the different serogroups of pathogenic Leptospira species tested, particularly among deer and horses. The disease is endemic in domestic animals and concerns all the species.

  18. Animal models as tools to study the pathophysiology of depression

    Directory of Open Access Journals (Sweden)

    Helena M. Abelaira

    2013-01-01

    Full Text Available The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response.

  19. Large scale in vivo recordings to study neuronal biophysics.

    Science.gov (United States)

    Giocomo, Lisa M

    2015-06-01

    Over the last several years, technological advances have enabled researchers to more readily observe single-cell membrane biophysics in awake, behaving animals. Studies utilizing these technologies have provided important insights into the mechanisms generating functional neural codes in both sensory and non-sensory cortical circuits. Crucial for a deeper understanding of how membrane biophysics control circuit dynamics however, is a continued effort to move toward large scale studies of membrane biophysics, in terms of the numbers of neurons and ion channels examined. Future work faces a number of theoretical and technical challenges on this front but recent technological developments hold great promise for a larger scale understanding of how membrane biophysics contribute to circuit coding and computation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Nicotine addiction: studies about vulnerability, epigenesis and animal models

    Directory of Open Access Journals (Sweden)

    Bernabeu, Ramon

    2013-07-01

    Full Text Available This article is a summary about the current research of nicotine effects on the nervous system and its relationship to the generation of an addictive behavior. Like other drugs of abuse, nicotine activates the reward pathway, which in turn is involved in certain psychiatric diseases. There are individuals who have a high vulnerability to nicotine addiction. This may be due to genetic and epigenetic factors and/or the environment. In this review, we described some epigenetic factors that may be involved in those phenomena. The two animal models most widely used for studying the reinforcing effects of nicotine are: self-administration and conditioning place preference (CPP. Here, we emphasized the CPP, due to its potential application in humans. In addition, we described the locomotor activity model (as a measure of psychostimulant effects to study vulnerability to drugs of abuse

  1. Towards ethically improved animal experimentation in the study of animal reproduction.

    Science.gov (United States)

    Blache, D; Martin, G B; Maloney, S K

    2008-07-01

    The ethics of animal-based research is a continuing area of debate, but ethical research protocols do not prevent scientific progress. In this paper, we argue that our current knowledge of the factors that affect reproductive processes provides researchers with a solid foundation upon which they can conduct more ethical research and simultaneously produce data of higher quality. We support this argument by showing how a deep understanding of the genetics, nutrition and temperament of our experimental animals can improve compliance with two of the '3 Rs', reduction and refinement, simply by offering better control over the variance in our experimental model. The outcome is a better experimental design, on both ethical and scientific grounds.

  2. Microbicide safety/efficacy studies in animals: macaques and small animal models.

    Science.gov (United States)

    Veazey, Ronald S

    2008-09-01

    A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. The unique host and cell specificity of HIV, however, provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a prerequisite for advancing additional microbicide candidates to human clinical trials.

  3. In vivo localization studies in the stramenopile alga Nannochloropsis oceanica.

    Science.gov (United States)

    Moog, Daniel; Stork, Simone; Reislöhner, Sven; Grosche, Christopher; Maier, Uwe-G

    2015-02-01

    The tiny eustigmatophyte Nannochloropsis sp. recently emerged as a promising model organism for biotechnology as it possesses a considerably high cellular oil content interesting for biodiesel production. Furthermore, the alga was shown to be genetically well accessible providing powerful tools for biotechnological engineering as well as basic research. Nannochloropsis sp. can be transformed very efficiently taking advantage of homologous recombination, however, so far it remained unclear whether these organisms are also suitable model systems for in vivo protein localization studies due to their small cell size. Here we present, to our knowledge, the first protein localization studies based on the expression of chimeric fluorescent fusion proteins in the genus Nannochloropsis using N. oceanica CCMP1779 as a model organism. Besides expressing a cytosolic green fluorescent protein (GFP), the reporter could be directed into subcellular structures such as the mitochondria, the endoplasmic reticulum and secretory pathway as well as the complex plastid including the periplastidal compartment and the stroma via fusion of specific N-terminal targeting sequences. These results expand the potential of N. oceanica as a model system in biotechnology as well as cellular biology for which now an almost complete molecular tool set exists. Copyright © 2015 Elsevier GmbH. All rights reserved.

  4. An ex vivo spinal cord injury model to study ependymal cells in adult mouse tissue.

    Science.gov (United States)

    Fernandez-Zafra, Teresa; Codeluppi, Simone; Uhlén, Per

    2017-08-15

    Traumatic spinal cord injury is characterized by an initial cell loss that is followed by a concerted cellular response in an attempt to restore the damaged tissue. Nevertheless, little is known about the signaling mechanisms governing the cellular response to injury. Here, we have established an adult ex vivo system that exhibits multiple hallmarks of spinal cord injury and allows the study of complex processes that are difficult to address using animal models. We have characterized the ependymal cell response to injury in this model system and found that ependymal cells can become activated, proliferate, migrate out of the central canal lining and differentiate in a manner resembling the in vivo situation. Moreover, we show that these cells respond to external adenosine triphosphate and exhibit spontaneous Ca(2+) activity, processes that may play a significant role in the regulation of their response to spinal cord injury. This model provides an attractive tool to deepen our understanding of the ependymal cell response after spinal cord injury, which may contribute to the development of new treatment options for spinal cord injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Epidemiological studies on animal and human trichinellosis in Estonia

    Directory of Open Access Journals (Sweden)

    Järvis T.

    2001-06-01

    Full Text Available From 1992 to 1999, muscle samples from 814 sylvatic animals and 1,173 domestic and synanthropic animals were collected in 15 districts of Estonia ; the prevalence of trichinellosis ranged from 1.0 % to 79.4 % for sylvatic animals and from 0.6 % to 24.5 % for domestic or synanthropic animals and for animals from fur-bearing farms. The most important reservoirs of Trichinella in nature were the raccoon dog, the red fox, the lynx and the wolf. Three species of Trichinella (T. spiralis, T. nativa, and T. britovi were identified by several types of PCR-based analyses. Meat from sylvatic animals was the main source of Trichinella infection for humans.

  6. Non-invasive, Contrast-enhanced Spectral Imaging of Breast Cancer Signatures in Preclinical Animal Models In vivo.

    Science.gov (United States)

    Ramanujan, V Krishnan; Ren, Songyang; Park, Sangyong; Farkas, Daniel L

    2010-10-02

    We report here a non-invasive multispectral imaging platform for monitoring spectral reflectance and fluorescence images from primary breast carcinoma and metastatic lymph nodes in preclinical rat model in vivo. The system is built around a monochromator light source and an acousto-optic tunable filter (AOTF) for spectral selection. Quantitative analysis of the measured reflectance profiles in the presence of a widely-used lymphazurin dye clearly demonstrates the capability of the proposed imaging platform to detect tumor-associated spectral signatures in the primary tumors as well as metastatic lymphatics. Tumor-associated changes in vascular oxygenation and interstitial fluid pressure are reasoned to be the physiological sources of the measured reflectance profiles. We also discuss the translational potential of our imaging platform in intra-operative clinical setting.

  7. Learning Curve in a Western Training Center of the Circumferential En Bloc Esophageal Endoscopic Submucosal Dissection in an In Vivo Animal Model

    Directory of Open Access Journals (Sweden)

    Miguel A. Tanimoto

    2011-01-01

    Full Text Available Aim. Evaluate the feasibility to overcome the learning curve in a western training center of the en bloc circumferential esophageal (ECE- ESD in an in vivo animal model. Methods. ECE-ESD was performed on ten canine models under general anesthesia on artificial lesions at the esophagus marked with coagulation points. After the ESD each canine model was euthanized and surgical resection of the esophagus and stomach was carried out according to “the Principles of Humane Experimental Technique, Russel and Burch.” The specimen was fixed with needles on cork submerged in formalin with the esophagus and stomach then delivered to the pathology department to be analyzed. Results. ECE-ESD was completed without complications in the last 3/10 animal models. Mean duration for the procedures was 192±35 minutes (range 140–235 minutes. All the procedures were done at the animal lab surgery room with cardio pulmonary monitoring and artificial ventilation by staff surgery members and a staff member of the Gastroenterology department trained during 1999–2001 at the Fujigaoka hospital of the Showa U. in Yokohama, Japan, length (range 15–18 mm and 51±6.99 width (range 40–60 mm. Conclusion. ECE-ESD training is feasible in canine models for postgraduate endoscopy fellows.

  8. Laser welding and syncristallization techniques comparison: "Ex vivo" study.

    Science.gov (United States)

    Fornaini, Carlo; Meleti, Marco; Vescovi, Paolo; Merigo, Elisabetta; Rocca, Jean-Paul

    2013-12-30

    Stabilization of implant abutments through electric impulses at high voltage for a very short time (electrowelding) was developed in the Eighties. In 2009, the same procedure was performed through the use of laser (laser welding) The aim of this study is to compare electrowelding and laser welding for intra-oral implant abutments stabilization on "ex vivo models" (pig jaws). Six bars were welded with two different devices (Nd:YAG laser and Electrowelder) to eighteen titanium implant abutment inserted in three pig jaws. During the welding process, thermal increase was recorded, through the use of k-thermocouples, in the bone close to the implants. The strength of the welded joints was evaluated by a traction test after the removal of the implants. For temperature measurements a descriptive analysis and for traction test "values unpaired t test with Welch's correction" were performed: the significance level was set at Pwelding gives a lower thermal increase than Electrowelding at the bone close to implants (Mean: 1.97 and 5.27); the strength of laser welded joints was higher than that of Electrowelding even if nor statistically significant. (Mean: 184.75 and 168.29) CONCLUSION: Electrowelding seems to have no advantages, in term of thermal elevation and strength, while laser welding may be employed to connect titanium implants for immediate load without risks of thermal damage at surrounding tissues.

  9. In vivo studies of biotin absorption in distal rat intestine

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, B.B.; Rosenberg, I.H.

    1986-03-01

    The authors have extended their previous studies of biotin absorption in rat proximal jejunum (PJ) to examine biotin absorptive capacity of rat ileum (I) and proximal colon (PC) using in vivo intestinal loop technique. Intestinal loops (2.5 cm) were filled with 0.3 ml of solution containing (/sup 3/H)-biotin and (/sup 14/C)-inulin in phosphate buffer, pH 6.5. Biotin absorption was determined on the basis of luminal biotin disappearance after correction for inulin recovery and averaged (pmol/loop-10 min; X +/- SEM). In related experiments, 5-cm loops of PJ, distal I (DI), or PC were filled with 0.5 ml of solution of similar composition (1.0 ..mu..M biotin). The abdominal cavity was closed and the rats were allowed to recover from anesthesia, then sacrificed 3 hr after injection. Biotin absorption averaged 96.2% (PJ), 93.2% (DI), and 25.8% (PC) of the dose administered. These differences were reflected in the radioactive biotin content of plasma and intestinal loop, kidney, and liver. These data demonstrate significant biotin absorption in rat DI and PC, as required if the intestinal microflora are to be considered as a source of biotin for the host.

  10. In Vivo Toxicity Studies of Europium Hydroxide Nanorods in Mice

    Science.gov (United States)

    Patra, Chitta Ranjan; Abdel Moneim, Soha S.; Wang, Enfeng; Dutta, Shamit; Patra, Sujata; Eshed, Michal; Mukherjee, Priyabrata; Gedanken, Aharon; Shah, Vijay H; Mukhopadhyay, Debabrata

    2009-01-01

    Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence properties and pro-angiogenic to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [EuIII(OH)3] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mgKg−1day−1) and time dependent manner (8–60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice sacrificed on day 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods. PMID:19616569

  11. Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies

    Science.gov (United States)

    Cogoli, A.

    1996-01-01

    The study of the function of immune cells in microgravity has been studied for more than 20 years in several laboratories. It is clear today that the immune system is depressed in more than 50% of the astronauts during and after space flight and that the activation of T lymphocytes by mitogens in vitro changes dramatically. This article gives an overview of the gravitational studies conducted by our laboratory in Spacelab, in MIR station, in sounding rockets and on the ground in the clinostat and the centrifuge. Three experimental approaches are followed in our work: (i) Ex vivo studies are performed with blood samples drawn from astronauts; (ii) in vivo studies are based on the application of seven antigens to the skin of the astronauts; (iii) in vitro studies are carried out with immune cells purified from the blood of healthy donors (not astronauts). The data from our in vivo and ex vivo studies are in agreement with those of other laboratories and show that the immunological function is depressed in the majority of astronauts as a consequence of the stress of space flight rather than by a direct influence of gravity on the cell. Immune depression may become a critical hazard on long duration flights on space stations or to other planets. In vitro experiments show that cultures of free-floating lymphocytes and monocytes undergo a dramatic depression of activation by the mitogen concanavalin A, while activation is more than doubled when the cells are attached to microcarrier beads. Such effects may be attributed to both direct and indirect effects of gravitational unloading on basic biological mechanisms of the cell. While the in vitro data are very important to clarify certain aspects of the biological mechanism of T cells activation, they are not descriptive of the changes of the immunological function of the astronauts.

  12. A retrospective study on incidence of lameness in domestic animals

    Directory of Open Access Journals (Sweden)

    A. Mohsina

    2014-08-01

    Full Text Available Aim: To study the incidence of lameness among different species of animals presented to the Veterinary Polyclinic, Indian Veterinary Research Institute, Izatnagar. Materials and Methods: Outpatient department (OPD records for the period from January 2006 to December 2010 were referred and information was collected regarding number of lameness in different species, breeds, type of injury, limb affected, gender, age at onset, treatment offered, outcome and any reoccurrence. In this study, fractured cases were not included. Results: The incidence of lameness among different species were recorded: canine (56%, equine (21%, caprine (7%, feline (3%, cattle (7%, buffalo (5.47%, sheep (0.6%, monkey (0.39% and swine (0.19%. In dog, the different conditions were reported with hind quarter weakness recording 55% of lameness followed by right hind limb lameness (14.7%, left hind limb lameness (12.6%, left forelimb lameness (12%, hip dislocation (6.3% and hip dysplasia (4.2%. In caprines, important causes of lameness were right forelimb lameness (23%, right hind limb lameness (12%, left forelimb lameness (12%, posterior paresis (9%, left shoulder dislocation (14% and right shoulder dislocation (6%. In cattle, 34.28% of cases with right hind limb lameness, 28.5% cases were due to HQW, 14.28% had hip dysplasia, 8.57% suffered left hind limb lameness, 6% cases were recorded with obturator nerve paralysis and 8.57% cases suffered contracted tendon in calves. In buffaloes, cases reported were right carpal arthritis, foot rot and left hind limb lameness (14.28% each, due to bilateral upward luxation of patella and due bilateral purulent wound in stifle (18% each and hip dislocation (21.4%. In equines, lameness were reported with right hind limb affection (13%, left forelimb affection (11%, right forelimb affection (17%, 4% each due to disease of right shoulder, HQW and both forelimb affection, lateral dislocation of patella (3%, affection of both hind limbs (9%, 5

  13. In vivo evaluation of different alterations of redox status by studying pharmacokinetics of nitroxides using magnetic resonance techniques

    Directory of Open Access Journals (Sweden)

    Goran Bačić

    2016-08-01

    Full Text Available Free radicals, particularly reactive oxygen species (ROS, are involved in various pathologies, injuries related to radiation, ischemia-reperfusion or ageing. Unfortunately, it is virtually impossible to directly detect free radicals in vivo, but the redox status of the whole organism or particular organ can be studied in vivo by using magnetic resonance techniques (EPR and MRI and paramagnetic stable free radicals – nitroxides. Here we review results obtained in vivo following the pharmacokinetics of nitroxides on experimental animals (and a few in humans under various conditions. The focus was on conditions where the redox status has been altered by induced diseases or harmful agents, clearly demonstrating that various EPR/MRI/nitroxide combinations can reliably detect metabolically induced changes in the redox status of organs. These findings can improve our understanding of oxidative stress and provide a basis for studying the effectiveness of interventions aimed to modulate oxidative stress. Also, we anticipate that the in vivo EPR/MRI approach in studying the redox status can play a vital role in the clinical management of various pathologies in the years to come providing the development of adequate equipment and probes.

  14. Animal Rights: Selected Resources and Suggestions for Further Study.

    Science.gov (United States)

    Davidoff, Donald J.

    1989-01-01

    Presents an annotated list of selected resources intended to serve as a guide to the growing amount of material on animal rights. Suggestions to aid in additional research include subject headings used to find books, indexes used to locate periodical articles, sources for locating organizations, and a selected list of animal rights organizations.…

  15. Studies to distinguish between human and animal faecal pollution ...

    African Journals Online (AJOL)

    Human enteric viral infections are considered to be predominantly associated with human wastes, as opposed to animal wastes, and a distinction between these has benefits for water quality control and risk assessment. A variety of techniques have been described to distinguish between human and animal faecal pollution ...

  16. Small Animal [{sup 18}F]FDG PET Imaging for Tumor Model Study

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sang Keun; Kim, Kyeong Min; Cheon, Gi Jeong [Radiological and Medical Sciences Research Institute, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-02-15

    PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [{sup 18}F]FDG has been successfully applied to investigation of metabolism, receptor, ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [{sup 18}F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [{sup 18}F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model.

  17. Impact of Environmental Enrichment Devices on NTP In Vivo Studies.

    Science.gov (United States)

    Churchill, Sheba R; Morgan, Daniel L; Kissling, Grace E; Travlos, Gregory S; King-Herbert, Angela P

    2016-02-01

    The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices. © The Author(s) 2016.

  18. Ex vivo and in vivo topographic studies of bladder by optical coherence tomography (Invited Paper)

    Science.gov (United States)

    Daniltchenko, Dmitri; Sachs, Markus D.; Lankenau, Eva; Koenig, Frank; Burkhardt, Mick; Huettmann, Gereon; Kristiansen, Glen; Schnorr, Dietmar; Al-Shukri, Salman; Loening, Stefan A.

    2005-06-01

    Conventional imaging modalities like CT or ultrasonography have a spatial resolution of 70-1000 rim. OCT is a new method by which light of a certain wavelength is introduced into a fiberglass optic to measure tissue structures of up to 2.5 mm depth with a spatial resolution of up to 10-15 μm. We utilized the Tomograph Sirius 713, developed at the Medical Laser Centre in cooperation with 4-Optics AG, Lubeck, Germany. This apparatus uses a special Super- Luminescence-Diode (SLD) that produces light within the near infrared wavelength, with a central wavelength of 1300 nm. The coherence length is reduced to 15 μm. The light is introduced into a fiberglass optic which is several meters long and is easy to handle. To measure the depth of invasion and position of urothelial bladder tumors, the fiberglass optic is attached to a regular endoscope (Wolf, Knittlingen, Germany) via an OCT adapter. That way, in parallel to the regular endoscopic view of the bladder mucosa with or without pathologic findings, an OCT picture of the superficial as well as the deeper muscle layers is visible online. OCT was used to obtain 945 images from the bladder in vivo und ex vivo of 65 patients. OCT of normal bladder mucosa allows to image a cross section of up to 2.5 mm. It is possible to distinguish transitional epithelium, lamina propria, smooth muscles and capillaries. In cystitis, the thickness of the mucosa is constant, but the distinction between the different layers is blurred. In squamous metaplasia there is thickening of the epithelial layer, with preservation of lamination of the lower layers. In transitional cell carcinoma there is a complete loss of the regular layered structure. It is easily possible to distinguish the border between tumour and normal bladder tissue. OCT is a new high-resolution imaging procedure. It has the potential to improve the diagnostics of the urothelium and its lesions. In conjunction with a highly sensitive orientating procedure like fluorescence

  19. In and ex vivo breast disease study by Raman spectroscopy

    DEFF Research Database (Denmark)

    Raniero, L.; Canevari, R. A.; Ramalho, L. N. Z.

    2011-01-01

    In this work, Raman spectra in the 900-1,800 cm(-1) wavenumber region of in vivo and ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured. In the case of the in vivo tissues, the Raman spectra were collected for both transcutaneous...... (with skin) and skin-removed tissues. To identify the spectral differences between normal and cancer breast tissue, the paired t-test was carried out for each wavenumber using the whole spectral range from both groups. Quadratic discriminate analysis based on principal component analysis (PCA) was also...... used to determine and evaluate differences in the Raman spectra for the various samples as a basis for diagnostic purposes. The differences in the Raman spectra of the samples were due to biochemical changes at the molecular, cellular and tissue levels. The sensitivity and specificity...

  20. A novel approach to teaching surgical skills to medical students using an ex vivo animal training model.

    Science.gov (United States)

    Bauer, Florian; Rommel, Niklas; Kreutzer, Kilian; Weitz, Jochen; Wagenpfeil, Stefan; Gulati, Aakshay; Wolff, Klaus-Dietrich; Kesting, Marco R

    2014-01-01

    Traditional surgical teaching is influenced by restrictive factors, such as financial pressures and ethical constraints. The teaching of surgical skills during a medical school education seems not to be robust enough at present, possibly resulting in stressful circumstance for surgical novices. However, the authors are convinced that practical training is fundamental for preparing medical students optimally for challenges in the operating theater and have, therefore, examined a novel method of teaching basic surgical skills to medical students. A total of 20 medical students received surgical skill training, which included theoretical lessons, working with ex vivo pig training models, and active participation in the operating theater. All the trainees took written tests and were rated in an Objective Structured Clinical Examination. Before and after training, the students completed a self-assessment form involving the choice of the correct surgical indication and the performance of surgical procedures. The students' performance in the written examination and in the Objective Structured Clinical Examination increased significantly after training (p ≤ 0.001). Furthermore, the evaluation of the self-assessment form revealed significant improvements in all categories (p ≤ 0.001). Our surgical training method appears to improve the surgical abilities of medical students and to increase their self-confidence with respect to surgical procedures. Therefore, the authors recommend the integration of this method into the medical school curriculum to prepare medical students well for surgical challenges. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  1. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

    Science.gov (United States)

    Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

    2014-11-01

    To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

  2. Heat Shock Protein 72 Expressing Stress in Sepsis: Unbridgeable Gap between Animal and Human Studies—A Hypothetical “Comparative” Study

    Directory of Open Access Journals (Sweden)

    George Briassoulis

    2014-01-01

    Full Text Available Heat shock protein 72 (Hsp72 exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical “comparative study” model. Forty-one in vivo (56.1%, in vitro (17.1%, or combined (26.8% animal and 14 in vivo (2 or in vitro (12 human Hsp72 studies (P<0.0001 were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P<0.0001. Only human studies reported Hsp72-associated mortality (21.4% or infection (7.1% or reported results (14.3% to be nonprotective (P<0.001. In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%, compared to 57.1% of human studies (P<0.02, reduced proinflammatory cytokines (28/29, and enhanced survival (18/18. Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.

  3. Animal models for the study of leishmaniasis immunology.

    Science.gov (United States)

    Loría-Cervera, Elsy Nalleli; Andrade-Narváez, Fernando José

    2014-01-01

    Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers ("low" 1 × 10(2) and "high" 1 × 10(6)) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

  4. Postoperative pain management and proinflammatory cytokines: animal and human studies.

    Science.gov (United States)

    Shavit, Yehuda; Fridel, Keren; Beilin, Benzion

    2006-12-01

    The postoperative period is associated with neuroendocrine, metabolic, and immune alterations, which are the combined result of tissue damage, anesthesia, postoperative pain, and psychological stress. Limited evidence indicates that pain management in the postoperative period can affect the outcome of the surgery, reducing cardiac, pulmonary, and metabolic complications. Recent evidence indicates that pain and immune factors, especially proinflammatory cytokines, mutually interact and influence each other. A series of animal studies demonstrates that effective preemptive analgesia improved postoperative recovery, and this effect was enhanced by coadministration of IL-1ra together with the preemptive analgesics. Furthermore, preemptive analgesia attenuated surgery-induced PGE(2) production in the amygdala and the activation of the HPA axis. IL-1 signaling is required for the production of amygdala PGE(2) in response to surgical stress, and may thus affect the physiological and psychological aspects of surgical stress. These reports suggest that short-term effective analgesia can have long-lasting beneficial effects on surgery recovery. They further suggest that IL-1 blockade should be considered in the clinical management of pain associated with peripheral or nerve injury. Another series of human studies describes an interaction between the effectiveness of postoperative pain relief and surgery-associated immune alterations: In three separate studies, the more effective pain management technique was associated with diminished surgery-induced immune alterations, especially diminished elevation of IL-1. Reduced elevation of postoperative IL-1 and effective pain relief may both contribute to an attenuated illness response and a better surgery outcome.

  5. EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals

    DEFF Research Database (Denmark)

    Hald, Tine; Baggesen, Dorte Lau

    . Under natural exposure conditions, animals that are heterozygous or homozygous A136R154R171 display respectively a low or negligible risk of being infected. The genetic control of the susceptibility to classical scrapie is also likely to impact on the risk of transmitting the disease via embryo transfer......The risk of transmission of classical scrapie via the transfer of in vivo derived embryo in ovines was assessed, taking into account the scientific information made available since the last EFSA opinion on this topic (2010) (see http://www.efsa.europa.eu/en/efsajournal/pub/1429.htm). The potential...... impact of PrP genotype of the embryo and/or of the ram and donor ewe on this risk was also assessed. The new data made available over the last three years further reinforce the view that classical scrapie could be vertically transmitted in sheep. Since the possibility of such vertical transmission...

  6. Quantifying massive allograft healing of the canine femur in vivo and ex vivo: a pilot study.

    Science.gov (United States)

    Santoni, Brandon G; Ehrhart, Nicole; Betancourt-Benitez, Ricardo; Beck, Christopher A; Schwarz, Edward M

    2012-09-01

    Allograft integration in segmental osseous defects is unpredictable. Imaging techniques have not been applied to investigate angiogenesis and bone formation during allograft healing in a large-animal model. We used dynamic contrast-enhanced (DCE)-MRI and cone beam (CB)-CT to quantify vascularity and bone volume in a canine femoral allograft model and determined their relationship with biomechanical testing and histomorphometry. Femoral ostectomy was performed in three dogs and reconstructed with a 5-cm allograft and compression plate. At 0.5, 3, and 6 months, we performed DCE-MRI to quantify vascular permeability (Ktrans) and perfused fraction and CB-CT to quantify bone volume. We also performed posteuthanasia torsional testing and dynamic histomorphometry of the grafted and nonoperated femurs. DCE-MRI confirmed the avascular nature of allograft healing (perfused fraction, 2.08%-3.25%). CB-CT demonstrated new bone formation at 3 months (26.2, 3.7, and 2.2 cm(3)) at the graft-host junctions, which remodeled down at 6 months (14.0, 2.2, and 2.0 cm(3)). The increased bone volume in one subject was confirmed with elevated Ktrans (0.22) at 3 months. CB-CT-identified remodeled bone at 6 months was corroborated by histomorphometry. Allografted femurs recovered only 40% of their strength at 6 months. CB-CT and DCE-MRI can discriminate differences in angiogenesis and bone formation in the canine allograft model, which has potential to detect a small (32%) drug or device effect on biomechanical healing with only five animals per group.

  7. A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens.

    Science.gov (United States)

    Boettger-Tong, H; Murthy, L; Chiappetta, C; Kirkland, J L; Goodwin, B; Adlercreutz, H; Stancel, G M; Mäkelä, S

    1998-01-01

    We recently noted that immature rats failed to exhibit a normal uterine response to exogenously administered estradiol as assessed by both biochemical (induction of gene expression) and morphological (altered uterine and vaginal histology and size) end points. An initial analysis suggested that this was due to a high degree of estrogenization from a dietary source which was producing a near maximal uterotrophic response prior to hormone treatment. Subsequent chemical analysis indicated that the feed in question contained high amounts of two well-known phytoestrogens, genistein (210 mg/kg) and daidzen (14 mg/kg), and the lot of feed in question produced a large uterotrophic effect when fed to immature ovariectomized rats. These findings illustrate that, despite increased awareness of phytoestrogens, some batches of animal feed contain very high amounts of estrogenic components which have marked effects on in vivo end points of hormone action. These observations have important implications for both basic research and screening methods that utilize in vivo approaches. Images Figure 2 Figure 3 PMID:9637793

  8. In vivo x-ray phase contrast analyzer-based imaging for longitudinal osteoarthritis studies in guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Coan, Paola [Faculty of Medicine and Institute of Clinical Radiology, Ludwig-Maximilians University, Munich (Germany); Wagner, Andreas; Mollenhauer, Juergen [Department of Orthopaedics of the University of Jena, Rudolf-Elle-Hospital Eisenberg (Germany); Bravin, Alberto; Diemoz, Paul C; Keyrilaeinen, Jani, E-mail: Paola.Coan@physik.uni-muenchen.d [European Synchrotron Radiation Facility (ESRF), Grenoble (France)

    2010-12-21

    Over the last two decades phase contrast x-ray imaging techniques have been extensively studied for applications in the biomedical field. Published results demonstrate the high capability of these imaging modalities of improving the image contrast of biological samples with respect to standard absorption-based radiography and routinely used clinical imaging techniques. A clear depiction of the anatomic structures and a more accurate disease diagnosis may be provided by using radiation doses comparable to or lower than those used in current clinical methods. In the literature many works show images of phantoms and excised biological samples proving the high sensitivity of the phase contrast imaging methods for in vitro investigations. In this scenario, the applications of the so-called analyzer-based x-ray imaging (ABI) phase contrast technique are particularly noteworthy. The objective of this work is to demonstrate the feasibility of in vivo x-ray ABI phase contrast imaging for biomedical applications and in particular with respect to joint anatomic depiction and osteoarthritis detection. ABI in planar and tomographic modes was performed in vivo on articular joints of guinea pigs in order to investigate the animals with respect to osteoarthritis by using highly monochromatic x-rays of 52 keV and a low noise detector with a pixel size of 47 x 47 {mu}m{sup 2}. Images give strong evidence of the ability of ABI in depicting both anatomic structures in complex systems as living organisms and all known signs of osteoarthritis with high contrast, high spatial resolution and with an acceptable radiation dose. This paper presents the first proof of principle study of in vivo application of ABI. The technical challenges encountered when imaging an animal in vivo are discussed. This experimental study is an important step toward the study of clinical applications of phase contrast x-ray imaging techniques.

  9. In vivo x-ray phase contrast analyzer-based imaging for longitudinal osteoarthritis studies in guinea pigs

    Science.gov (United States)

    Coan, Paola; Wagner, Andreas; Bravin, Alberto; Diemoz, Paul C.; Keyriläinen, Jani; Mollenhauer, Juergen

    2010-12-01

    Over the last two decades phase contrast x-ray imaging techniques have been extensively studied for applications in the biomedical field. Published results demonstrate the high capability of these imaging modalities of improving the image contrast of biological samples with respect to standard absorption-based radiography and routinely used clinical imaging techniques. A clear depiction of the anatomic structures and a more accurate disease diagnosis may be provided by using radiation doses comparable to or lower than those used in current clinical methods. In the literature many works show images of phantoms and excised biological samples proving the high sensitivity of the phase contrast imaging methods for in vitro investigations. In this scenario, the applications of the so-called analyzer-based x-ray imaging (ABI) phase contrast technique are particularly noteworthy. The objective of this work is to demonstrate the feasibility of in vivo x-ray ABI phase contrast imaging for biomedical applications and in particular with respect to joint anatomic depiction and osteoarthritis detection. ABI in planar and tomographic modes was performed in vivo on articular joints of guinea pigs in order to investigate the animals with respect to osteoarthritis by using highly monochromatic x-rays of 52 keV and a low noise detector with a pixel size of 47 × 47 µm2. Images give strong evidence of the ability of ABI in depicting both anatomic structures in complex systems as living organisms and all known signs of osteoarthritis with high contrast, high spatial resolution and with an acceptable radiation dose. This paper presents the first proof of principle study of in vivo application of ABI. The technical challenges encountered when imaging an animal in vivo are discussed. This experimental study is an important step toward the study of clinical applications of phase contrast x-ray imaging techniques.

  10. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

    Science.gov (United States)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

    2016-08-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p animal research and a step towards a humanized in vivo model for tissue engineering.

  11. Genetic and ecological studies of animals in Chernobyl and Fukushima.

    Science.gov (United States)

    Mousseau, Timothy A; Møller, Anders P

    2014-01-01

    Recent advances in genetic and ecological studies of wild animal populations in Chernobyl and Fukushima have demonstrated significant genetic, physiological, developmental, and fitness effects stemming from exposure to radioactive contaminants. The few genetic studies that have been conducted in Chernobyl generally show elevated rates of genetic damage and mutation rates. All major taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers, dragonflies, spiders, mammals) displayed reduced population sizes in highly radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population censuses of birds, butterflies, and cicadas suggested that abundances were negatively impacted by exposure to radioactive contaminants, while other groups (e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines, at least during the first summer following the disaster. Insufficient information exists for groups other than insects and birds to assess effects on life history at this time. The differences observed between Fukushima and Chernobyl may reflect the different times of exposure and the significance of multigenerational mutation accumulation in Chernobyl compared to Fukushima. There was considerable variation among taxa in their apparent sensitivity to radiation and this reflects in part life history, physiology, behavior, and evolutionary history. Interestingly, for birds, population declines in Chernobyl can be predicted by historical mitochondrial DNA base-pair substitution rates that may reflect intrinsic DNA repair ability. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Qualichem In Vivo: A Tool for Assessing the Quality of In Vivo Studies and Its Application for Bisphenol A

    Science.gov (United States)

    Maxim, Laura; van der Sluijs, Jeroen P.

    2014-01-01

    In regulatory toxicology, quality assessment of in vivo studies is a critical step for assessing chemical risks. It is crucial for preserving public health studies that are considered suitable for regulating chemicals are robust. Current procedures for conducting quality assessments in safety agencies are not structured, clear or consistent. This leaves room for criticism about lack of transparency, subjective influence and the potential for insufficient protection provided by resulting safety standards. We propose a tool called “Qualichem in vivo” that is designed to systematically and transparently assess the quality of in vivo studies used in chemical health risk assessment. We demonstrate its use here with 12 experts, using two controversial studies on Bisphenol A (BPA) that played an important role in BPA regulation in Europe. The results obtained with Qualichem contradict the quality assessments conducted by expert committees in safety agencies for both of these studies. Furthermore, they show that reliance on standardized guidelines to ensure scientific quality is only partially justified. Qualichem allows experts with different disciplinary backgrounds and professional experiences to express their individual and sometimes divergent views—an improvement over the current way of dealing with minority opinions. It provides a transparent framework for expressing an aggregated, multi-expert level of confidence in a study, and allows a simple graphical representation of how well the study integrates the best available scientific knowledge. Qualichem can be used to compare assessments of the same study by different health agencies, increasing transparency and trust in the work of expert committees. In addition, it may be used in systematic evaluation of in vivo studies submitted by industry in the dossiers that are required for compliance with the REACH Regulation. Qualichem provides a balanced, common framework for assessing the quality of studies that may

  13. Protective coatings for intraocular wirelessly controlled microrobots for implantation: Corrosion, cell culture, and in vivo animal tests.

    Science.gov (United States)

    Pokki, Juho; Ergeneman, Olgaç; Chatzipirpiridis, George; Lühmann, Tessa; Sort, Jordi; Pellicer, Eva; Pot, Simon A; Spiess, Bernhard M; Pané, Salvador; Nelson, Bradley J

    2017-05-01

    Diseases in the ocular posterior segment are a leading cause of blindness. The surgical skills required to treat them are at the limits of human manipulation ability, and involve the risk of permanent retinal damage. Instrument tethering and design limit accessibility within the eye. Wireless microrobots suturelessly injected into the posterior segment, steered using magnetic manipulation are proposed for procedures involving implantation. Biocompatibility is a prerequisite for these procedures. This article investigates the use of polypyrrole- and gold-coated cobalt-nickel microrobots. While gold has been used in ocular implants, no ocular implantation involving polypyrrole is reported, despite its well-established biocompatibility properties. Coated and uncoated microrobots were investigated for their corrosion properties, and solutions that had contained coated and uncoated microrobots for one week were tested for cytotoxicity by monitoring NIH3T3 cell viability. None of the microrobots showed significant corrosion currents and corrosion potentials were as expected in relation to the intrinsic nobility of the materials. NIH3T3 cell viability was not affected by the release medium, in which coated/uncoated microrobots were stored. In vivo tests inside rabbit eyes were performed using coated microrobots. There were no significant inflammatory responses during the first week after injection. An inflammatory response detected after 2 weeks was likely due to a lack of longer-duration biocompatibility. The results provide valuable information for those who work on implant technology and biocompatibility. Coated microrobots have the potential to facilitate a new generation of surgical treatments, diagnostics and drug-delivery techniques, when implantation in the ocular posterior segment will be possible. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 836-845, 2017. © 2016 Wiley Periodicals, Inc.

  14. Small animals in the study of pathological effects of asbestos.

    Science.gov (United States)

    Holt, P F

    1974-12-01

    The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies. The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos. Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 mum long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to

  15. In vivo cerebral blood flow autoregulation studies using rheoencephalography

    Science.gov (United States)

    Bodo, M.; Pearce, F.; Garcia, A.; Van Albert, S.; Settle, T.; Szebeni, J.; Baranyi, L.; Hartings, J.; Armonda, R.

    2010-04-01

    Acute management of patients with traumatic brain/blast injury is a challenge. To minimize secondary injury and improve outcome, it is critical to detect neurological deterioration early, when it is potentially reversible. One potential monitoring method is cerebral electrical impedance (rheoencephalography-REG) because of its non-invasiveness and good time resolution. Reported here are the results of cerebral blood flow (CBF) manipulations comparing electroencephalogram (EEG) with REG (both intra-cerebral) and measuring with surface and skull REG electrodes. Our hypothesis was that REG would reflect spreading depression and CBF autoregulation. Animal experiments were performed using one rat (four trials with intracerebral electrodes), monkeys (n=8, with surface electrodes) and pigs (n = 24 pigs with skull electrodes; 57 trials, 19 types of liposomes). Challenges included intracranial pressure (ICP) elevation, liposome infusion, and hemorrhage. Data were stored on a PC and evaluated off line. CBF autoregulation was evaluated both by visual inspection and by a Matlab script. These studies confirmed that REG reflects CBF autoregulation and that REG is useful for detecting spreading depression (SD), vasospasm and the lower limit of CBF autoregulation. These findings have clinical relevance for use in noninvasive neuro-monitoring in the neurosurgery intensive care and during transportation of patients with brain injury.

  16. Antidepressant drugs and memory: insights from animal studies.

    Science.gov (United States)

    Monleón, Santiago; Vinader-Caerols, Concepción; Arenas, M Carmen; Parra, Andrés

    2008-04-01

    This is a selective review of the literature concerning the effects of antidepressant drugs on animal memory, which was performed with the aid of the PubMed database. Monoamine oxidase inhibitors tend to either have no effect on memory or result in its improvement. Studies with cyclic antidepressants have reported no effect or, more often, memory impairments. Pre-training administration of selective serotonin reuptake inhibitors (SSRIs) has been shown to have either no effect on memory or undermine it (with some isolated exceptions, in which improvements have been recorded), while post-training administration of SSRIs has been demonstrated to improve memory or have no effect. A small group formed by the remaining antidepressants has been shown to improve memory, with the exception of trazodone, which impairs memory. These findings are discussed in the light of knowledge regarding the actions of antidepressants on several neurotransmission systems. The possibility that the effects of antidepressants on memory are the core of the therapeutic effects of these drugs is also considered.

  17. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Elsy Nalleli Loria-Cervera

    2014-01-01

    Full Text Available Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail are being infected, and different numbers (“low” 1×102 and “high” 1×106 of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

  18. Studies on animal schistosomes in Peninsular Malaysia: record of naturally infected animals and additional hosts of Schistosoma spindale.

    Science.gov (United States)

    Inder Singh, K; Krishnasamy, M; Ambu, S; Rasul, R; Chong, N L

    1997-06-01

    Surveillance studies on cercarial dermatitis were carried out in paddy growing areas in Peninsular Malaysia. It was observed that dermatitis in paddy planters occurred in paddy fields which were cultivated using animals such as bafflos or fields where domestic animals were allowed to graze during the off planting season as these animals harbored the parasite. The causative agent of cercarial dermatitis was Schistosoma spindale. A total of 215 small mammals trapped from Alor Setar and 126 trapped from Labu were examined for the schistosome. In Alor Setar Bandicota indica, Rattus argentiventer and Rattus rattus diardii were the only wild mammals found to be infected with the parasite, while in the Labu areas only Rattus tiomanicus jalorensis was positive for the schistosome. The occurrence of S. spindale in R. argentiventer and R.r. diardii in Alor Setar and in R.t. jalorensis in Labu constitute new host and geographic distribution records of the schistosome.

  19. Animal health economics: an aid to decisionmaking on animal health interventions - case studies in the United States of America.

    Science.gov (United States)

    Marsh, T L; Pendell, D; Knippenberg, R

    2017-04-01

    For animal disease events the outcomes and consequences often remain unclear or uncertain, including the expected changes in benefits (e.g. profit to firms, prices to consumers) and in costs (e.g. response, clean-up). Moreover, the measurement of changes in benefits and costs across alternative interventions used to control animal disease events may be inexact. For instance, the economic consequences of alternative vaccination strategies to mitigate a disease can vary in magnitude due to trade embargoes and other factors. The authors discuss the economic measurement of animal disease outbreaks and interventions and how measurement is used in private and public decision-making. Two illustrative case studies in the United States of America are provided: a hypothetical outbreak of foot and mouth disease in cattle, and the 2014-2015 outbreak of highly pathogenic avian influenza in poultry.

  20. Effect of lung flooding and high-intensity focused ultrasound on lung tumours: an experimental study in an ex vivo human cancer model and simulated in vivo tumours in pigs.

    Science.gov (United States)

    Wolfram, Frank; Boltze, Carsten; Schubert, Harald; Bischoff, Sabine; Lesser, Thomas Günther

    2014-01-07

    High-intensity focused ultrasound is a valuable tool for minimally invasive tumour ablation. However, due to the air content in ventilated lungs, lung tumours have never been treated with high-intensity focused ultrasound. Lung flooding enables efficient lung sonography and tumour imaging in ex vivo human and in vivo porcine lung cancer models. The current study evaluates the effectiveness of lung flooding and sonography-guided high-intensity focused ultrasound for lung tumour ablation in ex vivo human and in vivo animal models. Lung flooding was performed in four human lung lobes which were resected from non-small cell lung cancers. B-mode imaging and temperature measurements were simultaneously obtained during high-intensity focused ultrasonography of centrally located lung cancers. The tumour was removed immediately following insonation and processed for nicotinamide adenine dinucleotide phosphate-diaphorase and H&E staining. In addition, the left lungs of three pigs were flooded. Purified BSA in glutaraldehyde was injected centrally into the left lower lung lobe to simulate a lung tumour. The ultrasound was focused transthoracically through the flooded lung into the simulated tumour with the guidance of sonography. The temperature of the tumour was simultaneously measured. The vital signs of the animal were monitored during the procedure. A well-demarcated lesion of coagulation necrosis was produced in four of four human lung tumours. There did not appear to be any damage to the surrounding lung parenchyma. After high-intensity focused ultrasound insonation, the mean temperature increase was 7.5-fold higher in the ex vivo human tumour than in the flooded lung tissue (52.1 K ± 8.77 K versus 7.1 K ± 2.5 K). The transthoracic high-intensity focused ultrasound of simulated tumours in the in vivo model resulted in a mean peak temperature increase up to 53.7°C (±4.5). All of the animals survived the procedure without haemodynamic complications. High

  1. Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yanming [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States)], E-mail: yanming.wang@case.edu; Liu Lili [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Wu Chunying [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Bulgar, Alina [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Somoza, Eduardo; Zhu Wenxia [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Gerson, Stanton L. [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States)

    2009-11-15

    Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([{sup 11}C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [{sup 11}C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [{sup 11}C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [{sup 11}C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.

  2. In vivo studies to highlight possible illegal treatments of rabbits with carbadox and olaquindox.

    Science.gov (United States)

    Segato, Giulia; Biancotto, Giancarlo; Agnoletti, Fabrizio; Berto, Giacomo; Montesissa, Clara; Benetti, Cristiana

    2015-01-01

    For the treatment of rabbit dysentery and bacterial enteritis, veterinary practitioners often adopt veterinary medicinal products authorised for other food-producing species, but in some cases non-authorised drugs frequently used in the past, such as carbadox and olaquindox, might be illegally adopted. To verify the carbadox and olaquindox distribution and persistence in rabbit tissues, two independent in vivo studies were carried out. In the first study, 24 healthy rabbits received water medicated with carbadox at 100 mg l(-1) over a period 28 days, whereas in the second one, 24 healthy rabbits were administered water containing olaquindox at 100 mg l(-1). In each study rabbits were randomly assigned to four groups to be sacrificed respectively at 0, 5, 10 and 20 days from treatment withdrawal, for depletion studies. A control group of six animals was adopted for control and as a reservoir of blank tissues. Muscle and liver samples collected from each treated animal were stored at -20°C pending the analysis. Sensitive and robust liquid chromatography-tandem mass spectrometry analytical methods were set up for the parent compounds and their main metabolites quinoxaline-2-carboxylic acid, desoxycarbadox and 3-methylquinoxaline-2-carboxylic acid to verify their residual. Data collected demonstrate that the combination of liver as target matrix, quinoxaline-2-carboxylic acid and 3-methylquinoxaline-2-carboxylic acid as marker residue and enzymatic digestion is strategic to evidence carbadox and/or olaquindox illegal treatments in rabbits, even 20 days after treatment withdrawal at concentration levels higher than 0.5 µg kg(-1). This findings suggests that liver should be proposed as target matrix for official control in national monitoring plan.

  3. Study on establishment of esophageal carcinoma animal models

    Directory of Open Access Journals (Sweden)

    ZHAO Qiang

    2013-08-01

    Full Text Available Esophageal cancer is one of the common human gastrointestinal malignancies.In recent years,the global incidence of esophageal cancer and its mortality rise.China is the high incidence area of esophageal cancer with the highest morbidity and mortality in the world.However,the exact pathogeny of esophageal cancer has not been fully clarified yet.Thus,it is of significant importance to establish ideal and stable esophageal carcinoma animal models with similar biological characteristics to clinical tumors,which will provide a reliable research basis for the occurrence,development,metastasis and drug responses of esophageal carcinoma,and is also helpful for anti-esophageal cancer drug screening and the development of rational dinical therapeutic treatment.This article provides an overview of the development of esophageal carcinoma animal models in recent years,the classification of esophageal carcinoma animal models,modeling methods and the progress of model evaluation.

  4. In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract

    Science.gov (United States)

    Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

    2016-01-01

    Background: Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. Objective: The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). Materials and Methods: The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. Results: The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. Conclusion: The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. SUMMARY Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening

  5. In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract.

    Science.gov (United States)

    Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

    2016-01-01

    Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening test in mice and Rota-.rod test.The GABAergic system plays a significant role

  6. Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

    Science.gov (United States)

    Asic, Adna; Kurtovic-Kozaric, Amina; Besic, Larisa; Mehinovic, Lejla; Hasic, Azra; Kozaric, Mirza; Hukic, Mirsada; Marjanovic, Damir

    2017-07-01

    The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Utility of a human-mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing.

    Science.gov (United States)

    Shanmugam, Victoria K; Tassi, Elena; Schmidt, Marcel O; McNish, Sean; Baker, Stephen; Attinger, Christopher; Wang, Hong; Shara, Nawar; Wellstein, Anton

    2015-12-01

    To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  8. Animal experimentation in Japan: regulatory processes and application for microbiological studies.

    Science.gov (United States)

    Takahashi-Omoe, H; Omoe, K

    2007-07-01

    We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan.

  9. Vascular targets for cannabinoids: animal and human studies

    Science.gov (United States)

    Stanley, Christopher; O'Sullivan, Saoirse E

    2014-01-01

    Application of cannabinoids and endocannabinoids to perfused vascular beds or individual isolated arteries results in changes in vascular resistance. In most cases, the result is vasorelaxation, although vasoconstrictor responses are also observed. Cannabinoids also modulate the actions of vasoactive compounds including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane mimetic). Numerous mechanisms of action have been proposed including receptor activation, potassium channel activation, calcium channel inhibition and the production of vasoactive mediators such as calcitonin gene-related peptide, prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen peroxide. The purpose of this review is to examine the evidence for the range of receptors now known to be activated by cannabinoids. Direct activation by cannabinoids of CB1, CBe, TRPV1 (and potentially other TRP channels) and PPARs in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1A has also been identified in some studies. Indirectly, activation of prostanoid receptors (TP, IP, EP1 and EP4) and the CGRP receptor is involved in the vascular responses to cannabinoids. The majority of this evidence has been obtained through animal research, but recent work has confirmed some of these targets in human arteries. Vascular responses to cannabinoids are enhanced in hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to changes in the target sites of action. Much further work is required to establish the extent of vascular actions of cannabinoids and the application of this research in physiological and pathophysiological situations. Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6 PMID:24329566

  10. The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

    Science.gov (United States)

    Infants and children with tuberculosis (TB) account for more than 20% of cases in endemic countries. Current animal models study TB during adulthood but animal models for adolescent and infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and ...

  11. Why animal studies are still being used in drug development. An innovation system perspective

    NARCIS (Netherlands)

    Kooijman, M.

    2013-01-01

    In Europe alone, 3.6 million animals per year are used for drug development. Animal studies are worldwide the gold standard to evaluate the safety, efficacy and quality of drugs before these drugs are tested in humans. Nevertheless the value of animal studies to predict risks for humans has never

  12. In vivo study of lens regeneration in Rana cyanophlyctis under ...

    African Journals Online (AJOL)

    Vitamin A and ascorbic acid enhanced the percentage lens regeneration not only in young tadpoles but also in froglets. Lens regeneration ability declined with age of animals in both control as well as treated groups. Keywords: Rana cyanophlyctis, pigmented epithelial cells, vitamin A, ascorbic acid. African Journal of ...

  13. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

    Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which ...

  14. Markerless 3D motion capture for animal locomotion studies

    Directory of Open Access Journals (Sweden)

    William Irvin Sellers

    2014-06-01

    Full Text Available Obtaining quantitative data describing the movements of animals is an essential step in understanding their locomotor biology. Outside the laboratory, measuring animal locomotion often relies on video-based approaches and analysis is hampered because of difficulties in calibration and often the limited availability of possible camera positions. It is also usually restricted to two dimensions, which is often an undesirable over-simplification given the essentially three-dimensional nature of many locomotor performances. In this paper we demonstrate a fully three-dimensional approach based on 3D photogrammetric reconstruction using multiple, synchronised video cameras. This approach allows full calibration based on the separation of the individual cameras and will work fully automatically with completely unmarked and undisturbed animals. As such it has the potential to revolutionise work carried out on free-ranging animals in sanctuaries and zoological gardens where ad hoc approaches are essential and access within enclosures often severely restricted. The paper demonstrates the effectiveness of video-based 3D photogrammetry with examples from primates and birds, as well as discussing the current limitations of this technique and illustrating the accuracies that can be obtained. All the software required is open source so this can be a very cost effective approach and provides a methodology of obtaining data in situations where other approaches would be completely ineffective.

  15. Open Science and Reporting Animal Studies: Who's Accountable?

    OpenAIRE

    Eisen, JA; Ganley, E; MacCallum, CJ

    2014-01-01

    If being open means maximizing the number of people a paper can reach and minimizing the difficulties of re-using the information within it, then the release of all information associated with a paper is critical. For ethical reasons, high standards of reporting are extra critical in regards to animal research.

  16. Transscleral diffusion of carboplatin: an in vitro and in vivo study.

    Science.gov (United States)

    Simpson, Amanda E; Gilbert, Jake A; Rudnick, David E; Geroski, Dayle H; Aaberg, Thomas M; Edelhauser, Henry F

    2002-08-01

    To compare the in vitro scleral permeability of carboplatin using either a fibrin sealant or a balanced salt solution (BSS) vehicle and to measure in vivo ocular tissue levels following subconjunctival injection of carboplatin in fibrin sealant or BSS. The permeability of carboplatin in fibrin sealant or BSS through human eye bank sclera was tested using an in vitro perfusion apparatus. Levels of carboplatin permeating the sclera were measured every hour for 24 hours using atomic absorption spectrometry. In vivo studies were performed in Dutch Belted rabbits injected subconjunctivally with carboplatin in either fibrin sealant or BSS; eyes were enucleated at 1(1/2) hours, 48 hours, and 2 weeks after injection, and levels of carboplatin were measured in various tissues. In vitro carboplatin in fibrin sealant had a peak permeability constant of 13.7 +/- 2.3 x 10(-6) cm/s; carboplatin in BSS, 27.0 +/- 1.7 x 10(-6) cm/s. After 24 hours, 33.2% +/- 1.8% of the carboplatin was retained in the fibrin sealant, while 5.5% +/- 1.0% was retained in the BSS. In vivo subconjunctival injection of carboplatin in fibrin sealant vehicle achieved 11.83 +/- 5.16 microg/mL in the vitreous at 1(1/2) hours and 0.03 +/- 0.06 microg/mL in the vitreous at 2 weeks. The fibrin sealant also attained 396.59 +/- 177.84 microg/mg in the choroid and retina at 1(1/2) hours and 3.38 +/- 1.97 microg/mg in the choroid and retina at 2 weeks. (Data are given as mean +/- SEM.) Fibrin sealant provided a more controlled and localized release of carboplatin and delivered carboplatin to the ocular tissues for up to 2 weeks. This study reports the use of fibrin sealant as a subconjunctival delivery vehicle for carboplatin, and quantifies ocular drug levels achieved in an animal model.

  17. Gnotobiotic rodents: an in vivo model to study microbe-microbe interactions

    Directory of Open Access Journals (Sweden)

    Rebeca eMartin

    2016-03-01

    Full Text Available Germ-free rodents have no microorganisms living in or on them, allowing researchers to specifically control an animal’s microbiota through the direct inoculation of bacteria of interest. This strategy has been widely used to decipher host-microbe interactions as well as the role of microorganisms in both i the development and function of the gut barrier (mainly the intestinal epithelium and ii homeostasis and its effects on human health and disease. However, this in vivo model also offers a more realistic environment than an assay tube in which to study microbe-microbe interactions, without most of the confounding interactions present in the intestinal microbiota of conventionally raised mice. This review highlights the usefulness of controlled-microbiota mice in studying microbe-microbe interactions. To this end, we summarize current knowledge on germ-free animals as an experimental model for the study of the ecology and metabolism of intestinal bacteria as well as of microbe-microbe interactions.

  18. The isolated perfused equine distal limb as an ex vivo model for pharmacokinetic studies.

    Science.gov (United States)

    Friebe, M; Stahl, J; Kietzmann, M

    2013-06-01

    Even though intra-articular injections play an important role in the treatment of joint-related lameness in horses, little is known about pharmacokinetic properties of substances used. Therefore, an ex vivo model for pharmacokinetic studies was developed using distal forelimbs of slaughtered horses. The extremity was perfused with gassed Tyrode solution for up to 8 h. Tissue viability was confirmed by measurements of glucose consumption, lactate production, and lactate dehydrogenase activity in the perfusate. Standard criteria for tissue viability had been determined in preliminary experiments (n = 11), which also included histological examinations of the joint capsule. As the model's first implementation, the articular efflux rate of betamethasone (BM), administered as BM disodium phosphate intra-articularly to the fetlock joint (4 mg BM/joint), was investigated. The concentration of BM in the venous perfusate of the radial vein was measured by means of high-performance liquid chromatography. The average BM efflux rate per minute was calculated to be 5.1 μg/min with values ranging from 9 μg/min to 2.9 μg/min. 7.5 h after i.a. application, 2.3 mg BM had left the joint via the radial vein. Using this inexpensive setup, the presented model allows studying a variety of pharmacological topics without the ethical limitations of animal studies. © 2012 Blackwell Publishing Ltd.

  19. Application of tetra-isopalmitoyl ascorbic acid in cosmetic formulations: stability studies and in vivo efficacy.

    Science.gov (United States)

    Maia Campos, Patrícia M B G; Gianeti, Mirela D; Camargo, Flávio B; Gaspar, Lorena R

    2012-11-01

    Liposoluble vitamin C derivatives, such as tetra-isopalmitoyl ascorbic acid (IPAA), are often used in dermocosmetic products due to their higher stability than vitamin C free form as well as its proposed effects in skin; however, there are no studies analyzing IPAA stability or its in vivo effects when present in dermocosmetic formulations. Thus, this study aimed to evaluate chemical stability and pre-clinical and clinical efficacy of dermocosmetic formulations containing IPAA in skin hydration and microrelief. Chemical stability of the formulations added with 1% IPAA was evaluated by heat stress during 35 days by HPLC. For pre-clinical evaluation, experimental formulations were topically applied on hairless skin mice during 5 days and animal skins were analyzed by non-invasive biophysic techniques (water content of stratum corneum, TEWL, viscoelasticity, and microrelief) and by histopathological studies. For clinical efficacy tests, the formulations were topically applied to the forearm and face of human volunteers, and 3h and 15 days after applications, the skins were evaluated by the same non-invasive techniques mentioned before. Results showed that formulations containing IPAA had medium stability and had pronounced moisturizing effects on stratum corneum and on viable epidermis. These formulations also improved skin microrelief especially in relation to skin smoothness and roughness. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Simple models for studying complex spatiotemporal patterns of animal behavior

    Science.gov (United States)

    Tyutyunov, Yuri V.; Titova, Lyudmila I.

    2017-06-01

    Minimal mathematical models able to explain complex patterns of animal behavior are essential parts of simulation systems describing large-scale spatiotemporal dynamics of trophic communities, particularly those with wide-ranging species, such as occur in pelagic environments. We present results obtained with three different modelling approaches: (i) an individual-based model of animal spatial behavior; (ii) a continuous taxis-diffusion-reaction system of partial-difference equations; (iii) a 'hybrid' approach combining the individual-based algorithm of organism movements with explicit description of decay and diffusion of the movement stimuli. Though the models are based on extremely simple rules, they all allow description of spatial movements of animals in a predator-prey system within a closed habitat, reproducing some typical patterns of the pursuit-evasion behavior observed in natural populations. In all three models, at each spatial position the animal movements are determined by local conditions only, so the pattern of collective behavior emerges due to self-organization. The movement velocities of animals are proportional to the density gradients of specific cues emitted by individuals of the antagonistic species (pheromones, exometabolites or mechanical waves of the media, e.g., sound). These cues play a role of taxis stimuli: prey attract predators, while predators repel prey. Depending on the nature and the properties of the movement stimulus we propose using either a simplified individual-based model, a continuous taxis pursuit-evasion system, or a little more detailed 'hybrid' approach that combines simulation of the individual movements with the continuous model describing diffusion and decay of the stimuli in an explicit way. These can be used to improve movement models for many species, including large marine predators.

  1. Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates.

    Directory of Open Access Journals (Sweden)

    Sitara S R Ajjampur

    Full Text Available Blastocystis spp. are widely prevalent extra cellular, non-motile anerobic protists that inhabit the gastrointestinal tract. Although Blastocystis spp. have been associated with gastrointestinal symptoms, irritable bowel syndrome and urticaria, their clinical significance has remained controversial. We established an ex vivo mouse explant model to characterize adhesion in the context of tissue architecture and presence of the mucin layer. Using confocal microscopy with tissue whole mounts and two axenic isolates of Blastocystis spp., subtype 7 with notable differences in adhesion to intestinal epithelial cells (IEC, isolate B (ST7-B and isolate H (more adhesive, ST7-H, we showed that adhesion is both isolate dependent and tissue trophic. The more adhesive isolate, ST7-H was found to bind preferentially to the colon tissue than caecum and terminal ileum. Both isolates were also found to have mucinolytic effects. We then adapted a DSS colitis mouse model as a susceptible model to study colonization and acute infection by intra-caecal inoculation of trophic Blastocystis spp.cells. We found that the more adhesive isolate ST7-H was also a better colonizer with more mice shedding parasites and for a longer duration than ST7-B. Adhesion and colonization was also associated with increased virulence as ST7-H infected mice showed greater tissue damage than ST7-B. Both the ex vivo and in vivo models used in this study showed that Blastocystis spp. remain luminal and predominantly associated with mucin. This was further confirmed using colonic loop experiments. We were also successfully able to re-infect a second batch of mice with ST7-H isolates obtained from fecal cultures and demonstrated similar histopathological findings and tissue damage thereby coming closer to proving Koch's postulates for this parasite.

  2. Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates.

    Science.gov (United States)

    Ajjampur, Sitara S R; Png, Chin Wen; Chia, Wan Ni; Zhang, Yongliang; Tan, Kevin S W

    2016-01-01

    Blastocystis spp. are widely prevalent extra cellular, non-motile anerobic protists that inhabit the gastrointestinal tract. Although Blastocystis spp. have been associated with gastrointestinal symptoms, irritable bowel syndrome and urticaria, their clinical significance has remained controversial. We established an ex vivo mouse explant model to characterize adhesion in the context of tissue architecture and presence of the mucin layer. Using confocal microscopy with tissue whole mounts and two axenic isolates of Blastocystis spp., subtype 7 with notable differences in adhesion to intestinal epithelial cells (IEC), isolate B (ST7-B) and isolate H (more adhesive, ST7-H), we showed that adhesion is both isolate dependent and tissue trophic. The more adhesive isolate, ST7-H was found to bind preferentially to the colon tissue than caecum and terminal ileum. Both isolates were also found to have mucinolytic effects. We then adapted a DSS colitis mouse model as a susceptible model to study colonization and acute infection by intra-caecal inoculation of trophic Blastocystis spp.cells. We found that the more adhesive isolate ST7-H was also a better colonizer with more mice shedding parasites and for a longer duration than ST7-B. Adhesion and colonization was also associated with increased virulence as ST7-H infected mice showed greater tissue damage than ST7-B. Both the ex vivo and in vivo models used in this study showed that Blastocystis spp. remain luminal and predominantly associated with mucin. This was further confirmed using colonic loop experiments. We were also successfully able to re-infect a second batch of mice with ST7-H isolates obtained from fecal cultures and demonstrated similar histopathological findings and tissue damage thereby coming closer to proving Koch's postulates for this parasite.

  3. Laser welding to assist penetrating keratoplasty: in vivo studies

    Science.gov (United States)

    Menabuoni, Luca; Mincione, F.; Mincione, G. P.; Pini, Roberto

    1998-01-01

    Laser-induced corneal welding has been tested in vivo to perform experimental trials of penetrating keratoplasty (corneal transplantation). Twenty rabbits of 2500 - 3500 g in weight were selected to undergo laser-assisted corneal transplantation and then subjected to follow up on 2 - 15 postoperative days. Good sealing along the entire cut length was obtained soon after the surgical operation. Histology examinations evidenced that the laser-assisted surgical procedure provides a satisfactory healing process of corneal tissue in times that are substantially shorter than those of the conventional procedure.

  4. Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem/stromal cells: present and future.

    Science.gov (United States)

    Astori, Giuseppe; Amati, Eliana; Bambi, Franco; Bernardi, Martina; Chieregato, Katia; Schäfer, Richard; Sella, Sabrina; Rodeghiero, Francesco

    2016-07-13

    The use of fetal bovine serum (FBS) as a cell culture supplement is discouraged by regulatory authorities to limit the risk of zoonoses and xenogeneic immune reactions in the transplanted host. Additionally, FBS production came under scrutiny due to animal welfare concerns. Platelet derivatives have been proposed as FBS substitutes for the ex-vivo expansion of mesenchymal stem/stromal cells (MSCs) since platelet-derived growth factors can promote MSC ex-vivo expansion. Platelet-derived growth factors are present in platelet lysate (PL) obtained after repeated freezing-thawing cycles of the platelet-rich plasma or by applying physiological stimuli such as thrombin or CaCl2.PL-expanded MSCs have been used already in the clinic, taking advantage of their faster proliferation compared with FBS-expanded preparations. Should PL be applied to other biopharmaceutical products, its demand is likely to increase dramatically. The use of fresh platelet units for the production of PL raises concerns due to limited availability of platelet donors. Expired units might represent an alternative, but further data are needed to define safety, including pathogen reduction, and functionality of the obtained PL. In addition, relevant questions concerning the definition of PL release criteria, including concentration ranges of specific growth factors in PL batches for various clinical indications, also need to be addressed. We are still far from a common definition of PL and standardized PL manufacture due to our limited knowledge of the mechanisms that mediate PL-promoting cell growth. Here, we concisely discuss aspects of PL as MSC culture supplement as a preliminary step towards an agreed definition of the required characteristics of PL for the requirements of manufacturers and users.

  5. Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab.

    Science.gov (United States)

    Honickel, Markus; Treutler, Stefanie; van Ryn, Joanne; Tillmann, Sabine; Rossaint, Rolf; Grottke, Oliver

    2015-04-01

    Urgent surgery or life-threatening bleeding requires prompt reversal of the anticoagulant effects of dabigatran. This study assessed the ability of three- and four-factor prothrombin complex concentrate (PCC) and idarucizumab (specific antidote for dabigatran) to reverse the anticoagulant effects of dabigatran in a porcine model of trauma. Twelve animals were given dabigatran etexilate (DE) orally and dabigatran intravenously, before infliction of trauma. Six animals received tranexamic acid plus fibrinogen concentrate 12 minutes post-injury. Six PCCs (each 30 and 60 U/kg) and idarucizumab (30 and 60 mg/kg) were added to blood samples ex vivo. Coagulation was assessed by several coagulation assays. All coagulation parameters were altered after dabigatran infusion (plasma level: 442 ± 138 ng/ml). Both three- and four-factor PCCs mostly or completely reversed the effects of dabigatran on thromboelastometry variables and PT but not on aPTT. Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the effects of the drug on coagulation variables. Thrombin generation showed dose-dependent over-correction following the addition of PCC, implying that elevated levels of thrombin are required to overcome dabigatran-induced coagulopathy. In contrast, treatment with idarucizumab returned thrombin generation to baseline levels. Following trauma, therapy with tranexamic acid plus fibrinogen improved correction of coagulation parameters by PCC, and thromboelastometry parameters by idarucizumab. All investigated PCCs improved dabigatran- and trauma-induced coagulopathy to a similar degree. In conclusion, this study shows that three- and four-factor PCCs are similarly effective for dabigatran reversal. Idarucizumab also reversed the effects of dabigatran and, unlike PCCs, was not associated with over-correction of thrombin generation.

  6. Androgen receptors and experimental bone loss - an in vivo and in vitro study.

    Science.gov (United States)

    Steffens, Joao Paulo; Coimbra, Leila Santana; Rossa, Carlos; Kantarci, Alpdogan; Van Dyke, Thomas E; Spolidorio, Luis Carlos

    2015-12-01

    Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1-orchiectomy (OCX); 2-OCX sham surgery; or 3-OCX sham surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1β production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor. Copyright © 2015 Elsevier Inc. All rights

  7. A novel method for cerebrospinal fluid diversion: a cadaveric and animal study.

    Science.gov (United States)

    Tubbs, R Shane; Bauer, David; Chambers, M Renee; Loukas, Marios; Shoja, Mohammadali M; Cohen-Gadol, Aaron A

    2011-02-01

    Cerebrospinal fluid (CSF) diversionary methods are fraught with complications (eg, infection, obstruction, and CSF malabsorption at the distal site). The authors investigated the sternum, specifically the manubrium, as a potential CSF receptacle for patients with hydrocephalus. Five fresh adult human cadavers had the manubrium cannulated in a suprasternal location. Tap water was infused via a metal trocar for approximately 60 minutes. Additionally, morphometric examination of the manubrium from 40 adult human skeletons was performed. Next, 4 anesthetized rhesus monkeys underwent cannulation of the manubrium: 2 were infused with 50 mL of saline over approximately 1 hour, and 2 were infused by gravity drip of saline over 24 hours. Finally, 2 adult pigs underwent long-term ventriculosternal tube placement with analysis for function and potential development of osteomyelitis. Thirty liters of water were injected into all cadaveric specimens without overflow or noticeable edema. No fluid accumulation was identified. The manubrium had a mean length, width, and thickness of 5.1 cm, 5.0 cm, and 1 cm, respectively. The animals that underwent infusion of 50 mL of saline and the animals that underwent gravity drip tolerated the procedure without vital sign changes or evidence of saline leakage into the pleural cavity. The 2 pigs did not show any vital sign changes, and, 2 weeks post procedure, they had no findings of osteomyelitis. Based on our studies, the manubrium of the sternum appears to be an ideal location for the placement of the distal end of a CSF diversionary shunt when other anatomic receptacles are not an option. In vivo human studies are now required to verify our findings.

  8. Meta-Analyses of Animal Studies: An Introduction of a Valuable Instrument to Further Improve Healthcare

    Science.gov (United States)

    Hooijmans, Carlijn R.; IntHout, Joanna; Ritskes-Hoitinga, Merel; Rovers, Maroeska M.

    2014-01-01

    In research aimed at improving human health care, animal studies still play a crucial role, despite political and scientific efforts to reduce preclinical experimentation in laboratory animals. In animal studies, the results and their interpretation are not always straightforward, as no single study is executed perfectly in all steps. There are several possible sources of bias, and many animal studies are replicates of studies conducted previously. Use of meta-analysis to combine the results of studies may lead to more reliable conclusions and a reduction of unnecessary duplication of animal studies. In addition, due to the more exploratory nature of animal studies as compared to clinical trials, meta-analyses of animal studies have greater potential in exploring possible sources of heterogeneity. There is an abundance of literature on how to perform meta-analyses on clinical data. Animal studies, however, differ from clinical studies in some aspects, such as the diversity of animal species studied, experimental design, and study characteristics. In this paper, we will discuss the main principles and practices for meta-analyses of experimental animal studies. PMID:25541544

  9. The Combination of In vivo (124)I-PET and CT Small Animal Imaging for Evaluation of Thyroid Physiology and Dosimetry.

    Science.gov (United States)

    El-Ali, Henrik H; Eckerwall, Martin; Skovgaard, Dorthe; Larsson, Erik; Strand, Sven-Erik; Kjaer, Andreas

    2012-06-05

    A thyroid rat model combining functional and anatomical information would be of great benefit for better modeling of thyroid physiology and for absorbed dose calculations. Our aim was to show that (124)I-PET and CT small animal imaging are useful as a combined model for studying thyroid physiology and dose calculation. Seven rats were subjects for multiple thyroid (124)I-imaging and CT-scans. S-values [mGy/MBqs] for different thyroid sizes were simulated. A phantom with spheres was designed for validation of performances of the small animal PET and CT imaging systems. Small animal image-based measurements of the activity amount and the volumes of the spheres with a priori known volumes showed a good agreement with their corresponding actual volumes. The CT scans of the rats showed thyroid volumes from 34-70 mL. The wide span in volumes of thyroid glands indicates the importance of using an accurate volume-measuring technique such as the small animal CT. The small animal PET system was on the other hand able to accurately estimate the activity concentration in the thyroid volumes. We conclude that the combination of the PET and CT image information is essential for quantitative thyroid imaging and accurate thyroid absorbed dose calculation.

  10. The Combination of In vivo 124I-PET and CT Small Animal Imaging for Evaluation of Thyroid Physiology and Dosimetry

    Science.gov (United States)

    El-Ali, Henrik H.; Eckerwall, Martin; Skovgaard, Dorthe; Larsson, Erik; Strand, Sven-Erik; Kjaer, Andreas

    2012-01-01

    Objective:A thyroid rat model combining functional and anatomical information would be of great benefit for better modeling of thyroid physiology and for absorbed dose calculations. Our aim was to show that 124I-PET and CT small animal imaging are useful as a combined model for studying thyroid physiology and dose calculation. Methods: Seven rats were subjects for multiple thyroid 124I-imaging and CT-scans. S-values [mGy/MBqs] for different thyroid sizes were simulated. A phantom with spheres was designed for validation of performances of the small animal PET and CT imaging systems. Results:Small animal image-based measurements of the activity amount and the volumes of the spheres with a priori known volumes showed a good agreement with their corresponding actual volumes. The CT scans of the rats showed thyroid volumes from 34–70 mL. Conclusions:The wide span in volumes of thyroid glands indicates the importance of using an accurate volume-measuring technique such as the small animal CT. The small animal PET system was on the other hand able to accurately estimate the activity concentration in the thyroid volumes. We conclude that the combination of the PET and CT image information is essential for quantitative thyroid imaging and accurate thyroid absorbed dose calculation. PMID:26859394

  11. American animation VS. Japanese Animation

    OpenAIRE

    Olsen, Stian; Johnsen, Frank

    2012-01-01

    This bachelor thesis is a comparative study between American animation and Japanese animation. We take a look into differences, taking into account the culture, history, production- and the animation techniques employed. The main theoretical questions that are answered in this study are: - How has each side of animation influenced the culture surrounding it, and vice versa? -Why can Japanese animation studios presumably produce more than twice the amount that an American animation studio p...

  12. In vivo copper-mediated free radical production: an ESR spin-trapping study

    Science.gov (United States)

    Kadiiska, Maria B.; Mason, Ronald P.

    2002-04-01

    Copper has been suggested to facilitate oxidative tissue injury through a free radical-mediated pathway analogous to the Fenton reaction. By applying the electron spin resonance (ESR) spin-trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid or paraquat. A secondary radical spin-trapping technique was used in which the hydroxyl radical formed the methyl radical upon reaction with dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap phenyl- N- t-butyl- nitrone (PBN). In contrast, lipid derived radical was detected in vivo in copper-challenged, vitamin E and selenium-deficient rats. These findings support the proposal that dietary selenium and vitamin E can protect against lipid peroxidation and copper toxicity. Since copper excreted into the bile from treated animals is expected to be maintained in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that would redox-stablilize it in the Cu(I) state was used to prevent ex vivo redox chemistry. Bile samples were collected directly into solutions of bathocuproinedisulfonic acid, a Cu(I)-stabilizing agent, and 2,2'-dipyridyl, a Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts generated ex vivo could be mistaken for radical adducts produced in vivo and excreted into the bile.

  13. The Combination of In vivo (124)I-PET and CT Small Animal Imaging for Evaluation of Thyroid Physiology and Dosimetry

    DEFF Research Database (Denmark)

    El-Ali, Henrik H; Eckerwall, Martin; Skovgaard, Dorthe

    2012-01-01

    : Small animal image-based measurements of the activity amount and the volumes of the spheres with a priori known volumes showed a good agreement with their corresponding actual volumes. The CT scans of the rats showed thyroid volumes from 34-70 mL. CONCLUSIONS: The wide span in volumes of thyroid glands......OBJECTIVE: A thyroid rat model combining functional and anatomical information would be of great benefit for better modeling of thyroid physiology and for absorbed dose calculations. Our aim was to show that (124)I-PET and CT small animal imaging are useful as a combined model for studying thyroid...... physiology and dose calculation. METHODS: Seven rats were subjects for multiple thyroid (124)I-imaging and CT-scans. S-values [mGy/MBqs] for different thyroid sizes were simulated. A phantom with spheres was designed for validation of performances of the small animal PET and CT imaging systems. RESULTS...

  14. Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance

    OpenAIRE

    Manzano, Manuel; Giron, Mar?a D; Vilchez, Jos? D.; Sevillano, Natalia; El-Azem, Nuri; Rueda, Ricardo; Salto, Rafael; Lopez-Pedrosa, Jose M.

    2016-01-01

    Background Apple polyphenols could represent a novel nutritional approach in the management and control of blood glucose, especially in type 2 diabetics. The aim of this study was to test the therapeutic potential of an apple polyphenol extract (APE) in an insulin-resistant rat model and to determine the molecular basis of insulin sensitivity action in skeletal muscle cells. Methods Acute effect of APE on the postprandial hyperglycemic response was assayed in 15?week old obese Zucker rats (OZ...

  15. Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results

    OpenAIRE

    Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger; H?rtl, Roger

    2010-01-01

    Study type: ?Basic science Introduction: ?Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful...

  16. A split luciferase complementation assay for studying in vivo protein-protein interactions in filamentous ascomycetes.

    Science.gov (United States)

    Kim, Hee-Kyoung; Cho, Eun Ji; Jo, Seong mi; Sung, Bo Reum; Lee, Seunghoon; Yun, Sung-Hwan

    2012-06-01

    Protein-protein interactions play important roles in controlling many cellular events. To date, several techniques have been developed for detection of protein-protein interactions in living cells, among which split luciferase complementation has been applied in animal and plant cells. Here, we examined whether the split luciferase assay could be used in filamentous ascomycetes, such as Gibberella zeae and Cochliobolus heterostrophus. The coding sequences of two strongly interacting proteins (the F-box protein, FBP1, and its partner SKP1) in G. zeae, under the control of the cryparin promoter from Cryphonectria parasitica, were translationally fused to the C- and N-terminal fragments of firefly luciferase (luc), respectively. Each fusion product inserted into a fungal transforming vector carrying the gene for resistance to either geneticin or hygromycin B, was transformed into both fungi. We detected complementation of split luciferase proteins driven by interaction of the two fungal proteins with a high luminescence intensity-to-background ratio only in the fungal transformants expressing both N-luc and C-luc fusion constructs. Using this system, we also confirmed a novel protein interaction between transcription factors, GzMCM1 and FST12 in G. zeae, which could hardly be proven by the yeast two-hybrid method. This is the first study demonstrating that monitoring of split luciferase complementation is a sensitive and efficient method of studying in vivo protein-protein interactions in filamentous ascomycetes.

  17. In vitro and in vivo pathogenicity studies of Pasteurella multocida strains harbouring different ompA.

    Science.gov (United States)

    Katoch, Shailja; Sharma, Mandeep; Patil, R D; Kumar, Sandeep; Verma, Subhash

    2014-09-01

    Pasteurella multocida is a pathogenic, Gram-negative bacterium that is commonly found as normal flora in nasopharynx of variety of wild and domestic animals. Numerous virulence factors have been described for P. multocida isolates which include adherence and colonization factors, iron-regulated and acquisition proteins, extracellular enzymes such as neuraminidase, lipopolysaccharide (LPS), capsule and a variety of outer membrane proteins (Omp). OmpA has a significant role in stabilizing the cell envelope structure by providing physical linkage between the outer membrane & peptidoglycan. It has been shown to mediate P. multocida -host cells interaction via heparin and/or fibronectin binding and therefore act as an important invasive molecule which could determine the final outcome of initial infection. Comparative nucleotide sequence analysis of ompA gene of P. multocida has revealed that despite extensive genetic diversity in ompA of P. multocida, most sequences could be classified into two major allele classes namely ompA allele (I) and allele (II). The P. multocida recovered from nasal cavity of bovine and belonging to two ompA classes were tested for their differential virulence. In vitro pathogenicity studies on Madin Darby Bovine Kidney (MDBK) cell line employing adhesion and invasion assays indicated that P. multocida strain with ompA (I) is more invasive than P. multocida strain with ompA (II). In vivo studies in mice further reiterated that the isolates harbouring ompA(I) were comparatively more virulent to isolates harbouring ompA (II).

  18. Multicomponent solid forms of felodipine: preparation, characterisation, physicochemical and in-vivo studies.

    Science.gov (United States)

    Chadha, Renu; Sharma, Mohit; Haneef, Jamshed

    2017-03-01

    This study aimed to improve biopharmaceutical parameters of the poorly soluble antihypertensive drug, felodipine, by preparing multicomponent solid forms using three coformers, viz. imidazole, nicotinamide and malonic acid. The multicomponent solid forms were prepared by mechanochemical synthesis and characterised by various analytical techniques. These solid forms were further assessed for their physicochemical parameters. Pharmacokinetic and in-vivo antihypertensive activity was performed in rats. Felodipine (FEL) was found to be cocrystallised with imidazole (FEL-IM) while it formed eutectic with nicotinamide (FEL-NCT) and malonic acid (FEL-MA). Cocrystal was sustained by NH…N and NH….O hydrogen-bonded network. Solubility and intrinsic dissolution studies in 0.1 N HCl (pH 1.2) revealed that eutectics exhibited higher solubility and release rate than cocrystal vis-a-vis pure drug and were found to be stable under accelerated storage condition. Significant enhancement of bioavailability was observed in eutectics (3.5- to twofold) and cocrystal (1.3-fold) compared with the pure drug. Antihypertensive activity of new solid forms in an animal model showed a marked decrease in systolic blood pressure. Mechanochemical approach was successful to prepare multicomponent solid forms that have the potential to improve biopharmaceutical parameters of the poorly soluble drug, FEL. © 2017 Royal Pharmaceutical Society.

  19. Recombinant immunotoxins with low endotoxins for clinical and animal studies.

    Science.gov (United States)

    Onda, Masanori

    2012-01-01

    Recombinant immunotoxin (RIT) contains the Fv portion of the antibody fused to the truncated form of toxin and are ongoing in clinical trials for cancer therapy. To obtain high yields of products, RITs are produced in Escherichia coli (E. coli). As the endotoxin came from E. coli cells and is harmful to animals, it is important to produce the RITs with low endotoxin. This section describes the protocols to produce RITs containing low level of endotoxins.

  20. Experimental Design and Data Analysis of In Vivo Fluorescence Imaging Studies.

    Science.gov (United States)

    Ding, Ying; Lin, Hui-Min

    2016-01-01

    The objective of this chapter is to provide researchers who conduct in vivo fluorescence imaging studies with guidance in statistical aspects in the experimental design and data analysis of such studies. In the first half of this chapter, we introduce the key statistical components for designing a sound in vivo experiment. Particular emphasis is placed on the issues and designs that pertain to fluorescence imaging studies. Examples representing several popular types of fluorescence imaging experiments are provided as case studies to demonstrate how to appropriately design such studies. In the second half of this chapter, we explain the fundamental statistical concepts and methods used in the data analysis of typical in vivo experiments. We also provide specific examples in in vivo imaging studies to illustrate the key steps of analysis procedure.

  1. Making an animal model for Korean mummy studies.

    Science.gov (United States)

    Oh, Chang Seok; Shin, Dong Hoon

    2014-01-01

    The recent findings of a series of thorough investigations into Korean mummies notwithstanding, many questions on the exact mechanism of the mummification process remain. For the purposes of a more comprehensive understanding of this mechanism, we employed an animal model involving Sprague-Dawley rats and miniature lime-soil-mixture barrier (LSMB)-surrounded Joseon tombs constructed in our lab. The results showed that long-duration burial in these LSMB tombs successfully induced animal mummification. Indeed, our gross and microscopic examinations confirmed that the rats were perfectly mummified in the manner of actual Korean mummies dating to the Joseon period. In light of the fact that the extent of mummification was not remarkable in other miniature tombs without LSMB, it seemed that the LSMB is somehow closely correlated with mummification in Korea. In the future, use of the present animal models and miniature tombs no doubt will experimentally verify the many possible factors operative in the specific mechanism of mummification in Korea.

  2. Ultrahigh resolution and brilliance laser wakefield accelerator betatron x-ray source for rapid in vivo tomographic microvasculature imaging in small animal models

    Science.gov (United States)

    Fourmaux, Sylvain; Kieffer, Jean-Claude; Krol, Andrzej

    2017-03-01

    We are developing ultrahigh spatial resolution (FWHM microvasculature imaging micro-CT angiography (μCTA) in small animal models using optimized contrast agent. It exploits Laser Wakefield Accelerator (LWFA) betatron x-ray emission phenomenon. Ultrashort high-intensity laser pulse interacting with a supersonic gas jet produces an ion cavity ("bubble") in the plasma in the wake of the laser pulse. Electrons that are injected into this bubble gain energy, perform wiggler-like oscillations and generate burst of incoherent x-rays with characteristic duration time comparable to the laser pulse duration, continuous synchrotron-like spectral distribution that might extend to hundreds keV, very high brilliance, very small focal spot and highly directional emission in the cone-beam geometry. Such LWFA betatron x-ray source created in our lab produced 1021 -1023 photonsṡ shot-1ṡmrad-2ṡmm-2/0.1%bw with mean critical energy in the12-30 keV range. X-ray source size for a single laser shot was FWHM=1.7 μm x-ray beam divergence 20-30 mrad, and effective focal spot size for multiple shots FWHM= 2 μm. Projection images of simple phantoms and complex biological objects including insects and mice were obtained in single laser shots. We conclude that ultrahigh spatial resolution μCTA (FWHM 2 μm) requiring thousands of projection images could be accomplished using LWFA betatron x-ray radiation in approximately 40 s with our existing 220 TW laser and sub seconds with next generation of ultrafast lasers and x-ray detectors, as opposed to several hours required using conventional microfocal x-ray tubes. Thus, sub second ultrahigh resolution in vivo microtomographic microvasculature imaging (in both absorption and phase contrast mode) in small animal models of cancer and vascular diseases will be feasible with LWFA betatron x-ray source.

  3. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies

    Directory of Open Access Journals (Sweden)

    Venkateswarlu Vobalaboina

    2009-02-01

    Full Text Available Abstract The aim of the study is to prepare aqueous dispersions of lipid nanoparticles – flurbiprofen solid lipid nanoparticles (FLUSLN and flurbiprofen nanostructured lipid carriers (FLUNLC by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1 and NLC gel (B1 for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 ± 2.77 μg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 ± 2.96 μg/ml. The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel

  4. ANIMAL MODELS FOR STUDYING MISCARRIAGE: ILLUSTRATION WITH STUDY OF DRINKING WATER DISINFECTION BY-PRODUCTS

    Science.gov (United States)

    Animal models for studying miscarriage: Illustration with study of drinking water disinfection by-productsAuthors & affiliations:Narotsky1, M.G. and S. Bielmeier Laffan2.1Reproductive Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Tri...

  5. Modality comparison for small animal radiotherapy: A simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Bazalova, Magdalena, E-mail: bazalova@stanford.edu; Nelson, Geoff; Noll, John M.; Graves, Edward E. [Department of Radiation Oncology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California 94305 (United States)

    2014-01-15

    Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approaches—a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by

  6. In Vivo Measurements of Tumor Metabolism and Growth after Administration of Enzastaurin Using Small Animal FDG Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Karen E. Pollok

    2009-01-01

    Full Text Available Background. The use of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG may help to establish the antitumor activity of enzastaurin, a novel protein kinase C-beta II (PKC-II inhibitor, in mouse xenografts. Methods. The hematologic cell line RAJI and the solid tumor cell line U87MG were each implanted in NOD/SCID mice. Standard tumor growth measurements and [18F]FDG PET imaging were performed weekly for up to three weeks after tumor implantation and growth. Results. Concomitant with caliper measurements, [18F]FDG PET imaging was performed to monitor glucose metabolism. Heterogeneity of glucose uptake in various areas of the tumors was observed after vehicle or enzastaurin treatment. This heterogeneity may limit the use of [18F]FDG PET imaging to measure enzastaurin-associated changes in xenograft tumors. Conclusion. [18F]FDG PET imaging technique does not correlate with standard caliper assessments in xenografts to assess the antitumor activity of enzastaurin. Future studies are needed to determine the use of [18F]FDG PET imaging in preclinical models.

  7. Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies.

    Science.gov (United States)

    Tjandrawinata, Raymond R; Trisina, Jessica; Rahayu, Puji; Prasetya, Lorentius Agung; Hanafiah, Aang; Rachmawati, Heni

    2014-01-01

    DLBS1033 is a bioactive protein fraction isolated from Lumbricus rubellus that tends to be unstable when exposed to the gastrointestinal environment. Accordingly, appropriate pharmaceutical development is needed to maximize absorption of the protein fraction in the gastrointestinal tract. In vitro, ex vivo, and in vivo stability assays were performed to study the stability of the bioactive protein fraction in gastric conditions. The bioactive protein fraction DLBS1033 was found to be unstable at low pH and in gastric fluid. The "enteric coating" formulation showed no leakage in gastric fluid-like medium and possessed a good release profile in simulated intestinal medium. DLBS1033 was absorbed through the small intestine in an intact protein form, confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) analysis. This result confirmed that an enteric coating formula using methacrylic acid copolymer could protect DLBS1033 from the acidic condition of the stomach by preventing the release of DLBS1033 in the stomach, while promoting its release when reaching the intestine. From the blood concentration-versus-time curve, (99m)Tc-DLBS1033 showed a circulation half-life of 70 minutes. This relatively long biological half-life supports its function as a thrombolytic protein. Thus, an enteric delivery system is considered the best approach for DLBS1033 as an oral thrombolytic agent.

  8. Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study.

    Science.gov (United States)

    Kataria, Hardeep; Gupta, Muskan; Lakhman, Sukhwinder; Kaur, Gurcharan

    2015-10-01

    Ashwagandha (Withania somnifera) has a long history in traditional medicines as an aphrodisiac. It has been known to influence sexual behaviour in animal models but mechanism of action is still unknown. The present study was aimed to investigate the mechanisms by which Ashwagandha extract exert its gonadotropic activities. Due to the complexity of neuroendocrine pathways, there are limited in vitro models available despite the strong demand for such systems to study and predict neuroendocrine effects of chemicals or natural products. Immortalized rat hypothalamic GnV-3 cell line was investigated as a model to screen for neuroendocrine effects of Ashwagandha extract. GnV-3 cells were cultured under different media conditions and evaluated after treatment with Ashwagandha water extract, for GnRH expression and release by immunostaining and ELISA respectively. These cells acquired differentiated morphology, characteristic shape displayed by preoptic GnRH neurons in vivo. In addition, GnV-3 cells exhibited upregulation of plasticity related polysialylated neural cell adhesion molecule (PSA-NCAM) and mature dendrite marker microtubule associated protein (MAP2) as well as GnRH expression and release. Chloroform fraction of the extract proved to exhibit all the bioactive properties as it induced differentiation and upregulated GnRH and MAP2 expression in GnV-3 cells, similar to Ashwagandha extract. Withanone and Withaferin A were found to be present in ASH-WEX and chloroform fraction while Withanone came out to be the major constituent of chloroform fraction. The preliminary in vivo studies in adult male animals showed that ASH-WEX was able to upregulate the GnRH levels although non-significantly. Taken together, this data demonstrate significant morphological and physiological changes in GnV-3 cells after treatment with Ashwagandha extract and may suggest the potential beneficial effects of Ashwagandha on reproductive functions in vivo. Copyright © 2015 Elsevier Ltd

  9. Nitrobenzene potential human cancer risk based on animal studies.

    Science.gov (United States)

    Holder, J W

    1999-08-01

    Inhaled nitrobenzene (NB) in animals produces cancer at eight sites in three rodent strains. B6C3F1 mice respond with mammary gland malignant tumors and male lung and thyroid benign tumors, and F344/N male rats respond with liver malignant tumors and thyroid and kidney benign tumors, while females respond with endometrial polyps. Male Sprague-Dawley male rats (CD strain) respond with liver benign tumors. NB is oxidized to various phenolic metabolites, while also being reduced to nitrosobenzene (NOB), phenylhydroxylamine (PH), related free radicals, and aniline (AN) in the cecum by bacteria and in the body by the microsomes. In reduction, NB first forms the nitroanion free radical, which can react with O2 to form O2*-. Repeated NB dosing produces a persistent redox couple NOBPH in red blood cells that generates met-Hb and expends NAD(P)H. NOB forms activated glutathione conjugates. These biochemical effects may lead to critical redox imbalances and macromolecular binding. Known effects are hemosiderosis, methemoglobinemia, and anemia--and now dispersed cancer in rodents. Based on structural and mechanistic similarities, NB compares with other animal and human carcinogenic nitroarenes and aromatic amines. The cancer hazard evaluation of NB is that it is a probable human carcinogen by any route of exposure. The maximum response is in F344/N male rats which is used for dose-response modelling. The model to estimate the upper 95% confidence limit (UCL95%) of NB human carcinogenicity is a no-threshold, linear low-dose, and multistaged animal model (LMS). The UCL95% of cancer slope is estimated to be 0.11(6) mg/kg/day (mkd). At de minimus risk (1:10(6)), the virtually safe dose (VSD) is estimated to be 9.1 ng/kg/day (nkd).

  10. Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ebersole, B.L.J.

    1985-01-01

    The localization of (/sup 3/H)-d-lysergic acid diethylamide ((/sup 3/H)LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with (/sup 3/H)LSD in vitro revealed substantial specific (/sup 3/H)LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received (/sup 3/H)LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies of brain areas from mice that received injections of (/sup 3/H)LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free (/sup 3/H)LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of (/sup 3/H)LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of (/sup 3/H)LSD binding in hippocampus was attributable to a lower density of sites labeled by (/sup 3/H)LSD. The pharmacological identify of (/sub 3/H)LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens.

  11. Methyglyoxal administration induces modification of hemoglobin in experimental rats: An in vivo study.

    Science.gov (United States)

    Banerjee, Sauradipta

    2017-02-01

    Methylglyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. In the present study, the effect of methylglyoxal on experimental rat hemoglobin in vivo has been investigated with respect to structural alterations and amino acid modifications, after external administration of the α-dicarbonyl compound in animals. Different techniques, mostly biophysical, were used to characterize and compare methylglyoxal-treated rat hemoglobin with that of control, untreated rat hemoglobin. In comparison with methylglyoxal-untreated, control rat hemoglobin, hemoglobin of methylglyoxal-treated rats (32mg/kgbodywt.dose) exhibited slightly decreased absorbance around 280nm, reduced intrinsic fluorescence and lower surface hydrophobicity. The secondary structures of hemoglobin of control and methylglyoxal-treated rats were more or less identical with the latter exhibiting slightly increased α-helicity compared to the former. Compared to control rat hemoglobin, methylglyoxal-treated rat hemoglobin showed higher stability. Peptide mass fingerprinting analysis revealed modifications of Arg-31α, Arg-92α and Arg-104β of methylglyoxal-treated rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to be associated with the observed structural alterations of the heme protein. Considering the increased level of methylglyoxal in diabetes mellitus as well as its high reactivity, AGE-induced modifications may have physiological significance. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. In Vitro and In Vivo Infectious Potential of Coxiella burnetii: A Study on Belgian Livestock Isolates

    Science.gov (United States)

    Mori, Marcella; Boarbi, Samira; Michel, Patrick; Bakinahe, Raïssa; Rits, Katleen; Wattiau, Pierre; Fretin, David

    2013-01-01

    Q-fever is a zoonosis caused by the gram-negative obligate intracellular pathogen Coxiella burnetii. Since its discovery, and particularly following the recent outbreaks in the Netherlands, C. burnetii appeared as a clear public health concern. In the present study, the infectious potential displayed by goat and cattle isolates of C. burnetii was compared to a reference strain (Nine Mile) using both in vitro (human HeLa and bovine macrophage cells) and in vivo (BALB/c mice) models. The isolates had distant genomic profiles with one - the goat isolate - being identical to the predominant strain circulating in the Netherlands during the 2007–2010 outbreaks. Infective doses were established with ethidium monoazide-PCR for the first time here applied to C. burnetii. This method allowed for the preparation of reproducible and characterized inocula thanks to its capacity to discriminate between live and dead cells. Globally, the proliferative capacity of the Nine Mile strain in cell lines and mice was higher compared to the newly isolated field strains. In vitro, the bovine C. burnetii isolate multiplied faster in a bovine macrophage cell line, an observation tentatively explained by the preferential specificity of this strain for allogeneic host cells. In the BALB/c mouse model, however, the goat and bovine isolates multiplied at about the same rate indicating no peculiar hypervirulent behavior in this animal model. PMID:23840751

  13. NMR studies of renal phosphate metabolites in vivo: Effects of hydration and dehydration

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, S.D.; Eng, C.; Balaban, R.S. (National Institutes of Health, Bethesda, MD (USA))

    1988-10-01

    The present study characterizes the {sup 31}P-nuclear magnetic resonance (NMR) spectrum of rabbit kidneys in vivo and evaluates the effect of hydration on phosphorous metabolites including the organic solute glycerophosphorylcholine (GPC). Cortical phosphorylethanolamine is the predominant component of the phosphomonoester region of the {sup 31}P spectrum. The contribution of blood to the spectrum is mainly from 2,3 diphosphoglycerate, which comprises {approximately}30% of the inorganic phosphate region. Acute infusion of 0.9% saline decreases the sodium content of the inner medulla by >50% in 15 min as shown by {sup 23}Na imaging. Despite this medullary Na dilution, no change in renal GPC content was observed for >1 h even with the addition of furosemide or furosemide and antidiuretic hormone. However, 20 h of chronic dehydration with 0.45% saline did result in a 30% decrease in renal GPC content when compared with dehydrated animals. These findings are consistent with GPC not playing a role in the short-term regulation of the medullary intracellular milieu in response to acute reductions in medullary Na content.

  14. The effect of squalene on inflammation factors induced by candida albicans in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Haeng [Dept. of Radiology, Nambu University, Gwangju (Korea, Republic of)

    2016-09-15

    In the present study, whether squalene treatment relives inflammatory reactions induced by Candida albicans was checked. The experiment was conducted in vivo using seven experimental animals (ICR mice) per experimental group. Among C. albicans-induced inflammatory factors, TNF-α, IL-6, and NO were observed using the ELISA kits method. Through the experiment, the following conclusions were obtained. 1. In the group infected with C. albicans, it could be identified that squalene treatment was inducing NO generation in renal tissues both on the 1st and 3rd days (p < 0.05). 2. In the group pre-treated(intraperitoneal administration) with SQ (80ml/kg) once per day for seven days and infected with C. albicans, it could be identified that squalene treatment was inducing TNF-α generation in renal tissues only on the 3rd day(p < 0.05). 3. In the group pre-treated(intraperitoneal administration) with SQ (80ml/kg) once per day for seven days and infected with C. albicans, it could be identified that squalene treatment was inducing IL-6 generation in renal tissues only on the 3rd day(p < 0.05). In conclusion, it could be seen that for squalene to suppress C. albicans-induced inflammatory factors, preemptively supplying SQ should be effective. Therefore, effects for recovery from C. albicans-induced immunodepression can be expected from SQ treatment.

  15. Image-Guided High Intensity Focused Ultrasound System for Large Animal Nerve Ablation Studies.

    Science.gov (United States)

    Worthington, Arthur; Peng, Philip; Rod, Kevin; Bril, Vera; Tavakkoli, Jahan

    2016-01-01

    High intensity focused ultrasound (HIFU) is a form of thermal ablation technique, which can treat a variety of medical afflictions. One promising therapeutic use is the permanent destruction of nerves non-invasively in patients with severe spasticity or certain types of pain (e.g., phantom limb pain). To this end, HIFU requires ultrasound guidance, which allows the non-invasive, target-specific deposition of thermal energy to the targeted nerve, thereby blocking axonal conduction. In this paper, a composite system comprising both ultrasound-imaging and HIFU therapy was developed and used to induce localized non-invasive nerve blockage in an in vivo large animal study. Five pigs were used with the femoral nerve as the target. Calibrated needle thermocouples inserted at the target site were employed to monitor the target tissue temperature. The degree of nerve blockage was assessed by measuring compound action potential (CAP) signal with a clinical nerve electrophysiology system before and after HIFU exposures. An average CAP signal amplitude reduction of 49% of baseline with a standard deviation of 9% was observed after 20-30 min post exposure. These results demonstrate the feasibility of the proposed ultrasound-guided HIFU modality as a potential non-invasive nerve ablation method.

  16. International symposium on in vivo body composition studies: Program and abstracts

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    This booklet contains the program and individual abstracts for papers presented at the International symposium on in vivo body composition studies. The presentations were divided into five sessions. Individual abstracts were indexed for the Energy Data Base. (DT)

  17. Insights from the Study of Animals Lacking Functional Estrogen Receptor

    Science.gov (United States)

    Korach, Kenneth S.

    1994-12-01

    Estrogen hormones produce physiological actions within a variety of target sites in the body and during development by activating a specific receptor protein. Hormone responsiveness for the estrogen receptor protein was investigated at different stages of development with the use of gene knockout techniques because no natural genetic mutants have been described. A mutant mouse line without a functional estrogen receptor was created and is being used to assess estrogen responsiveness. Both sexes of these mutant animals are infertile and show a variety of phenotypic changes, some of which are associated with the gonads, mammary glands, reproductive tracts, and skeletal tissues.

  18. Pilot in vivo animal study of bone regeneration by fractional Er: YAG-laser

    Science.gov (United States)

    Altshuler, Gregory B.; Belikov, Andrey V.; Shatilova, Ksenia V.; Yaremenko, Andrey I.; Zernitskiy, Alexander Y.; Zernitckaia, Ekaterina A.

    2016-04-01

    The histological structure of the rabbit parietal bone during its regeneration after fractional Er: YAG-laser (λ=2.94μm) treatment was investigated by hematoxylin and eosin (H&E) stain. In 48 days after fractional laser treatment, bone samples contained micro-cavities and fragments of necrotic tissue with empty cellular lacuna and coagulated protein of bone matrix. In this case, necrotic lesions appeared around the periphery of micro-cavities created by laser radiation. Fragmentation of detrital mass and partial substitution of micro-cavities with fatty bone marrow were observed in bone samples in 100 days after fractional laser treatment, in contrast to the earlier period. Partial filling of micro-cavities edges by fibrous tissue with presence of osteoblasts on their inner surface was observed in 100 days also, that indicates regenerative processes in the bone.

  19. Animal and model systems for studying cystic fibrosis.

    Science.gov (United States)

    Rosen, Bradley H; Chanson, Marc; Gawenis, Lara R; Liu, Jinghua; Sofoluwe, Aderonke; Zoso, Alice; Engelhardt, John F

    2017-09-19

    The cystic fibrosis (CF) field is the beneficiary of five species of animal models that lack functional cystic fibrosis transmembrane conductance regulator (CFTR) channel. These models are rapidly informing mechanisms of disease pathogenesis and CFTR function regardless of how faithfully a given organ reproduces the human CF phenotype. New approaches of genetic engineering with RNA-guided nucleases are rapidly expanding both the potential types of models available and the approaches to correct the CFTR defect. The application of new CRISPR/Cas9 genome editing techniques are similarly increasing capabilities for in vitro modeling of CFTR functions in cell lines and primary cells using air-liquid interface cultures and organoids. Gene editing of CFTR mutations in somatic stem cells and induced pluripotent stem cells is also transforming gene therapy approaches for CF. This short review evaluates several areas that are key to building animal and cell systems capable of modeling CF disease and testing potential treatments. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Evaluation of bioaccumulation using in vivo laboratory and field studies.

    Science.gov (United States)

    Weisbrod, Annie V; Woodburn, Kent B; Koelmans, Albert A; Parkerton, Thomas F; McElroy, Anne E; Borgå, Katrine

    2009-10-01

    A primary consideration in the evaluation of chemicals is the potential for substances to be absorbed and retained in an organism's tissues (i.e., bioaccumulated) at concentrations sufficient to pose health concerns. Substances that exhibit properties that enable biomagnification in the food chain (i.e., amplification of tissue concentrations at successive trophic levels) are of particular concern due to the elevated long-term exposures these substances pose to higher trophic organisms, including humans. Historically, biomarkers of in vivo chemical exposure (e.g., eggshell thinning, bill deformities) retrospectively led to the identification of such compounds, which were later categorized as persistent organic pollutants. Today, multiple bioaccumulation metrics are available to quantitatively assess the bioaccumulation potential of new and existing chemicals and identify substances that, upon or before environmental release, may be characterized as persistent organic pollutants. This paper reviews the various in vivo measurement approaches that can be used to assess the bioaccumulation of chemicals in aquatic or terrestrial species using laboratory-exposed, field-deployed, or collected organisms. Important issues associated with laboratory measurements of bioaccumulation include appropriate test species selection, test chemical dosing methods, exposure duration, and chemical and statistical analyses. Measuring bioaccumulation at a particular field site requires consideration of which test species to use and whether to examine natural populations or to use field-deployed populations. Both laboratory and field methods also require reliable determination of chemical concentrations in exposure media of interest (i.e., water, sediment, food or prey, etc.), accumulated body residues, or both. The advantages and disadvantages of various laboratory and field bioaccumulation metrics for assessing biomagnification potential in aquatic or terrestrial food chains are discussed

  1. Animal models for vaccine studies for visceral leishmaniasis.

    Science.gov (United States)

    Garg, Ravendra; Dube, Anuradha

    2006-03-01

    Visceral leishmaniases (VL) or kala-azar is the most dreaded and devastating amongst the various forms of leishmaniases. The disease, though localized in certain areas only, has gained immense importance because of high mortality rate, mainly in children. The parasite is responsible for a spectrum of clinical syndromes, which can, in most extreme cases, go from an asymptomatic infection to a fatal form of VL. Chemotherapeutic measures, alone are not sufficient to control and contain the disease. As an alternate strategy, vaccination is also under experimental and clinical trails. The situation unquestionably demands the use of proper screening system, rationale chemical synthesis, vaccine development and targeted vaccine delivery. Thus, development of an acceptable vaccine is not an easy task. While the factors, which determine clinical outcomes, are in part, a feature of the parasite, it is the nature of the host and its genetic make up and immune status that play crucial role. The prerequisite of reliable animal model is that it should have a considerably good correlation with the clinical situation and is expected to mimic the pathological features and immunological responses observed in humans when exposed to a variety of Leishmania spp. with different pathogenic characteristics. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. In addition to the nature of the host, the major difference between natural and experimental infections is the parasite inoculum; in natural conditions, the infected sand fly vector deposits a few hundred metacyclic promastigotes into the dermis of the host, whereas experimental infections are induced by the injection (subcutaneous or intravenous) of millions of promastigotes grown in axenic cultures in vitro or amastigotes recovered from infected spleens. In public health terms, VL is the disease of humans and dogs

  2. Animal models of pancreatitis: Can it be translated to human pain study?

    Science.gov (United States)

    Zhao, Jing-Bo; Liao, Dong-Hua; Nissen, Thomas Dahl

    2013-01-01

    Chronic pancreatitis affects many individuals around the world, and the study of the underlying mechanisms leading to better treatment possibilities are important tasks. Therefore, animal models are needed to illustrate the basic study of pancreatitis. Recently, animal models of acute and chronic pancreatitis have been thoroughly reviewed, but few reviews address the important aspect on the translation of animal studies to human studies. It is well known that pancreatitis is associated with epigastric pain, but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear. Using animal models to study pancreatitis associated visceral pain is difficult, however, these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain. In this review, the animal models of acute, chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed. PMID:24259952

  3. The potential of isotopically enriched magnesium to study bone implant degradation in vivo.

    Science.gov (United States)

    Draxler, Johannes; Martinelli, Elisabeth; Weinberg, Annelie M; Zitek, Andreas; Irrgeher, Johanna; Meischel, Martin; Stanzl-Tschegg, Stefanie E; Mingler, Bernhard; Prohaska, Thomas

    2017-03-15

    This pilot study highlights the substantial potential of using isotopically enriched (non-radioactive) metals to study the fate of biodegradable metal implants. It was possible to show that magnesium (Mg) release can be observed by combining isotopic mass spectrometry and isotopic pattern deconvolution for data reduction, even at low amounts of Mg released a from slowly degrading (26)Mg enriched (>99%) Mg metal. Following implantation into rats, structural in vivo changes were monitored by μCT. Results showed that the applied Mg had an average degradation rate of 16±5μmyear(-1), which corresponds with the degradation rate of pure Mg. Bone and tissue extraction was performed 4, 24, and 52weeks after implantation. Bone cross sections were analyzed by laser ablation inductively coupled plasma mass spectrometry (ICP-MS) to determine the lateral (26)Mg distribution. The (26)Mg/(24)Mg ratios in digested tissue and excretion samples were analyzed by multi collector ICP-MS. Isotope pattern deconvolution in combination with ICP-MS enabled detection of Mg pin material in amounts as low as 200ppm in bone tissues and 20ppm in tissues up to two fold increased Mg levels with a contribution of pin-derived Mg of up to 75% (4weeks) and 30% (24weeks) were found adjacent to the implant. After complete degradation, no visual bone disturbance or residual pin-Mg could be detected in cortical bone. In organs, increased Δ(26)Mg/(24)Mg values up to 16‰ were determined compared to control samples. Increased Δ(26)Mg/(24)Mg values were detected in serum samples at a constant total Mg level. In contrast to urine, feces did not show a shift in the (26)Mg/(24)Mg ratios. This investigation showed that the organism is capable of handling excess Mg well and that bones fully recover after degradation. Magnesium alloys as bone implants have faced increasing attention over the past years. In vivo degradation and metabolism studies of these implant materials have shown the promising application

  4. Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin

    Energy Technology Data Exchange (ETDEWEB)

    Cenedella, R.J.; Fleschner, C.R. (Kirksville College of Osteopathic Medicine, MO (USA))

    1990-10-01

    The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea.

  5. Stratum corneum damage and ex vivo porcine skin water absorption - a pilot study

    DEFF Research Database (Denmark)

    Duch Lynggaard, C; Bang Knudsen, D; Jemec, G B E

    2009-01-01

    A simple ex vivo screening technique would be of interest for mass screening of substances for potential barrier disruptive qualities. Ex vivo water absorption as a marker of skin barrier integrity was studied on pig ear skin. Skin water absorption was quantified by weighing and weight changes were...... found to reflect prehydration barrier damage. It is suggested that this simple model may be elaborated to provide a rapid, economical screening tool for potential skin irritants....

  6. In vivo studies with a dicalcium phosphate dihydrate/MFP system for caries prevention.

    Science.gov (United States)

    Gaffar, A; Blake-Haskins, J; Mellberg, J

    1993-02-01

    Recent basic studies have shown that increasing supersaturation with respect to dicalcium phosphate dihydrate (DCPD), above and beyond the amount present in saliva, enhanced the efficacy of fluoride in vitro. Since the combination of monofluorophosphate (MFP) with DCPD abrasive is unique for fluoride stability, dentifrices containing the combination were evaluated in a variety of in vivo tests. MFP with silicon dioxide (silica) abrasive at an equivalent fluoride concentration was used for comparison. The influence of slurries of DCPD or silicon dioxide on the intraoral plaque pH was measured following sucrose challenge in humans. The data indicated that DCPD slurries were more effective than silica in preventing plaque pH drop when compared to silica. A toothpaste containing MFP and DCPD was significantly more effective than an MFP/silica toothpaste. A toothpaste containing radiolabeled DCPD was applied topically in rats' teeth during a cariogenic challenge. The results showed that calcium45 was incorporated into the enamel with a concomitant reduction in enamel solubility. In a rat caries study using MFP/DCPD, matching placebo and MFP/silica, MFP/DCPD dentifrice showed a significantly greater reduction in smooth surface caries. Two dentifrices were also tested in an in situ human model for fluoride uptake in artificial root caries lesions where MFP/DCPD provided a significantly higher fluoride uptake than MFP/silica. A second in situ study in humans evaluated the same dentifrices. MFP/DCPD increased salivary plaque calcium and fluoride. These results of laboratory, animal and in situ studies taken together indicate that the MFP/DCPD combination is unique in providing extra supersaturation in saliva and plaque with concomitant enhanced anticaries efficacy.

  7. An in vivo culture system for human embryos using an encapsulation technology: a pilot study

    Science.gov (United States)

    Blockeel, C.; Mock, P.; Verheyen, G.; Bouche, N.; Le Goff, Ph.; Heyman, Y.; Wrenzycki, C.; Höffmann, K.; Niemann, H.; Haentjens, P.; de Los Santos, M.J.; Fernandez-Sanchez, M.; Velasco, M.; Aebischer, P.; Devroey, P.; Simón, C.

    2009-01-01

    BACKGROUND Animal studies have demonstrated better embryo development in vivo than in vitro. This pilot study tested the feasibility of using a novel in utero culture system (IUCS) to obtain normal human fertilization and embryo development. METHODS The IUCS device comprised a perforated silicone hollow tube. The study included 13 patients (<36 years) undergoing a first intracytoplasmic sperm injection (ICSI) treatment and 167 metaphase II oocytes in three groups. In Group 1, 1–2 h after ICSI, sibling oocytes were assigned to IUCS or conventional in vitro culture. The device was retrieved on Day 1, and all zygotes were cultured in vitro till Day 5. In Group 2, fertilized oocytes were assigned on Day 1, embryos retrieved on Day 3 and all embryos cultured till Day 5. In Group 3, after Day 0 assignment, embryos were retrieved on Day 3 for blastomere biopsy and fluorescence in situ hybridization (FISH) and cultured until Day 5. The highest quality blastocysts were transferred on Day 5. RESULTS Fertilization and embryo development were comparable in the in vitro and IUCS arms, with a tendency towards better embryo quality in the IUCS. FISH analysis in Group 3 revealed more normal embryos using the IUCS (P = 0.049). Three clinical pregnancies and live births were obtained: two from the IUCS arm and one from the in vitro arm. CONCLUSIONS Our pilot study shows that this new IUCS appears to be feasible and safe, supporting normal fertilization, embryo development and normal chromosomal segregation. Furthermore, live births are possible after the transient presence of a silicone device in the uterus.Clinicaltrials.gov: NCT00480103. PMID:19273881

  8. Bridging human and animal research: a comparative approach to studies of personality and health.

    Science.gov (United States)

    Mehta, Pranjal H; Gosling, Samuel D

    2008-07-01

    This article evaluates a comparative approach to personality and health research. We (1) review evidence showing that personality exists and can be measured in animals, (2) illustrate the benefits of animal studies for human personality research, (3) illustrate the benefits of human studies for animal personality research, and (4) provide guidelines for making cross-species comparisons. We conclude that a comparative approach can provide unique insights into personality psychology, especially into research on personality, immunity, and health.

  9. Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2014-09-01

    Full Text Available Raymond R Tjandrawinata,1 Jessica Trisina,1 Puji Rahayu,1 Lorentius Agung Prasetya,1 Aang Hanafiah,2 Heni Rachmawati3 1Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, Indonesia; 2National Nuclear Energy Agency, Bandung, Indonesia; 3School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia Abstract: DLBS1033 is a bioactive protein fraction isolated from Lumbricus rubellus that tends to be unstable when exposed to the gastrointestinal environment. Accordingly, appropriate pharmaceutical development is needed to maximize absorption of the protein fraction in the gastrointestinal tract. In vitro, ex vivo, and in vivo stability assays were performed to study the stability of the bioactive protein fraction in gastric conditions. The bioactive protein fraction DLBS1033 was found to be unstable at low pH and in gastric fluid. The “enteric coating” formulation showed no leakage in gastric fluid–like medium and possessed a good release profile in simulated intestinal medium. DLBS1033 was absorbed through the small intestine in an intact protein form, confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE analysis. This result confirmed that an enteric coating formula using methacrylic acid copolymer could protect DLBS1033 from the acidic condition of the stomach by preventing the release of DLBS1033 in the stomach, while promoting its release when reaching the intestine. From the blood concentration–versus-time curve, 99mTc-DLBS1033 showed a circulation half-life of 70 minutes. This relatively long biological half-life supports its function as a thrombolytic protein. Thus, an enteric delivery system is considered the best approach for DLBS1033 as an oral thrombolytic agent. Keywords: bioactive protein fraction, enteric coated tablet, pharmacodynamic

  10. In vitro and in vivo study of commercial calcium phosphate cement HydroSet™.

    Science.gov (United States)

    Kent, Niall W; Blunn, Gordon; Karpukhina, Natalia; Davis, Graham; de Godoy, Roberta Ferro; Wilson, Rory M; Coathup, Melanie; Onwordi, Lyris; Quak, Wen Yu; Hill, Robert

    2018-01-01

    The commercial calcium phosphate cement, HydroSet™, was investigated in vitro, studying phase formation, compressive strength and setting time, followed by an ovine in vivo study to measure osseointegration, bone apposition and bone-to-graft contact. The X-ray diffraction and 31 P Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) results showed the initial formation of octacalcium phosphate and hydroxyapatite at one hour. Over 7 days the octacalcium phosphate transformed to apatite, which was the only crystalline phase of the cement at 28 days. This apatite phase is thought to be a calcium deficient apatite. In the scanning electron microscopy, histological images of 12-week ovine in vivo results showed a high degree of osseointegration, 92.5%. Compressive strength comparisons between in vitro and in vivo measurements showed a dramatic difference between the in vitro measurements (highest 25.4 MPa) and in vivo (95 MPa), attributed to bone ingrowth into the cement in vivo. To the best of our knowledge this is the first time phase evolution of HydroSet™ and the properties studied in vitro complement the in vivo evaluation of the cement in a publication. The significance of the new finding of initial formation of octacalcium phosphate in this cement is discussed. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 21-30, 2018. © 2016 Wiley Periodicals, Inc.

  11. Mitochondrial DNA damage and animal longevity: insights from comparative studies.

    Science.gov (United States)

    Pamplona, Reinald

    2011-03-02

    Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS) and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA). ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

  12. Reproducibility and Variation of Diffusion Measures in the Squirrel Monkey Brain, In Vivo and Ex Vivo

    Science.gov (United States)

    Schilling, Kurt; Gao, Yurui; Stepniewska, Iwona; Choe, Ann S; Landman, Bennett A; Anderson, Adam W

    2016-01-01

    Purpose Animal models are needed to better understand the relationship between diffusion MRI (dMRI) and the underlying tissue microstructure. One promising model for validation studies is the common squirrel monkey, Saimiri sciureus. This study aims to determine (1) the reproducibility of in vivo diffusion measures both within and between subjects; (2) the agreement between in vivo and ex vivo data acquired from the same specimen and (3) normal diffusion values and their variation across brain regions. Methods Data were acquired from three healthy squirrel monkeys, each imaged twice in vivo and once ex vivo. Reproducibility of fractional anisotropy (FA), mean diffusivity (MD), and principal eigenvector (PEV) was assessed, and normal values were determined both in vivo and ex vivo. Results The calculated coefficients of variation (CVs) for both intra-subject and inter-subject MD were below 10% (low variability) while FA had a wider range of CVs, 2–14% intra-subject (moderate variability), and 3–31% inter-subject (high variability). MD in ex vivo tissue was lower than in vivo (30%–50% decrease), while FA values increased in all regions (30–39% increase). The mode of angular differences between in vivo and ex vivo PEVs was 12 degrees. Conclusion This study characterizes the diffusion properties of the squirrel monkey brain and serves as the groundwork for using the squirrel monkey, both in vivo and ex vivo, as a model for diffusion MRI studies. PMID:27587226

  13. Migration of alloplastic bone graft material in infected conditions: a case study and animal experiment.

    Science.gov (United States)

    Seok, Hyun; Lee, Seuk-Keun; Kim, Seong-Gon; Kang, Tae-Yeon; Lee, Myung-Jin; Chae, Weon-Sik

    2014-06-01

    Distant migration associated with sinus lifting procedures has not been investigated. In the present study, a case of distant migration of graft material was observed, and the potential mechanisms of migration were analyzed using material analysis and in vivo experiments. The migrated graft material was biphasic calcium phosphate-based alloplastic material (BCP), and its physical properties were compared with those of xenogenic material (Bio-Oss). The comparisons of the physical properties were performed using scanning electronic microscopic, x-ray diffraction, and Fourier-transform infrared absorbance spectra analysis. The comparative graft migration study was performed using the subcutaneous pocket model in rats (n = 10). The clinical case was analyzed by histologic section and energy dispersive x-ray (EDX) microanalysis. The observed diffraction patterns from the Bio-Oss revealed characteristic diffractions for the hydroxyapatite phase, and those from the BCP revealed additional diffractions that could be assigned to the tricalcium phosphate phase. In the animal model, the graft migration distances observed in the BCP group were significantly greater than those observed in the Bio-Oss group (P = .012). In the clinical case, the lymphatic vessels of the submandibular gland contained foreign materials that were morphologically similar to those of the maxillary sinus. EDX microanalysis revealed that the particles in the lymphatic vessels exhibited calcium concentrations that were approximately 200 times greater than those in the adjacent glandular tissue. In the present study, BCP-based sinus grafts had migrated into the submandibular glandular area by way of the lymphatic chain in the presented clinical case. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Standards for data acquisition and software-based analysis of in vivo electroencephalography recordings from animals. A TASK1-WG5 report of the AES/ILAE Translational Task Force of the ILAE.

    Science.gov (United States)

    Moyer, Jason T; Gnatkovsky, Vadym; Ono, Tomonori; Otáhal, Jakub; Wagenaar, Joost; Stacey, William C; Noebels, Jeffrey; Ikeda, Akio; Staley, Kevin; de Curtis, Marco; Litt, Brian; Galanopoulou, Aristea S

    2017-11-01

    Electroencephalography (EEG)-the direct recording of the electrical activity of populations of neurons-is a tremendously important tool for diagnosing, treating, and researching epilepsy. Although standard procedures for recording and analyzing human EEG exist and are broadly accepted, there are no such standards for research in animal models of seizures and epilepsy-recording montages, acquisition systems, and processing algorithms may differ substantially among investigators and laboratories. The lack of standard procedures for acquiring and analyzing EEG from animal models of epilepsy hinders the interpretation of experimental results and reduces the ability of the scientific community to efficiently translate new experimental findings into clinical practice. Accordingly, the intention of this report is twofold: (1) to review current techniques for the collection and software-based analysis of neural field recordings in animal models of epilepsy, and (2) to offer pertinent standards and reporting guidelines for this research. Specifically, we review current techniques for signal acquisition, signal conditioning, signal processing, data storage, and data sharing, and include applicable recommendations to standardize collection and reporting. We close with a discussion of challenges and future opportunities, and include a supplemental report of currently available acquisition systems and analysis tools. This work represents a collaboration on behalf of the American Epilepsy Society/International League Against Epilepsy (AES/ILAE) Translational Task Force (TASK1-Workgroup 5), and is part of a larger effort to harmonize video-EEG interpretation and analysis methods across studies using in vivo and in vitro seizure and epilepsy models. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. THE STUDY OF THE INFLUENCE OF MODEL MEAT SYSTEMS ON THE ALLERGIC IMMUNE RESPONSE IN VIVO

    Directory of Open Access Journals (Sweden)

    A. S. Dydykin

    2017-01-01

    Full Text Available This article presents the results of studying the effect of homogeneous model meat systems produced using enzyme preparation containing fungal protease and microbiological starter culture of Lactobacillus plantarum on the allergic reactions within specific immunity in vivo. According to the results, it is established that experimental products have no negative effect on the clinical parameters of laboratory animals. During the experiment, with the introduction of experimental products into diet, the dynamics of body weight changes in all groups of animals was positive. At the end of the experiment, there were smaller increase in the weight of rats and lower values of weight gain (Group 1 — 14.0 %, Group 2 — 15.9 %, Group 3 — 20.2 %. This is possibly due to the adaptation processes occurring in response to introduction of meat systems into the diet, which confirms the leveling of the daily weight gain of experimental and intact animals since the 16th day of the experiment. According to the results of clinical blood analysis of the animals consuming experimental products, an increase is detected in leukocytes and lymphocytes by up to 18 %; in granulocytes by up to 35 %; and in monocytes by up to 8 %; in hemoglobin concentration, hematocrit and mean corpuscular hemoglobin concentration by more than 3 %; in red cell distribution width and mean corpuscular volume by up to 2 %, in comparison with intact animals. The correlation of these data with ELISA parameters for serum of experimental animals (histamine and immunoglobulin E allowed to suggest the expression of reaginic antibodies and interaction on the surface of basophils and mast cells, which led to the degranulation and release (increase of histamine, as a vasoactive factor, by 40 % compared with intact animals.The overall conclusion of the studies is that experimental model meat systems may trigger the activation of specific immune responses in laboratory animals. This is

  16. [Comparative animal experiments of different tissue adhesives. I. Tensile strength studies. II. Histologic and morphometric studies].

    Science.gov (United States)

    Stephan, E; Buntrock, P; Köhler, S

    1989-01-01

    This paper for the first time presents the results of extensive histological and histomorphometric studies investigating the tensile strength of tissue adhesives in model experiments on animals. The material used in comparative studies were TISSEEL, a human adhesive based on fibrinogen, HISTOACRYL-blue, a cyanoacrylate, and KL-3, a type of urethane adhesive. All the materials used in these studies were shown to be principally suitable as tissue adhesives. TISSEEL, the biological adhesive, was obviously superior to all the other adhesives whereas the two synthetic adhesives HISTOACRYL-blue and KL-3 were found to be roughly equal in their properties. The animal model described in the present paper is recommended for use as a standard technique for testing the suitability of new tissue adhesives.

  17. EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

    Science.gov (United States)

    Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

  18. HPMA copolymer conjugate with pirarubicin: In vitro and ex vivo stability and drug release study.

    Science.gov (United States)

    Islam, Waliul; Fang, Jun; Etrych, Tomas; Chytil, Petr; Ulbrich, Karel; Sakoguchi, Akihiro; Kusakabe, Katsuki; Maeda, Hiroshi

    2017-11-10

    We have developed a tumor environment-responsive polymeric anticancer prodrug containing pirarubicin (THP) conjugated to N-(2-hydroxypropyl) methacrylamide copolymer (PHPMA), [P-THP], through a spacer containing pH-sensitive hydrazone bond, that showed remarkable therapeutic effect against various tumor models and in a human pilot study. Toward clinical development, here we report THP release profile from its HPMA copolymer conjugate, the conjugate stability, protein and cell-binding and solubility of P-THP. Size exclusion chromatography of P-THP (molecular weight 38 kDa) showed similar hydrodynamic volume as bovine serum albumin (BSA) in aqueous solution, with no apparent interactions with BSA, nor aggregation by itself. pH-responsive release of free THP was reconfirmed at pHs 6.5 and lower. The drug release was significantly affected by a type of used buffer. Phosphate buffer seems to facilitate faster hydrazone bond cleavage at pH 7.4 whereas higher stability was achieved in L-arginine solution which yielded only little cleavage and THP release, approx. 15% within 2 weeks at the same pH at 25 °C. Furthermore, ex vivo study using sera of different animal species showed very high stability of P-THP. Incubation with blood showed high stability of P-THP during circulation, without binding to blood cells. These findings revealed that L-arginine solution provides appropriate media for formulation of P-THP infusion solution as tumor-targeted polymeric anticancer drug based on EPR effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase: ex vivo and in vivo studies.

    Science.gov (United States)

    Jayakumar, Thanasekaran; Chen, Wei-Fan; Lu, Wan-Jung; Chou, Duen-Suey; Hsiao, George; Hsu, Chung-Yi; Sheu, Joen-Rong; Hsieh, Cheng-Ying

    2013-06-01

    Sulforaphane is a naturally occurring isothiocyanate, which can be found in cruciferous vegetables such as broccoli and cabbage. Sulforaphane was found to have very potent inhibitory effects on tumor growth through regulation of diverse mechanisms. However, no data are available concerning the effects of sulforaphane on platelet activation and its relative issues. Activation of platelets caused by arterial thrombosis is relevant to a variety of cardiovascular diseases. Hence, the aim of this study was to examine the in vivo antithrombotic effects of sulforaphane and its possible mechanisms in platelet activation. Sulforaphane (0.125 and 0.25 mg/kg) was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice. Other in vivo studies also revealed that sulforaphane (0.25 mg/kg) significantly prolonged platelet plug formation in mice. In addition, sulforaphane (15-75 μM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen. Sulforaphane inhibited platelet activation accompanied by inhibiting relative Ca(2+) mobilization; phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs) and Akt; and hydroxyl radical (OH(●)) formation. Sulforaphane markedly increased cyclic (c)AMP, but not cyclic (c)GMP levels, and stimulated vasodilator-stimulated phosphoprotein (VASP) phosphorylation. SQ22536, an inhibitor of adenylate cyclase, but not ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxal in-1-one), an inhibitor of guanylate cyclase, obviously reversed the sulforaphane-mediated effects on platelet aggregation; PKC activation, p38 MAPK, Akt and VASP phosphorylation; and OH(●) formation. Furthermore, a PI3-kinase inhibitor (LY294002) and a p38 MAPK inhibitor (SB203580) both significantly diminished PKC activation and p38 MAPK and Akt phosphorylation; in contrast, a PKC inhibitor (RO318220) did not diminish p38 MAPK or Akt phosphorylation stimulated by collagen. This

  20. Apoptosis imaging studies in various animal models using radio-iodinated peptide.

    Science.gov (United States)

    Kwak, Wonjung; Ha, Yeong Su; Soni, Nisarg; Lee, Woonghee; Park, Se-Il; Ahn, Heesu; An, Gwang Il; Kim, In-San; Lee, Byung-Heon; Yoo, Jeongsoo

    2015-01-01

    Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging. In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with (124)I and (131)I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proliferation were assessed by [(18)F]FDG and [(18)F]FLT PET imaging and compared with ApoPep-1 after doxorubicin treatment. The peptide was radiolabeled at high purity, and it showed reasonably good stability in serum. Cell death was easily imaged by radiolabeled ApoPep-1 in an ischemia surgery model. And, liver apoptosis was more clearly identified by ApoPep-1 rather than [(124)I]annexin V in cycloheximide-treated models. Three doxorubicin doses inhibited tumor growth, which was evaluated by 30-40% decreases of [(18)F]FDG and [(18)F]FLT PET uptake in the tumor area. However, ApoPep-1 demonstrated more than 200% increase in tumor uptake after chemotherapy, while annexin V did not show any meaningful uptake in the tumor compared with the background. Biodistribution data were also in good agreement with the microPET imaging results. All of the experimental data clearly demonstrated high potential of the radiolabeled ApoPep-1 for in vivo apoptosis imaging.

  1. Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

    Directory of Open Access Journals (Sweden)

    Li Cui

    2014-06-01

    Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

  2. Animal-assisted therapy used for anxiety disorders in patients with learning disabilities: An observational study

    OpenAIRE

    Giuliani, F; Jacquemettaz, M.

    2017-01-01

    Introduction: Animal-assisted therapy is defined as the positive interaction between an animal and a patient within a therapeutic framework. Previous studies have reported on the beneficial effects of animal-assisted therapy with patients suffering from anxiety, a major challenge for professionals caring for patients with intellectual disability. The presence of psychiatric comorbidities such as depression or anxiety within this population is two to four times higher than in the general popul...

  3. Laboratory studies of imitation/field studies of tradition: towards a synthesis in animal social learning.

    Science.gov (United States)

    Galef, Bennett G

    2015-03-01

    Here I discuss: (1) historical precedents that have resulted in comparative psychologists accepting the two-action method as the "gold standard" in laboratory investigations of imitation learning, (2) evidence suggesting that the two-action procedure may not be adequate to answer questions concerning the role of imitation in the development of traditional behaviors of animals living in natural habitat, and (3) an alternative approach to the laboratory study of imitation that might increase the relevance of laboratory studies of imitation to the work of behavioral ecologists/primatologists interested in animal traditions and their relationship to human cumulative culture. This article is part of a Special Issue entitled: Tribute to Tom Zentall. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies

    Science.gov (United States)

    de Vries, Rob B. M.; Wever, Kimberley E.; Avey, Marc T.; Stephens, Martin L.; Sena, Emily S.; Leenaars, Marlies

    2014-01-01

    The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic reviews. In particular, we illustrate how these reviews can help improve the methodological quality of animal experiments, make the choice of an animal model and the translation of animal data to the clinic more evidence-based, and implement the 3Rs. Moreover, we discuss which measures are being taken and which need to be taken in the future to ensure that systematic reviews will actually contribute to optimizing experimental design and thereby to meeting a necessary condition for making the use of animals in these experiments justified. PMID:25541545

  5. Breast cancer models to study the expression of estrogen receptors with small animal PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Aliaga, Antonio; Rousseau, Jacques A.; Ouellette, Rene; Cadorette, Jules; Lier, Johan E. van; Lecomte, Roger; Benard, Francois E-mail: francois.benard@USherbrooke.ca

    2004-08-01

    Different animal models of estrogen positive tumors (ER{sup +}) were evaluated for their suitability to follow tumor response after various treatment protocols, using small animal positron emission tomography (PET). ER{sup +} human breast cancer cell lines MCF-7 and T-47D, using MDA-MB-231 as ER{sup -}; control, and murine mammary ductal carcinomas MC4-L2, MC4-L3, and MC7-L1, were compared for their in vivo growth rate and retention of ER{sup +} status. Tumor metabolic activity was estimated from the relative uptake (% injected dose/g) of [{sup 18}F]fluorodeoxyglucose (FDG) uptake, whereas ER content was determined from 16{alpha}-[{sup 18}F]fluoroestradiol (FES) retention. F-18 activity values were obtained by small animal PET imaging and confirmed by tissue sampling and radioactivity counting. Reliable uptake measurements could be obtained for tumors of 200 {mu}l or over. The human cell lines grew at a slower rate in vivo and failed to accumulate FES; in contrast, the Balb/c MC7-L1 and MC4-L2 grew well and showed good uptake of both FDG and FES. Chemotherapy and hormone therapy delayed the growth of MC7-L1 and MC4-L2 tumors, confirming their suitability as an ER{sup +} model for therapeutic interventions. MC4-L3 tumors also showed promising results but required the presence of progestative pellets to grow. These data demonstrate that murine MC7-L1 and MC4-L2 tumors are suitable models for the monitoring of ER{sup +} breast cancer therapy using small animal PET imaging.

  6. Determinants associated with veterinary antimicrobial prescribing in farm animals in the Netherlands: a qualitative study.

    Science.gov (United States)

    Speksnijder, D C; Jaarsma, A D C; van der Gugten, A C; Verheij, T J M; Wagenaar, J A

    2015-04-01

    Antimicrobial use in farm animals might contribute to the development of antimicrobial resistance in humans and animals, and there is an urgent need to reduce antimicrobial use in farm animals. Veterinarians are typically responsible for prescribing and overseeing antimicrobial use in animals. A thorough understanding of veterinarians' current prescribing practices and their reasons to prescribe antimicrobials might offer leads for interventions to reduce antimicrobial use in farm animals. This paper presents the results of a qualitative study of factors that influence prescribing behaviour of farm animal veterinarians. Semi-structured interviews with eleven farm animal veterinarians were conducted, which were taped, transcribed and iteratively analysed. This preliminary analysis was further discussed and refined in an expert meeting. A final conceptual model was derived from the analysis and sent to all the respondents for validation. Many conflicting interests are identifiable when it comes to antimicrobial prescribing by farm animal veterinarians. Belief in the professional obligation to alleviate animal suffering, financial dependency on clients, risk avoidance, shortcomings in advisory skills, financial barriers for structural veterinary herd health advisory services, lack of farmers' compliance to veterinary recommendations, public health interests, personal beliefs regarding the veterinary contribution to antimicrobial resistance and major economic powers are all influential determinants in antimicrobial prescribing behaviour of farm animal veterinarians. Interventions to change prescribing behaviour of farm animal veterinarians could address attitudes and advisory skills of veterinarians, as well as provide tools to deal with (perceived) pressure from farmers and advisors to prescribe antimicrobials. Additional (policy) measures could probably support farm animal veterinarians in acting as a more independent animal health consultant. © 2014 Blackwell

  7. A comparative approach to the study of Keeper-Animal Relationships in the zoo.

    Science.gov (United States)

    Carlstead, Kathy

    2009-11-01

    Research on intensively farmed animals over the past 25 years has shown that human-animal interactions, by affecting the animal's fear of humans, can markedly limit the productivity and welfare of farm animals. This article begins to explore some of the factors that need to be considered to investigate Keeper-Animal Relationships (KARs) in the zoo. In the mid-1990s, a large body of multi-institutional data on zookeepers and animals was collected from 46 Zoos. Using standardized questionnaires, 82 keepers rated how they behaved towards animals, their husbandry routine, how the animal responds to them and to other people, and provided information about themselves. These data include 219 individuals of four endangered species: black rhinoceros, cheetah, maned wolf, and great hornbill. At each zoo, keepers were also videotaped calling to their animals in order to directly observe animal responses to keeper behaviors. Principle Components Analysis reduced eight animal variables to three components and ten keeper variables to five components. Scores for animals and for keepers were calculated on these components and compared, according to five predictions based on models of human-animal interactions in the literature. Animal responses to keepers varied along three dimensions: Affinity to Keeper, Fear of People, and Sociable/Curious. Animal scores of Fear of People were significantly and positively correlated with independent measures of poor welfare from two later studies: fecal corticoid concentrations for 12 black rhinos and "tense-fearful" scores for 12 cheetahs. (1) Significant species differences were found for Affinity to Keeper and Fear of People, and the interaction of these two dimensions of animal response to keepers appears to be species-specific. (2) The quality of KAR is influenced by whether the zookeeper goes in the enclosure with the animal or not, the frequency and time of feeding, and keeper visibility to the animal. Among keepers who go in with their

  8. A radiotracer for In vivo studies of acetylcholinesterase: p-[{sup 18}F]fluorodonepezil

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S. Y.; Choi, Y. S.; Choi, Y.; Kim, S. E.; Lee, K. H.; Kim, B. T. [Samsung Medical Center, Seoul (Korea, Republic of); Lee, J. W. [Seoul National Univ., Seoul (Korea, Republic of)

    1999-05-01

    Alzheimer's disease (AD) is one of senile dementia caused by lack of acetylcholine in central nervous system, and in vivo studies of acetylcholinesterase (AChE) have been carried out using many radiolabeled AChE inhibitors (donepezil, tacrine, physostigmine, CP-126,998, etc). Donepezil, a FDA approved drug for AD is now in clinical use. Therefore, we synthesized and evaluated p-[{sup 18}F]fluorodonepezil in mice. Biodistribution studies demonstrated that p-[{sup 18}F]fluorodonepezil binds non-specifically in vivo and does not suffer from metabolism in mouse brain. This study suggests that radioligands with higher binding affinity may be required to visualize AChE in vivo and further studies are needed to develop better radiotracers.

  9. Can conclusions drawn from phantom-based image noise assessments be generalized to in vivo studies for the nonlinear model-based iterative reconstruction method?

    Science.gov (United States)

    Gomez-Cardona, Daniel; Li, Ke; Hsieh, Jiang; Lubner, Meghan G; Pickhardt, Perry J; Chen, Guang-Hong

    2016-02-01

    Phantom-based objective image quality assessment methods are widely used in the medical physics community. For a filtered backprojection (FBP) reconstruction-based linear or quasilinear imaging system, the use of this methodology is well justified. Many key image quality metrics acquired with phantom studies can be directly applied to in vivo human subject studies. Recently, a variety of image quality metrics have been investigated for model-based iterative image reconstruction (MBIR) methods and several novel characteristics have been discovered in phantom studies. However, the following question remains unanswered: can certain results obtained from phantom studies be generalized to in vivo animal studies and human subject studies? The purpose of this paper is to address this question. One of the most striking results obtained from phantom studies is a novel power-law relationship between noise variance of MBIR (σ(2)) and tube current-rotation time product (mAs): σ(2) ∝ (mAs)(-0.4) [K. Li et al., "Statistical model based iterative reconstruction (MBIR) in clinical CT systems: Experimental assessment of noise performance," Med. Phys. 41, 041906 (15pp.) (2014)]. To examine whether the same power-law works for in vivo cases, experimental data from two types of in vivo studies were analyzed in this paper. All scans were performed with a 64-slice diagnostic CT scanner (Discovery CT750 HD, GE Healthcare) and reconstructed with both FBP and a MBIR method (Veo, GE Healthcare). An Institutional Animal Care and Use Committee-approved in vivo animal study was performed with an adult swine at six mAs levels (10-290). Additionally, human subject data (a total of 110 subjects) acquired from an IRB-approved clinical trial were analyzed. In this clinical trial, a reduced-mAs scan was performed immediately following the standard mAs scan; the specific mAs used for the two scans varied across human subjects and were determined based on patient size and clinical indications. The

  10. A step-by-step guide to systematically identify all relevant animal studies

    Science.gov (United States)

    Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

    2012-01-01

    Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID:22037056

  11. Imaging of Small Vessels Using Photoacoustics: An In Vivo Study

    NARCIS (Netherlands)

    Siphanto, Ronald I.; Kolkman, R.G.M.; Huisjes, A.; Pilatou, M.H.; de Mul, F.F.M.; Steenbergen, Wiendelt; van Adrichem, Leon N.A.

    2004-01-01

    Background and Objectives The ability to correctly visualize the architectural arrangement of microvasculature is valuable to many diverse fields in medicine. In this study, we applied photoacoustics (PA) to obtain high-resolution images of submillimeter blood vessels. - Study Design/Materials and

  12. Study of hypocholesterolemic activity of Algerian Pistacia lentiscus leaves extracts in vivo

    Directory of Open Access Journals (Sweden)

    Mohammed Cheurfa

    Full Text Available Abstract Plants are a large source of new bioactive molecules with therapeutic potentials. However, only a small amount of worldwide plants have been phytochemically investigated. The aqueous and ethanolic extracts of Pistacia lentiscus L., Anacardiaceae, leaves were evaluated for hypocholesterolemic activity in vivo. In this study, hypercholesterolemia was induced in animals by feeding them high cholesterol (1% food. The extracts of P. lentiscus were orally administered at a dose of 200 mg/kg body weight along with a high cholesterol diet for thirty successive days. Lipid parameters such as total cholesterol, triacylglyceride, low density lipoprotein, very low density lipoprotein and high density lipoprotein were measured in the plasma. Total phenol and flavonoid contents were also evaluated. Flavonoid content was found to be more present in the ethanolic extract (8.218 ± 0.009 mg of QE/g compared to the aqueous extract (3.107 ± 0.014 mg of QE/g. The administration of P. lentiscus extracts produced a significant decrease in total cholesterol, triacylglyceride and low density lipoprotein-cholesterol (154.6 ± 18.10, 71.2 ± 4.38 and 99.36 ± 18.77 mg/dl respectively in the ethanolic extract, while the aqueous extract showed a significant decrease in total cholesterol and triacylglyceride (203.6 ± 9.18 and 97.6 ± 3.57 mg/dl respectively. The results of the investigation demonstrated that P. lentiscus leaf extract has hypocholesterolemic properties and might be used for the prevention of hypercholesterolemia associated disorders.

  13. Titanium Implant Impairment and Surrounding Muscle Cell Death Following High-Salt Diet: An In Vivo Study

    Science.gov (United States)

    Lecocq, Mathieu; Felix, Marie-Solenne; Linares, Jean-Marc; Chaves-Jacob, Julien; Decherchi, Patrick; Dousset, Erick

    2016-01-01

    Aim of the study High-salt consumption has been widely described as a risk factor for cardiovascular, renal and bone functions. In the present study, the extent to which high-salt diet could influence Ti6Al4V implant surface characteristic, its adhesion to rat tibial crest, and could modify muscle cell viability of two surrounding muscles, was investigated in vivo. These parameters have also been assessed following a NMES (neuro-myoelectrostimulation) program similar to that currently used in human care following arthroplasty. Results After a three-week diet, a harmful effect on titanium implant surface and muscle cell viability was noted. This is probably due to salt corrosive effect on metal and then release of toxic substance around biologic tissue. Moreover, if the use of NMES with high-salt diet induced muscles damages, the latter were higher when implant was added. Unexpectedly, higher implant-to-bone adhesion was found for implanted animals receiving salt supplementation. Conclusion Our in vivo study highlights the potential dangerous effect of high-salt diet in arthroplasty based on titanium prosthesis. This effect appears to be more important when high-salt diet is combined with NMES. PMID:26761710

  14. Modular endoprosthesis for mandibular reconstruction: a preliminary animal study.

    NARCIS (Netherlands)

    Lee, S.; Goh, B.T.; Tideman, H.; Stoelinga, P.J.W.

    2008-01-01

    The use of a mandibular modular endoprosthesis after segmental resection of part of the body of the mandible was studied. This preliminary study was carried out on four pigs and four monkeys. The devices were made of a titanium alloy and were cemented in the prepared medullary spaces with

  15. Esophageal Endoscopic Submucosal Dissection Assisted by an Overtube with a Traction Forceps: An Animal Study

    Directory of Open Access Journals (Sweden)

    Ken Ohata

    2016-01-01

    Full Text Available Esophageal endoscopic submucosal dissection (ESD is technically difficult. To make it safer, we developed a novel method using overtube with a traction forceps (OTF for countertraction during submucosal dissection. We conducted an ex vivo animal study and compared the clinical outcomes between OTF-ESD and conventional method (C-ESD. A total of 32 esophageal ESD procedures were performed by four beginner and expert endoscopists. After circumferential mucosal incision for the target lesion, structured as the isolated pig esophagus 3 cm long, either C-ESD or OTF-ESD was randomly selected for submucosal dissection. All the ESD procedures were completed as en bloc resections, while perforation only occurred in a beginner’s C-ESD procedure. The dissection time for OTF-ESD was significantly shorter than that for C-ESD for both the beginner and expert endoscopists (22.8±8.3 min versus 7.8±4.5 min, P<0.001, and 11.3±4.4 min versus 5.9±2.5 min, P=0.01, resp.. The frequency and volume of the submucosal injections were significantly smaller for OTF-ESD than for C-ESD (1.3±0.6 times versus 2.9±1.5 times, P<0.001, and 5.3±2.8 mL versus 15.6±7.3 mL, P<0.001, resp.. Histologically, muscular injury was more common among the C-ESD procedures (80% versus 13%, P=0.009. Our results indicated that the OTF-ESD technique is useful for the safe and easy completion of esophageal ESD.

  16. The development of response surface pathway design to reduce animal numbers in toxicity studies.

    Science.gov (United States)

    Dewi, Sagita; Aune, Tore; Bunæs, John A Aasen; Smith, Adrian J; Larsen, Stig

    2014-03-25

    This study describes the development of Response Surface Pathway (RSP) design, assesses its performance and effectiveness in estimating LD50, and compares RSP with Up and Down Procedures (UDPs) and Random Walk (RW) design. A basic 4-level RSP design was used on 36 male ICR mice given intraperitoneal doses of Yessotoxin. Simulations were performed to optimise the design. A k-adjustment factor was introduced to ensure coverage of the dose window and calculate the dose steps. Instead of using equal numbers of mice on all levels, the number of mice was increased at each design level. Additionally, the binomial outcome variable was changed to multinomial. The performance of the RSP designs and a comparison of UDPs and RW were assessed by simulations. The optimised 4-level RSP design was used on 24 female NMRI mice given Azaspiracid-1 intraperitoneally. The in vivo experiment with basic 4-level RSP design estimated the LD50 of Yessotoxin to be 463 μg/kgBW (95% CI: 383-535). By inclusion of the k-adjustment factor with equal or increasing numbers of mice on increasing dose levels, the estimate changed to 481 μg/kgBW (95% CI: 362-566) and 447 μg/kgBW (95% CI: 378-504 μg/kgBW), respectively. The optimised 4-level RSP estimated the LD50 to be 473 μg/kgBW (95% CI: 442-517). A similar increase in power was demonstrated using the optimised RSP design on real Azaspiracid-1 data. The simulations showed that the inclusion of the k-adjustment factor, reduction in sample size by increasing the number of mice on higher design levels and incorporation of a multinomial outcome gave estimates of the LD50 that were as good as those with the basic RSP design. Furthermore, optimised RSP design performed on just three levels reduced the number of animals from 36 to 15 without loss of information, when compared with the 4-level designs. Simulated comparison of the RSP design with UDPs and RW design demonstrated the superiority of RSP. Optimised RSP design reduces the number of animals

  17. The Combination of In vivo 124I-PET and CT Small Animal Imaging for Evaluation of Thyroid Physiology and Dosimetry

    OpenAIRE

    El-Ali, Henrik H.; Martin Eckerwall; Dorthe Skovgaard; Erik Larsson; Sven-Erik Strand; Andreas Kjaer

    2012-01-01

    Objective: A thyroid rat model combining functional and anatomical information would be of great benefit for better modeling of thyroid physiology and for absorbed dose calculations. Our aim was to show that 124I-PET and CT small animal imaging are useful as a combined model for studying thyroid physiology and dose calculation. Methods: Seven rats were subjects for multiple thyroid 124I-imaging and CT-scans. S-values [mGy/MBqs] for different thyroid sizes were simulated. A phantom with sphere...

  18. Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies.

    Science.gov (United States)

    Thomas, Lydia; Zakir, Foziyah; Mirza, Mohd Aamir; Anwer, Md Khalid; Ahmad, Farhan Jalees; Iqbal, Zeenat

    2017-08-01

    In the present study, various nanoemulsions were prepared using Labrafac PG+Triacetin as oil, Tween 80 as a surfactant and polyethylene glycol (PEG 400) as a co-surfactant. The developed nanoemulsions (NE1-NE5) were evaluated for physicochemical characterizations and ex-vivo for skin permeation and deposition studies. The highest skin deposition was observed for NE2 with 46.07% deposition amongst all developed nanoemulsions (NE1-NE5). Optimized nanoemulsion (NE2) had vesicle size of 84.032±0.023nm, viscosity 78.23±22.2 cps, refractive index 1.404. Nanoemulsion gel were developed by incorporation of optimized nanoemulsion (NE2) into 1-3% chitosan and characterized by physical evaluation and rheological studies. Chitosan gel (2%) was found to be suitable for gelation of nanoemulsion based on its consistency, feel and ease of spreadability. The flux of nanoemulsion gel was found 68.88μg/cm2/h as compared to NE2 (76.05μg/cm2/h) is significantly lower suggesting limited skin permeation of curcumin form gel. However, the retained amount of curcumin on skin by gel formulation (980.75±88μg) is significantly higher than NE2 (771.25±67μg). Enhanced skin permeation of NE2 (46.07%) was observed when compared to nanoemulsion gel (31.25%) and plain gel (11.47%). The outcome of this study evidently points out the potential of curcumin entrapped nanoemulsion gel in wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The Value of Animations in Biology Teaching: A Study of Long-Term Memory Retention

    Science.gov (United States)

    2007-01-01

    Previous work has established that a narrated animation is more effective at communicating a complex biological process (signal transduction) than the equivalent graphic with figure legend. To my knowledge, no study has been done in any subject area on the effectiveness of animations versus graphics in the long-term retention of information, a primary and critical issue in studies of teaching and learning. In this study, involving 393 student responses, three different animations and two graphics—one with and one lacking a legend—were used to determine the long-term retention of information. The results show that students retain more information 21 d after viewing an animation without narration compared with an equivalent graphic whether or not that graphic had a legend. Students' comments provide additional insight into the value of animations in the pedagogical process, and suggestions for future work are proposed. PMID:17785404

  20. An Exploratory Study of Animal-Assisted Interventions Utilized by Mental Health Professionals

    Science.gov (United States)

    O'Callaghan, Dana M.; Chandler, Cynthia K.

    2011-01-01

    This study implemented an exploratory analysis to examine how a sample of mental health professionals incorporates specific animal-assisted techniques into the therapeutic process. An extensive review of literature related to animal-assisted therapy (AAT) resulted in the identification of 18 techniques and 10 intentions for the practice of AAT in…

  1. Longitudinal study of Dutch children’s attachment to companion animals

    NARCIS (Netherlands)

    Endenburg, N.|info:eu-repo/dai/nl/086870181; van Lith, H.A.|info:eu-repo/dai/nl/091342422; Kirpensteijn, J.|info:eu-repo/dai/nl/189846992

    2014-01-01

    The goals of the current studies were (1) to develop a new child-companion animal attachment scale; (2) to determine if children are more attached to dogs than to cats; (3) to examine sex and age differences in attachment to companion animals; and (4) to measure stability of children’s attachment to

  2. Regulating Animal Health, Gender and Quality Control: A Study of Veterinary Surgeons in Great Britain

    Science.gov (United States)

    Enticott, Gareth

    2012-01-01

    This paper explores the validity of performance management regimes for quality assuring animal health regulation by comparing the results of tests for bovine tuberculosis (bTB) between male and female vets. In doing so it hopes to present some practical solutions to the regulation of animal disease and encourage further sociological study of the…

  3. Elements of societal perception of farm animal welfare: A quantitative study in the Netherlands

    NARCIS (Netherlands)

    Boogaard, B.K.; Oosting, S.J.; Bock, B.B.

    2006-01-01

    To study societal perception of animal welfare in The Netherlands and to search for intervention possibilities to influence this perception, 1074 randomly selected Dutch respondents completed a questionnaire on animal welfare. We analysed 15 propositions (4-point Likert scale) and through factor

  4. Antimicrobial effect of calcium hydroxide as an intracanal medicament in root canal treatment: a literature review - Part II. in vivo studies

    Directory of Open Access Journals (Sweden)

    Dohyun Kim

    2015-02-01

    Full Text Available The first part of this study reviewed the characteristics of calcium hydroxide (Ca(OH2 and summarized the results of in vitro studies related to its antimicrobial effects. The second part of this review covers in vivo studies including human clinical studies and animal studies. The use of Ca(OH2 as an intracanal medicament represented better histological results in animal studies. However, human clinical studies showed limited antimicrobial effects that microorganisms were reduced but not eliminated through the treatment, and that some species had resistance to Ca(OH2. Most of clinical outcome studies supported that there is no improvement in healing of periapical lesions when Ca(OH2 was applied between appointments. Further studies are required for the antimicrobial effects of Ca(OH2, and search for the ideal material and technique to completely clean infected root canals should be continued.

  5. Zebrafish Tg(hb9:MTS-Kaede): a new in vivo tool for studying the axonal movement of mitochondria.

    Science.gov (United States)

    Bergamin, Giorgia; Cieri, Domenico; Vazza, Giovanni; Argenton, Francesco; Mostacciuolo, Maria Luisa

    2016-06-01

    Deregulation of axonal transport in neurons is emerging as the major cause of many neurodegenerative diseases in human, such as Charcot-Marie-Tooth (CMT) neuropathy. However, little is known about how mitochondria move in vivo and whether cell culture systems truly represent what happens in living animals. Here we describe the generation of a new zebrafish transgenic line that specifically allows to study mitochondrial dynamics in motor neurons and its application to analyse mitochondrial movement in zebrafish models expressing CMT2A causing mutations. The Tol2 transposon system was used to generate a transgenic zebrafish line expressing the photoconvertible fluorescent protein Kaede in mitochondria of motor neurons. Mitochondrial shape and movement were monitored by time-lapse confocal live imaging and measured by kymograph analysis. The effects of two well-known CMT causing mutations, L76P and R94Q substitutions in MFN2, were then investigated with the same methods. We generated the transgenic zebrafish Tg(hb9:MTS-Kaede) line with genetically labelled mitochondria in motor neurons. Kaede protein was correctly and stably targeted to mitochondrial matrix while retaining its photoconvertibility, thus qualifying this model for in vivo studies. Expression of the L76P and R94Q mutations reduced mitochondrial movement in axons and altered mitochondrial distribution in distinct ways. These findings confirm previously published data obtained in cell cultures and strengthen the hypothesis of different mechanism of action of the two MFN2 mutations. Considering the number of neurodegenerative diseases associated to mitochondrial dynamics, the Tg(hb9:MTS-Kaede) zebrafish line is a promising model to study in vivo alterations of mitochondrial transport underlying human diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Noncontact laser photothermal keratoplasty. III: Histological study in animal eyes.

    Science.gov (United States)

    Ren, Q; Simon, G; Parel, J M

    1994-01-01

    Laser photothermal keratoplasty has been studied as a potential refractive procedure. The purpose of this study is to investigate the histological response to various laser treatments including geometrical patterns, radiant exposure levels, and pulse numbers. A noncontact laser photothermal keratoplasty system was used in this study. Epithelial and endothelial response to the laser photothermal keratoplasty annulus treatment pattern were studied on an owl monkey model with a 5-millimeter annulus ring pattern, 8 J/cm2, 25 consecutive pulses at 1 Hz. Epithelial and endothelial response to the laser photothermal keratoplasty spot pattern were then studied and compared on cat and rabbit models for safety monitoring. One pulse and five consecutive pulses of eight different radiant exposures (5.00 J/cm2 to 18.01 J/cm2) were applied on each cornea. A cadaver eye model was used to study the collagen shrinkage induced by the laser spot treatment following the same protocol as the cat and rabbit model. Finally, the biological healing response to the laser photothermal keratoplasty treatment with the optimal laser parameters obtained in our experiment was studied on the cat model. Five cats were treated by the laser photothermal keratoplasty procedure with eight spots on a 3-millimeter ring, 15.6 J/cm2, and 1 pulse. Epithelial and endothelial damage were observed after annulus treatment on an owl monkey's cornea at 8 J/cm2, 25 pulses, and after spot treatment on cat and rabbit corneas at 18.01 J/cm2, five pulses. No endothelial damage was observed on cat corneas for the single pulse treatment at 18.01 J/cm2. For the tissue shrinkage study, no laser photothermal keratoplasty lesion could be detected for a radiant exposure setting below 10.26 J/cm2. Histological cross-sections showed that the five-pulse treatment reached the endothelial layer at a radiant exposure of 13.4 J/cm2, while no single pulse treatment reached the endothelium for the radiant exposure range (5 J/cm2 to

  7. Refining Housing, Husbandry and Care for Animals Used in Studies Involving Biotelemetry

    Science.gov (United States)

    Hawkins, Penny

    2014-01-01

    Simple Summary Biotelemetry, the remote detection and measurement of an animal function or activity, is widely used in animal research. Biotelemetry devices transmit physiological or behavioural data and may be surgically implanted into animals, or externally attached. This can help to reduce animal numbers and improve welfare, e.g., if animals can be group housed and move freely instead of being tethered to a recording device. However, biotelemetry can also cause pain and distress to animals due to surgery, attachment, single housing and long term laboratory housing. This article explains how welfare and science can be improved by avoiding or minimising these harms. Abstract Biotelemetry can contribute towards reducing animal numbers and suffering in disciplines including physiology, pharmacology and behavioural research. However, the technique can also cause harm to animals, making biotelemetry a ‘refinement that needs refining’. Current welfare issues relating to the housing and husbandry of animals used in biotelemetry studies are single vs. group housing, provision of environmental enrichment, long term laboratory housing and use of telemetered data to help assess welfare. Animals may be singly housed because more than one device transmits on the same wavelength; due to concerns regarding damage to surgical sites; because they are wearing exteriorised jackets; or if monitoring systems can only record from individually housed animals. Much of this can be overcome by thoughtful experimental design and surgery refinements. Similarly, if biotelemetry studies preclude certain enrichment items, husbandry refinement protocols can be adapted to permit some environmental stimulation. Nevertheless, long-term laboratory housing raises welfare concerns and maximum durations should be defined. Telemetered data can be used to help assess welfare, helping to determine endpoints and refine future studies. The above measures will help to improve data quality as well as

  8. Effect of irradiation on gene expression of rat liver adhesion molecules. In vivo and in vitro studies

    Energy Technology Data Exchange (ETDEWEB)

    Moriconi, Federico; Malik, Ihtzaz; Ahmad, Ghayyor; Dudas, Joszef; Ramadori, Giuliano [Dept. of Gastroenterology and Endocrinology, Goettingen Univ. (Germany); Rave-Fraenk, Margret; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans [Dept. of Radiotherapy, Goettingen Univ. (Germany)

    2009-07-15

    Background and purpose: Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro. Material and methods: Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology. Results: Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), {beta}{sub 1}-integrin, {beta}{sub 2}-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, {beta}{sub 1}-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), {beta}{sub 2}-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-){alpha}, interleukin-(IL-)1{beta}, or IL-6 plus TNF-{alpha} led to an upregulation of P-selectin, ICAM-1 and VCAM-1. Conclusion: The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of

  9. The impact of environmental enrichment on the outcome variability and scientific validity of laboratory animal studies.

    Science.gov (United States)

    Bayne, K; Würbel, H

    2014-04-01

    It has been widely accepted for some time that species-appropriate environmental enrichment is important for the welfare of research animals, but its impact on research data initially received little attention. This has now changed, as the use of enrichment as one element of routine husbandry has expanded. In addition to its use in the care of larger research animals, such as nonhuman primates, it is now being used to improve the environments of small research animals, such as rodents, which are used in significantly greater numbers and in a wide variety of studies. Concern has been expressed that enrichment negatively affects both experimental validity and reproducibility. However, when a concise definition of enrichment is used, with a sound understanding of the biology and behaviour of the animal as well as the research constraints, it becomes clear that the welfare of research animals can be enhanced through environmental enrichment without compromising their purpose. Indeed, it is shown that the converse is true: the provision of suitable enrichment enhances the well-being of the animal, thereby refining the animal model and improving the research data. Thus, the argument is made that both the validity and reproducibility of the research are enhanced when proper consideration is given to the research animal's living environment and the animal's opportunities to express species-typical behaviours.

  10. ANIMATED COMPUTER GRAPHICS FOR THE STUDY OF MECHANICAL VIBRATIONS

    OpenAIRE

    Crăifăleanu Andrei; ION George Cătălin

    2006-01-01

    The paper presents a computer code developed by the authors for the study of the small oscillations of a system of two pendulums, coupled one to each other, as well as to the fixed element, with linear springs and with linear viscous dampers. The code has an advanced Windows interface.

  11. Binding Studies of Lamotrigine with Sera of Different Animal Species

    African Journals Online (AJOL)

    Erah

    adverse effects such as low clearance, low brain penetration, drug–drug interaction, etc. [6,7]. It has also been pointed out that not only binding equilibrium but also offset rate may influence the efficacy/distribution of the compound [8]. In our previous works, studies were carried out to evaluate the effect of concentration ...

  12. Titanium Implant Impairment and Surrounding Muscle Cell Death Following High-Salt Diet: An In Vivo Study.

    Science.gov (United States)

    Lecocq, Mathieu; Felix, Marie-Solenne; Linares, Jean-Marc; Chaves-Jacob, Julien; Decherchi, Patrick; Dousset, Erick

    2016-01-01

    High-salt consumption has been widely described as a risk factor for cardiovascular, renal and bone functions. In the present study, the extent to which high-salt diet could influence Ti6Al4V implant surface characteristic, its adhesion to rat tibial crest, and could modify muscle cell viability of two surrounding muscles, was investigated in vivo. These parameters have also been assessed following a NMES (neuro-myoelectrostimulation) program similar to that currently used in human care following arthroplasty. After a three-week diet, a harmful effect on titanium implant surface and muscle cell viability was noted. This is probably due to salt corrosive effect on metal and then release of toxic substance around biologic tissue. Moreover, if the use of NMES with high-salt diet induced muscles damages, the latter were higher when implant was added. Unexpectedly, higher implant-to-bone adhesion was found for implanted animals receiving salt supplementation. Our in vivo study highlights the potential dangerous effect of high-salt diet in arthroplasty based on titanium prosthesis. This effect appears to be more important when high-salt diet is combined with NMES.

  13. Application of the moving-actuator type pump as a ventricular assist device: in vitro and in vivo studies.

    Science.gov (United States)

    Lee, H S; Rho, Y R; Park, C Y; Hwang, C M; Kim, W G; Sun, K; Choi, M J; Lee, K K; Cheong, J T; Shim, E B; Min, B G

    2002-06-01

    A moving actuator type pump has been developed as a multifunctional Korean artificial heart (AnyHeart). The pump consists of a moving actuator as an energy converter, right and left sacs, polymer (or mechanical) valves, and a rigid polyurethane housing. The actuator containing a brushless DC motor moves back and forth on an epicyclical gear train to produce a pendular motion, which compresses both sacs alternately. Of its versatile functions of ventricular assist device and total artificial heart use, we have evaluated the system performance as a single or biventricular assist device through in vitro and in vivo experiments. Pump performance and anatomical feasibility were tested using various animals of different sizes. In the case of single ventricular assist device (VAD) use, one of the sacs remained empty and a mini-compliance chamber was attached to either an outflow or inflow port of the unused sac. The in vitro and in vivo studies show acceptable performance and pump behavior. Further extensive study is required to proceed to human application.

  14. MTR and In-vivo 1H-MRS studies on mouse brain with parkinson's disease

    Science.gov (United States)

    Yoon, Moon-Hyun; Kim, Hyeon-Jin; Chung, Jin-Yeung; Doo, Ah-Reum; Park, Hi-Joon; Kim, Seung-Nam; Choe, Bo-Young

    2012-12-01

    The aim of this study was to investigate whether the changes in the magnetization transfer ratio (MTR) histogram are related to specific characteristics of Parkinson's disease (PD) and to investigate whether the MTR histogram parameters are associated with neurochemical dysfunction by performing in vivo proton magnetic resonance spectroscopy (1H-MRS). MTR and in vivo 1H-MRS studies were performed on control mice (n = 10) and 1-methyl-1,2,3,6-tetrahydropyridine intoxicated mice (n = 10). All the MTR and in vivo 1H-MRS experiments were performed on a 9.4 T MRI/MRS system (Bruker Biospin, Germany) using a standard head coil. The protondensity fast spin echo (FSE) images and the T2-weighted spin echo (SE) images were acquired with no gap. Outer volume suppression (OVS), combined with the ultra-short echo-time stimulated echo acquisition mode (STEAM), was used for the localized in-vivo 1H-MRS. The quantitative analysis of metabolites was performed from the 1H spectra obtained in vivo on the striatum (ST) by using jMRUI (Lyon, France). The peak height of the MTR histograms in the PD model group was significantly lower than that in the control group (p early phase of neuronal dysfunction of neurotransmitters.

  15. Photodynamic activity of tetraazachlorin derivate studied in vivo

    Directory of Open Access Journals (Sweden)

    V. I. Ivanova-Radkevich

    2013-01-01

    Full Text Available The results of investigation for photodynamic activity of new tetraazachlorin derivate – tetramethyltribenzotetraazachlorin, synthesized in Research Institute of Organic Intermediates and Dyes. The study was performed on female mice of СВА line. The tumor model was transferred solid ascetic sarcoma S-37. The samples of photosensitizer, previously solubilized in 10% aqueou s solution ofCremophor EL, injected to mice intravenously on the 7th day of tumor growth in dose of 1–2 mg/kg. Two hours later the irradiation of sensitized tumor using light emitting diode device in a maximal wavelength of 755 nm (light power density – 50 mW/cm2, maximal total light dose – 300 J/cm2 was performed. The efficacy of photodynamic therapy was assessed by growth inhibition rates in the study group comparing with control group. The study showed that photodynamic therapy with investigated sample in dose of 2 mg/kg and light dose of 300 J/cm2 significantly inhibited the tumor growth (inhibition rate of 70–80% within 20 days, indicating prospectivity of subsequent investigations of tetraazachlorin as photosensitizer for photodynamic therapy of malignant tumors. 

  16. Titanium Dioxide as an Osteoconductive Material: An Animal Study

    OpenAIRE

    Harshakumar, Karunakaran; Nair, K. Chandrasekharan; Paulose, N. George; Nair, Vivek V.; Prasanth, V.; Krishnan, Aswathi

    2012-01-01

    The purpose of the present study was to evaluate the biocompatibility and osteoconductive potential of pure and pigment forms of titanium dioxide. Pure and pigment forms of titanium dioxide were incorporated into prepared bur holes in the femur bone of rabbits. Implantation was done on six Albino rabbits which were sacrificed at the end of 3rd, 4th and 5th months after implantation. Radiographic, histologic and scanning electron microscopic evaluations of the implanted sites were performed. H...

  17. A study on current risk assessments and guidelines on the use of food animal products derived from cloned animals.

    Science.gov (United States)

    Hur, Sun Jin

    2017-10-01

    The author widely surveyed and analyzed the food safety issues, ethical issues, permits, and approval of animal products from animals cloned by somatic cell nuclear transfer worldwide. As a result of a 2-year survey, the author found that there is no evidence that meat and milk derived from cloned animals or their progeny pose a risk to food safety in terms of genotoxicity, adverse reproductive effects, or allergic reactions. Most countries have not approved meat and milk derived from cloned animals, and their progeny are entering the food supply. To establish the guidelines, the author suggests four principles of safety assessment for meat and milk derived from cloned animals. The four main principles for safety assessment are similarities of chemical composition, adverse reproductive effects, genotoxicity, and allergic reactions under the influence of meat and milk from cloned animals and noncloned counterparts. This principle means that meat and milk derived from a cloned animal are safe if there are no differences in the four safety assessments of meat and milk between cloned animal's progeny and noncloned counterparts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Critical considerations when planning experimental in vivo studies in dental traumatology

    DEFF Research Database (Denmark)

    Andreasen, Jens O; Andersson, Lars

    2011-01-01

    In vivo studies are sometimes needed to understand healing processes after trauma. For several reasons, not the least ethical, such studies have to be carefully planned and important considerations have to be taken into account about suitability of the experimental model, sample size and optimizing...

  19. Image enhancement based on in vivo hyperspectral gastroscopic images: a case study.

    Science.gov (United States)

    Gu, Xiaozhou; Han, Zhimin; Yao, Liqing; Zhong, Yunshi; Shi, Qiang; Fu, Ye; Liu, Changsheng; Wang, Xiguang; Xie, Tianyu

    2016-10-01

    Hyperspectral imaging (HSI) has been recognized as a powerful tool for noninvasive disease detection in the gastrointestinal field. However, most of the studies on HSI in this field have involved ex vivo biopsies or resected tissues. We proposed an image enhancement method based on in vivo hyperspectral gastroscopic images. First, we developed a flexible gastroscopy system capable of obtaining in vivo hyperspectral images of different types of stomach disease mucosa. Then, depending on a specific object, an appropriate band selection algorithm based on dependence of information was employed to determine a subset of spectral bands that would yield useful spatial information. Finally, these bands were assigned to be the color components of an enhanced image of the object. A gastric ulcer case study demonstrated that our method yields higher color tone contrast, which enhanced the displays of the gastric ulcer regions, and that it will be valuable in clinical applications.

  20. Image enhancement based on in vivo hyperspectral gastroscopic images: a case study

    Science.gov (United States)

    Gu, Xiaozhou; Han, Zhimin; Yao, Liqing; Zhong, Yunshi; Shi, Qiang; Fu, Ye; Liu, Changsheng; Wang, Xiguang; Xie, Tianyu

    2016-10-01

    Hyperspectral imaging (HSI) has been recognized as a powerful tool for noninvasive disease detection in the gastrointestinal field. However, most of the studies on HSI in this field have involved ex vivo biopsies or resected tissues. We proposed an image enhancement method based on in vivo hyperspectral gastroscopic images. First, we developed a flexible gastroscopy system capable of obtaining in vivo hyperspectral images of different types of stomach disease mucosa. Then, depending on a specific object, an appropriate band selection algorithm based on dependence of information was employed to determine a subset of spectral bands that would yield useful spatial information. Finally, these bands were assigned to be the color components of an enhanced image of the object. A gastric ulcer case study demonstrated that our method yields higher color tone contrast, which enhanced the displays of the gastric ulcer regions, and that it will be valuable in clinical applications.

  1. An autoradiographic study of bone grafts in small animals.

    Science.gov (United States)

    Hildmann, H; Tiedjen, K U; Hildmann, A

    1986-01-01

    Bone remodelling was studied in allografts and isografts by means of autoradiography. Collagen and proteoglycans of the organic bone matrix were labelled with H-3 amino acids and S-35 sodium sulphate. The principles of primary bone formation are followed in graft remodelling as well. Matrix breakdown and reformation are carried out by mononuclear cells. Components of the original matrix can be seen in osteoclasts, perivascular cells, osteoblasts, young osteocytes, and in new bone. The label allows tracing of these components and proves their reuse.

  2. Autoradiographic study of bone grafts in small animals

    Energy Technology Data Exchange (ETDEWEB)

    Hildmann, H.; Tiedjen, K.U.; Hildmann, A.

    1986-07-01

    Bone remodelling was studied in allografts and isografts by means of autoradiography. Collagen and proteglycanes of the organic bone matrix were labelled with H-3 amino acids and S-35 sodium sulphate. The principles of primary bone formation are followed in graft remodelling as well. Matrix breakdown and reformation are carried out by mononuclear cells. Components of the original matrix can be seen in osteoclasts, perivascular cells, osteoblasts, young osteocytes, and in new bone. The label allows tracing of these components and proves their reuse.

  3. Bone tissue response induced by bioactive polymer functionalized Ti6Al4V surfaces: In vitro and in vivo study.

    Science.gov (United States)

    Felgueiras, Helena P; Decambron, Adeline; Manassero, Mathieu; Tulasne, Louise; Evans, Margaret D M; Viateau, Véronique; Migonney, Véronique

    2017-04-01

    Ti6Al4V is commonly used for orthopedic applications. This study was designed to test the potentially added benefit of Ti6Al4V functionalized with a bioactive polymer poly(sodium styrene sulfonate) both in vitro and in vivo. Cell-based assays with MC3T3-E1 osteoblast-like cells were used to measure the cell adhesion strength, cell spreading, focal contact formation, cell differentiation and the mineralization of extracellular matrix on grafted and ungrafted Ti6Al4V discs in combination with FBS and collagen type I. Bone morphogenetic protein-2 (BMP-2) was also included in the cell differentiation assay. Results showed that the grafted surface combined with collagen I gave superior levels in every parameter tested with cell-based assays and was almost equivalent to BMP-2 for cell differentiation. In vivo testing was conducted in rabbits (n=42) with cylinders of grafted and ungrafted Ti6Al4V implanted in defects made to the femoral and lateral condyles and animals that were maintained to 1, 3 and 12months. Hydroxyapatite coated Ti6Al4V cylinders were included as a clinical reference control. Osseointegration was assessed post-mortem using histomorphometric analysis conducted on resin sections of explanted undecalcified bone. Two histomorphometric parameters, that of bone-to-implant contact and the bone area, were analyzed by a trained observer blinded to sample identity. Results showed osseointegration on grafted Ti6Al4V was marginally better than both ungrafted and hydroxyapatite coated Ti6Al4V. Overall, the study found that the grafted Ti6Al4V significantly promoted all aspects of osteogenesis tested in vitro and, although in vivo outcomes were less compelling, histomorphometry showed osseointegration of grafted Ti6Al4V implants was equivalent or better than controls. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Study of cultured fibroblasts in vivo using NMR

    Energy Technology Data Exchange (ETDEWEB)

    Karczmar, G.S.

    1984-01-01

    The goal of this thesis was to study the compartmentation of phosphorylated glycolytic intermediates in intact Chicken Embryo Fibroblasts (CEFs) using /sup 31/P NMR at 109 MHz. Because glycolysis is regulated differently in normal and virally transformed CEFs, NMR experiments were performed on both types of cells. A technique for maintaining functional cells at high densities in an NMR magnet is described. Signals were detected from cytoplasmic inorganic phosphate (P/sub i/), ATP, NAD, NADH, phosphorylcholine and phosphorylethanolamine. The effect of external glucose on cytoplasmic pools of phosphates was studied. However, experiments with /sup 32/P labelled P/sub i/ showed that as the concentration of glucose in the medium was increased, the amount of phosphate sequestered in the cells increased. They conclude that there is a pool of P/sub i/ which is not detected by high resolution of NMR and that the size of this pool increases as the rate of glycolysis increases. These effects were found only in cultured cells; the data for transformed and normal cells were similar. Longitudinal relaxation times of intracellular phosphates in normal, transformed, and primary CEFs were measured.

  5. Study of cultured fibroblasts in vivo using NMR

    Energy Technology Data Exchange (ETDEWEB)

    Karczmar, G.S.

    1984-08-01

    The goal was to study the compartmentation of phosphorylated glycolytic intermediates in intact Chicken Embryo Fibroblasts (CEFs) using /sup 31/P NMR at 109 MHz. A technique for maintaining functional cells at high densities in an NMR magnet is described. Signals were detected from cytoplasmic inorganic phosphate (P/sub i/), ATP, NAD, NADH, phosphorylcholine and phosphorylethanolamine. The effect of external glucose on cytoplasmic pools of phosphates was studied. When cells were perfused with glucose-free medium the rate of glycolysis decreased, the amplitudes of the ATP resonances decreased, and the P/sub i/ intensity increased. The quantity of NMR-detectable P/sub i/ produced was significantly greater than the quantity of NMR-detectable ATP which was lost. Experiments with /sup 32/P labeled P/sub i/ showed that as the concentration of glucose in the medium was increase, the amount of phosphate sequestered in the cells increased. We conclude that there is a pool of P/sub i/ which is not detected by high resolution NMR and that the size of this pool increases as the rate of glycolysis increase. Longtitudinal relaxation times of intracellular phosphates in normal, transformed, and primary CEFs were measured. The results demonstrate that relaxation times of phosphates are sensitive to structural and metabolic changes which occur when cells are grown in culture. 59 references. 31 figures.

  6. Studies of DNA supercoiling in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Cook, David Nelson [Univ. of California, Berkeley, CA (United States)

    1990-10-01

    This thesis describes a number of diverse experiments whose common theme is to elaborate some aspect of DNA supercoiling. The torsion elastic constant of DNA is measure as a function of superhelix density using the technique of picosecond Time Resolved Fluorescence Polarization Anisotropy (FPA) of intercalated ethidium bromide. The results agree with theories which predict that the anisotropy decay should vary with the square root of the relative viscosity. This experiment furthermore demonstrates a sensitivity of FPA to a change in torsion elastic constant of less than 10%. A number of covalently closed DNA samples, ranging in superhelix density from = -0.123 to +0.042, are then examined. A novel method for measuring changes in local supercoiling on a large PNA molecule which is sensitive to changes in supercoiling of regions of chromosomal DNA as short as 1 kilobase in length is presented. Study of chromosomal supercoiling regulating anaerobic gene expression in the facultative photosynthetic bacterium, Rhodobacter capsulatus showed that no stable change in chromosomal supercoiling upon a shift from aerobic respiratory growth to anaerobic photosynthetic conditions. Studies to detect transient changes in DNA supercoiling indicate that DNA downstream from heavily transcribed genes for the photosynthetic reaction center are relaxed or perhaps overwound upon the induction of photosynthetic metabolism. These results are interpreted in terms of the twin domain model of transcriptional supercoiling.

  7. Studies of DNA supercoiling in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Cook, D.N.

    1990-10-01

    This thesis describes a number of diverse experiments whose common theme is to elaborate some aspect of DNA supercoiling. The torsion elastic constant of DNA is measure as a function of superhelix density using the technique of picosecond Time Resolved Fluorescence Polarization Anisotropy (FPA) of intercalated ethidium bromide. The results agree with theories which predict that the anisotropy decay should vary with the square root of the relative viscosity. This experiment furthermore demonstrates a sensitivity of FPA to a change in torsion elastic constant of less than 10%. A number of covalently closed DNA samples, ranging in superhelix density from = [minus]0.123 to [plus]0.042, are then examined. A novel method for measuring changes in local supercoiling on a large PNA molecule which is sensitive to changes in supercoiling of regions of chromosomal DNA as short as 1 kilobase in length is presented. Study of chromosomal supercoiling regulating anaerobic gene expression in the facultative photosynthetic bacterium, Rhodobacter capsulatus showed that no stable change in chromosomal supercoiling upon a shift from aerobic respiratory growth to anaerobic photosynthetic conditions. Studies to detect transient changes in DNA supercoiling indicate that DNA downstream from heavily transcribed genes for the photosynthetic reaction center are relaxed or perhaps overwound upon the induction of photosynthetic metabolism. These results are interpreted in terms of the twin domain model of transcriptional supercoiling.

  8. Aquatic live animal radiotracing studies for ecotoxicological applications: Addressing fundamental methodological deficiencies.

    Science.gov (United States)

    Cresswell, Tom; Metian, Marc; Golding, Lisa A; Wood, Mike D

    2017-11-01

    The use of live animal gamma radioisotope tracer techniques in the field of ecotoxicology allows laboratory studies to accurately monitor contaminant biokinetics in real time for an individual organism. However, methods used in published studies for aquatic organisms are rarely described in sufficient detail to allow for study replication or an assessment of the errors associated with live animal radioanalysis to be identified. We evaluate the influence of some important methodological deficiencies through an overview of the literature on live aquatic animal radiotracer techniques and through the results obtained from our radiotracer studies on four aquatic invertebrate species. The main factors discussed are animal rinsing, radioanalysis and geometry corrections. We provide examples of three main techniques in live aquatic animal radiotracer studies to improve data quality control and demonstrate why each technique is crucial in interpreting the data from such studies. The animal rinsing technique is also relevant to non-radioisotope tracer studies, especially those involving nanoparticles. We present clear guidance on how to perform each technique and explain the importance of proper reporting of the validation of each technique for individual studies. In this paper we describe methods that are often used in lab-based radioecology studies but are rarely described in great detail. We hope that this paper will act as the basis for standard operating procedures for future radioecology studies to improve study replication and data quality control. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Studying Kinetochores In Vivo Using FLIM-FRET.

    Science.gov (United States)

    Yoo, Tae Yeon; Needleman, Daniel J

    2016-01-01

    Kinetochores play essential roles in coordinating mitosis, as a mechanical connector between chromosome and microtubule and as a source of numerous biochemical signals. These mechanical and biochemical behaviors of kinetochores change dynamically in cells during mitosis. Therefore, understanding kinetochore function requires an imaging tool that quantifies the protein-protein interactions or biochemical changes with high spatiotemporal resolution. FRET has previously been used in combination with biosensors to probe protein-protein interactions and biochemical activity. In this chapter, we introduce FLIM-FRET, a lifetime-based method that quantifies FRET, and describe the use of FLIM-FRET as a method for studying dynamic kinetochore behavior in cells with high spatiotemporal resolution.

  10. Ac magnetic susceptibility study of in vivo nanoparticle biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, L; Veintemillas-Verdaguer, S; Serna, C J; Morales, M P [Instituto de Ciencia de Materiales de Madrid, ICMM-CSIC, Sor Juana Ines de la Cruz 3, Cantoblanco 28049, Madrid (Spain); MejIas, R; Barber, D F [Centro Nacional de BiotecnologIa, CNB-CSIC, Darwin 3, Cantoblanco 28049, Madrid (Spain); Lazaro, F J, E-mail: lucia@icmm.csic.es [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Maria de Luna 3, 50018, Zaragoza (Spain)

    2011-06-29

    We analysed magnetic nanoparticle biodistribution, before and after cytokine conjugation, in a mouse model by ac susceptibility measurements of the corresponding resected tissues. Mice received repeated intravenous injections of nanoparticle suspension for two weeks and they were euthanized 1 h after the last injection. In general, only 10% of the total injected nanoparticles after multiple exposures were found in tissues. The rest of the particles may probably be metabolized or excreted by the organism. Our findings indicate that the adsorption of interferon to DMSA-coated magnetic nanoparticles changes their biodistribution, reducing the presence of nanoparticles in lungs and therefore their possible toxicity. The specific targeting of the particles to tumour tissues by the use of an external magnetic field has also been studied. Magnetic nanoparticles were observed by transmission electron microscopy in the targeted tissue and quantified by ac magnetic susceptibility.

  11. Intravital microscopy to study leukocyte recruitment in vivo.

    Science.gov (United States)

    Pinho, Vanessa; Coelho, Fernanda Matos; Menezes, Gustavo Batista; Cara, Denise Carmona

    2011-01-01

    The intravital microscopy is a valuable tool to capture images of cells in living organisms and to make studies of molecular determinants of leukocyte trafficking easier. Using this technique, we can directly visualize and measure each step of the leukocyte recruitment paradigm, including leukocyte rolling flux, rolling velocity, adhesion, and emigration. Thus, it is possible to understand the process involved in leukocyte homing as well as the cell recruitment to inflammatory tissues. Nowadays, two types of intravital microscopy are used routinely. The light microscopy is used to assess migration of intravascular cells in thin, tissues which must be sufficiently translucent. Epifluorescence microscopy allows the visualization of the microcirculation while permitting the distinction of leukocyte subpopulations in solid organs.

  12. [Animal experiment study of healing of the sutured flexor tendon].

    Science.gov (United States)

    Martini, A K; Blimke, B

    1992-01-01

    The purpose of the present study was to determine whether tendons contain intrinsic cells capable of repair. To accomplish this, rabbit flexor tendons were exposed microsurgically, cut through, resutured and transferred as free transplant into the knee-joint. Immobilisation of the knee-joint will cause progressive formation of adhesions permitting neovascularisation of the transplant. Both is not observed when sutured flexor tendons were put in a knee articulation with full range of joint motion. Transmission electron micrography revealed up to 8 weeks after implantation vital cells and incidences of collagen neosynthesis independently whether adhesions existed or not. Histologically intrinsic repair was confirmed in mobile transplants and mainly initiated by cells of the visceral synovial sheet which form an anatomic-surgical unity with the tendon. In conclusion the importance of the synovial fluid for the tendon nutrition is underlined by the fact that an intrinsic healing of flexor tendon is possible without formation of adhesions.

  13. Titanium dioxide as an osteoconductive material: an animal study.

    Science.gov (United States)

    Harshakumar, Karunakaran; Nair, K Chandrasekharan; Paulose, N George; Nair, Vivek V; Prasanth, V; Krishnan, Aswathi

    2013-06-01

    The purpose of the present study was to evaluate the biocompatibility and osteoconductive potential of pure and pigment forms of titanium dioxide. Pure and pigment forms of titanium dioxide were incorporated into prepared bur holes in the femur bone of rabbits. Implantation was done on six Albino rabbits which were sacrificed at the end of 3rd, 4th and 5th months after implantation. Radiographic, histologic and scanning electron microscopic evaluations of the implanted sites were performed. Heamatologic and soft tissue response to these materials were also evaluated. The results showed that both pure and pigment forms of titanium dioxide are biocompatible and have good osteoconductive properties. It was concluded that titanium dioxide can be effectively used in the augmentation of osseous defects and inadequate ridge forms.

  14. Novel instrumentation to determine peel force in vivo and preliminary studies with adhesive skin barriers.

    Science.gov (United States)

    Krueger, Evan M; Cullum, Malford E; Nichols, Thom R; Taylor, Michael G; Sexton, William L; Murahata, Richard I

    2013-11-01

    Adhesive barriers secure medical devices to skin. Laboratory adhesion models are not predictive of in vivo performance. The objectives of these studies were to validate a novel peel force device, and to investigate relationships between barrier formulations, barrier width, subjective discomfort during barrier removal, and substrates. Three hydrocolloid barrier formulations in three widths were adhered to ethylene/methyl acrylate film (EMA), VITRO-SKIN(®) and human abdominal skin. Peel force was measured using a MTS Insight™ and a cyberDERM Inc. Mini Peel Tester (CMPT). Subjects reported their discomfort. Peel forces were highly correlated between devices and highly dependent on substrate. Data suggested a weak direct association between peel force in vivo and discomfort. The 0.5″-wide barriers had the most precise peel forces measurements in vivo. A weak negative relationship between normalized peel force and barrier width on human skin was found. There was a strong positive relationship between peel force in vivo and on EMA, whereas no correlation was observed with VITRO-SKIN(®). The CMPT correlates with a standard instrument and can advantageously investigate adhesion in vivo. Barrier width and substrate impact the reliability and predictability of peel force measurements. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. High-resolution ex vivo magnetic resonance angiography: a feasibility study on biological and medical tissues

    Directory of Open Access Journals (Sweden)

    Boel Lene WT

    2010-03-01

    Full Text Available Abstract Background In biomedical sciences, ex vivo angiography is a practical mean to elucidate vascular structures three-dimensionally with simultaneous estimation of intravascular volume. The objectives of this study were to develop a magnetic resonance (MR method for ex vivo angiography and to compare the findings with computed tomography (CT. To demonstrate the usefulness of this method, examples are provided from four different tissues and species: the human placenta, a rice field eel, a porcine heart and a turtle. Results The optimal solution for ex vivo MR angiography (MRA was a compound containing gelatine (0.05 g/mL, the CT contrast agent barium sulphate (0.43 mol/L and the MR contrast agent gadoteric acid (2.5 mmol/L. It was possible to perform angiography on all specimens. We found that ex vivo MRA could only be performed on fresh tissue because formalin fixation makes the blood vessels permeable to the MR contrast agent. Conclusions Ex vivo MRA provides high-resolution images of fresh tissue and delineates fine structures that we were unable to visualise by CT. We found that MRA provided detailed information similar to or better than conventional CTA in its ability to visualize vessel configuration while avoiding interfering signals from adjacent bones. Interestingly, we found that vascular tissue becomes leaky when formalin-fixed, leading to increased permeability and extravascular leakage of MR contrast agent.

  16. In vivo longitudinal study of rodent skeletal muscle atrophy using ultrasonography.

    Science.gov (United States)

    Mele, Antonietta; Fonzino, Adriano; Rana, Francesco; Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Giustino, Arcangela; Conte Camerino, Diana; Desaphy, Jean-François

    2016-02-01

    Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultrasonographic volume determined in vivo with either method was linearly correlated to the volume determined ex-vivo from excised muscles as muscle weight-to-density ratio. For both soleus and gastrocnemius muscles, a strong linear correlation was obtained between the ultrasonographic volume and the muscle fiber cross-sectional area determined ex-vivo on muscle cryosections. Thus ultrasonography allowed the longitudinal in vivo evaluation of muscle atrophy progression during hindlimb unloading. This study validates ultrasonography as a powerful method for the evaluation of rodent muscle atrophy in vivo, which would prove useful in disease models and therapeutic trials.

  17. Effect of Physical Exercise and Acute Escitalopram on the Excitability of Brain Monoamine Neurons: In Vivo Electrophysiological Study in Rats.

    Science.gov (United States)

    Dremencov, Eliyahu; Csatlósová, Kristína; Durišová, Barbora; Moravcíková, Lucia; Lacinová, Lubica; Ježováv, Daniela

    2017-07-01

    The antidepressant effect of physical exercise has been reported in several clinical and animal studies. Since serotonin, norepinephrine, and dopamine play a central role in depression, it is possible that the beneficial effects of physical exercise are mediated via monoamine pathways. This study investigates the effects of voluntary wheel running on the excitability of monoamine neurons. Male Sprague-Dawley rats were used in the study. Voluntary wheel running (VWR) rats were housed in individual cages with free access to a running wheel, while control animals were housed in standard laboratory cages. After three weeks, the rats were anesthetized, and in vivo electrophysiological recordings were taken from dorsal raphe nucleus serotonin neurons, locus coeruleus norepinephrine neurons, and ventral tegmental dopamine neurons. VWR stimulated activity in serotonin, but not in norepinephrine or dopamine neurons. Subsequently, acute administration of the selective serotonin reuptake inhibitor escitalopram in control rats led to complete suppression of serotonin neurons; this suppression was reversed by subsequent administration of selective antagonist of serotonin-1A receptors, WAY100135. Escitalopram induced only partial inhibition of serotonin neurons in the VWR rats while WAY100135 increased the firing activity of serotonin neurons above the baseline value. The beneficial effect of physical exercise on mood is mediated, at least in part, via activation of serotonin neurons. Physical exercise can potentiate the response to selective serotonin reuptake inhibitors by increasing the basal firing activity and diminishing selective serotonin reuptake inhibitor-induced inhibition of serotonin neurons.

  18. Numerical Model Study of In Vivo Magnetic Nanoparticle Tumor Heating.

    Science.gov (United States)

    Pearce, John A; Petryk, Alicia A; Hoopes, P Jack

    2017-12-01

    Iron oxide nanoparticles are currently under investigation as heating agents for hyperthermic treatment of tumors. Major determinants of effective heating include the biodistribution and minimum iron oxide loading required to achieve adequate heating at practically achievable magnetic field strengths. These inter-related criteria ultimately determine the practicality of this approach to tumor treatment. Further, in our experience the currently used treatment assessment criterion for hyperthermia treatment-cumulative equivalent minutes at 43 °C, CEM43 -provides an inadequate description of the expected treatment effectiveness. Couple numerical models to experimental measurements to study the relative heating effectiveness described by cell death predictions. FEM numerical models were applied to increase the understanding of a carefully calibrated series of experiments in mouse mammary adenocarcinoma. The numerical model results indicate that minimum tumor loadings between approximately 1.3 to 1.8 mg of Fe per cm3 of tumor tissue are required to achieve the experimentally observed temperatures in magnetic field strengths of 32 kA/m (rms) at 162 kHz. We show that including multiple cell death processes operating in parallel within the numerical models provides valuable perspective on the likelihood of successful treatment. We show and believe that these assessment methods are more accurate than a single assessment figure of merit based only on the comparison of thermal histories, such as the CEM method.

  19. Clindamycin and tetracycline as immunomodulating agents: an in vivo study.

    Science.gov (United States)

    Corrales, I; Suarez, A; Lima, A; Ballestero, S; Gómez-Lus, M L; Prieto, J

    1989-01-01

    The present study was undertaken to determine the effects of clindamycin and tetracycline, both intravenously administered, on antibody response to thymus-dependent antigen (PC-KLH) in BALB/c mice. The immunological parameters evaluated were: DPFC/spleen (direct plaque forming-cells), antibody secretion median rate (PC50), heterogeneity index (Hi), number of total splenic lymphocytes and cellular viability. The results showed that clindamycin (i.v.) increased the humoral response; 28 mg/kg was the dose that showed the greatest enhancement (+73%). The PC50 was not affected by clindamycin but Hi decreased at 28 mg/kg and increased at 2.8 mg/kg doses, although neither result was statistically significant. When tetracycline was given i.v., a slight decrease in the anti-PC DPFC number was observed. Although the PC50 was greater at 10 mg/kg (p less than 0.05), Hi was smaller at the 1 mg/kg dose (p less than 0.05).

  20. Genetic regulation of bone strength: a review of animal model studies

    OpenAIRE

    Adams, Douglas J.; Ackert-Bicknell, Cheryl L

    2015-01-01

    Population- and family-based studies have established that fragility fracture risk is heritable; yet, the genome-wide association studies published to date have only accounted for a small fraction of the known variation for fracture risk of either the femur or the lumbar spine. Much work has been carried out using animal models toward finding genetic loci that are associated with bone strength. Studies using animal models overcome some of the issues associated with using patient data, but cau...

  1. In vivo study of myocardial elastography under graded ischemia conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wei-Ning; Provost, Jean; Konofagou, Elisa E [Department of Biomedical Engineering, Columbia University, New York, NY (United States); Fujikura, Kana [Department of Radiology, Columbia University, New York, NY (United States); Wang Jie, E-mail: ek2191@columbia.edu [Department of Medicine, Columbia University, New York, NY (United States)

    2011-02-21

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  2. In vivo study of myocardial elastography under graded ischemia conditions

    Science.gov (United States)

    Lee, Wei-Ning; Provost, Jean; Fujikura, Kana; Wang, Jie; Konofagou, Elisa E.

    2011-02-01

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  3. An in vivo study on bone formation behavior of microporous granular calcium phosphate.

    Science.gov (United States)

    Dalmônico, G M L; Franczak, P F; Levandowski, N; Camargo, N H A; Dallabrida, A L; da Costa, B D; Gil, O García; Cambra-Moo, O; Rodríguez, M A; Canillas, M

    2017-06-27

    This study was developed based on in vivo investigation of microporous granular biomaterials based on calcium phosphates, involving matrices of β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), biphasic compositions of both phases and a control group. The physicochemical characterization of materials was carried out by X-Ray diffraction (DRX) and mercury porosimetry. Biodegradability, bioactivity and neoformation processes were investigated by Raman spectroscopy, scanning electron microscopy (SEM) and polarized light conducted on biopsies obtained from in vivo tests for periods of 90 and 180 days. These were performed to evaluate the behavior of granular microporous compositions in relation to bone neoformation. Through the performance obtained from in vivo assays, excellent osseointegration and bone tissue neoformation were observed. The results are encouraging and show that the microporous granular biomaterials of HA, β-TCP and biphasic compositions show similar results with perfect osseointegration. Architectures simulating a bone structure can make the difference between biomaterials for bone tissue replacement and repair.

  4. Glycation of wood frog (Rana sylvatica) hemoglobin and blood proteins: in vivo and in vitro studies

    Science.gov (United States)

    MacDonald, Justin A.; Degenhardt, Thorsten; Baynes, John W.; Storey, Kenneth B.

    2010-01-01

    The effects of in vivo freezing and glucose cryoprotectant on protein glycation were investigated in the wood frog, Rana sylvatica. Our studies revealed no difference in the fructoselysine content of blood plasma sampled from control, 27 h frozen and 18 h thawed wood frogs. Glycated hemoglobin (GHb) decreased slightly with 48 h freezing exposure and was below control levels after 7 d recovery, while glycated serum albumin was unchanged by 48 h freezing but did increase after 7 d of recovery. In vitro exposure of blood lysates to glucose revealed that the GHb production in wood frogs was similar to that of the rat but was lower than in leopard frogs. We conclude that wood frog hemoglobin was glycated in vitro; however, GHb production was not apparent during freezing and recovery when in vivo glucose is highly elevated. It is possible that wood frog blood proteins have different in vivo susceptibilities to glycation. PMID:19540217

  5. The effect of standard and transepithelial ultraviolet collagen cross-linking on human corneal nerves: an ex vivo study.

    Science.gov (United States)

    Al-Aqaba, Mouhamed; Calienno, Roberta; Fares, Usama; Otri, Ahmad Muneer; Mastropasqua, Leonardo; Nubile, Mario; Dua, Harminder S

    2012-02-01

    To evaluate the early effect of standard and transepithelial collagen cross-linking on human corneal nerves in donor eyes by ex vivo confocal microscopy and acetylcholinesterase staining. Experimental laboratory investigation. Eight human eye bank corneal buttons (mean age, 73.6 years) were included. Ultraviolet A collagen cross-linking was performed postmortem on 3 corneas with the standard protocol involving epithelial debridement and 4 corneas by the transepithelial approach. One cornea served as a control. Corneal nerves were evaluated using confocal microscopy and acetylcholinesterase histology. Confocal microscopy demonstrated the absence of subbasal nerves in corneas treated by the standard technique. These nerves were preserved in corneas treated by the transepithelial approach. Stromal nerves were visible in both groups. Histology of corneas treated by the standard technique revealed localized swellings of the stromal nerves with disruption of axonal membrane and loss of axonal continuity within the treatment zone. These changes were absent in corneas treated by the transepithelial approach. This study highlights the immediate effects of collagen cross-linking on the corneal nerves in an ex vivo model. The absence of subbasal nerves in the early phase of treatment appears to be attributable mainly to mechanical removal of epithelium, rather than ultraviolet light-induced damage. Localized swelling of the stromal nerves was the main difference between the 2 treatment protocols. Further research on laboratory animals would be necessary to verify these changes over a specified time course without the super-addition of postmortem changes. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. A Salmonella Typhimurium-Typhi genomic chimera: a model to study Vi polysaccharide capsule function in vivo.

    Directory of Open Access Journals (Sweden)

    Angela M Jansen

    2011-07-01

    Full Text Available The Vi capsular polysaccharide is a virulence-associated factor expressed by Salmonella enterica serotype Typhi but absent from virtually all other Salmonella serotypes. In order to study this determinant in vivo, we characterised a Vi-positive S. Typhimurium (C5.507 Vi(+, harbouring the Salmonella pathogenicity island (SPI-7, which encodes the Vi locus. S. Typhimurium C5.507 Vi(+ colonised and persisted in mice at similar levels compared to the parent strain, S. Typhimurium C5. However, the innate immune response to infection with C5.507 Vi(+ and SGB1, an isogenic derivative not expressing Vi, differed markedly. Infection with C5.507 Vi(+ resulted in a significant reduction in cellular trafficking of innate immune cells, including PMN and NK cells, compared to SGB1 Vi(- infected animals. C5.507 Vi(+ infection stimulated reduced numbers of TNF-α, MIP-2 and perforin producing cells compared to SGB1 Vi(-. The modulating effect associated with Vi was not observed in MyD88(-/- and was reduced in TLR4(-/- mice. The presence of the Vi capsule also correlated with induction of the anti-inflammatory cytokine IL-10 in vivo, a factor that impacted on chemotaxis and the activation of immune cells in vitro.

  7. In Vivo Study of Dynamics and Stability of Dendritic Spines on Olfactory Bulb Interneurons in Xenopus laevis Tadpoles.

    Directory of Open Access Journals (Sweden)

    Yu-Bin Huang

    Full Text Available Dendritic spines undergo continuous remodeling during development of the nervous system. Their stability is essential for maintaining a functional neuronal circuit. Spine dynamics and stability of cortical excitatory pyramidal neurons have been explored extensively in mammalian animal models. However, little is known about spiny interneurons in non-mammalian vertebrate models. In the present study, neuronal morphology was visualized by single-cell electroporation. Spiny neurons were surveyed in the Xenopus tadpole brain and observed to be widely distributed in the olfactory bulb and telencephalon. DsRed- or PSD95-GFP-expressing spiny interneurons in the olfactory bulb were selected for in vivo time-lapse imaging. Dendritic protrusions were classified as filopodia, thin, stubby, or mushroom spines based on morphology. Dendritic spines on the interneurons were highly dynamic, especially the filopodia and thin spines. The stubby and mushroom spines were relatively more stable, although their stability significantly decreased with longer observation intervals. The 4 spine types exhibited diverse preferences during morphological transitions from one spine type to others. Sensory deprivation induced by severing the olfactory nerve to block the input of mitral/tufted cells had no significant effects on interneuron spine stability. Hence, a new model was established in Xenopus laevis tadpoles to explore dendritic spine dynamics in vivo.

  8. Revisiting optical clearing with dimethyl sulfoxide (DMSO): in vitro and in vivo studies

    Science.gov (United States)

    McClure, R. Anthony; Stoianovici, Charles; Karma, Sanjeev; Choi, Bernard

    2009-02-01

    Functional optical characterization of disease progression and response to therapy suffers from loss of spatial resolution and imaging depth due to scattering, impacting the ability of researchers to localize and quantify molecular processes. Here we report on the ability of dimethyl sulfoxide (DMSO) to reduce temporarily the optical scattering of skin. Data collected from in vitro phantom images and in vivo fluorescence images demonstrate the potential of this simple method to mitigate the blurring effects of scattering with topical application, which we expect will improve the accuracy and localization of in vivo molecular imaging studies.

  9. In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Renata Martinussi; Barboza, Marycel Figols de; Souza, Adriano Aparecido de; Muramoto, Emiko; Mengatti, Jair; Araujo, Elaine Bortoleti de, E-mail: rmcouto@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

    2008-07-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints that is characterized by the inflammation and proliferation of synovial tissues. Approximately 3% of the adult population in the world is affected by this disease which causes pain, joint immobility and disability. Adyo synovectomy (RSV) is a radiotherapeutic modality where a b--emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy in the treatment of RA and other inflammatory arthropathies. There are several radionuclides available for this purpose such as {sup 177}Lu, {sup 90}Y, {sup 153}Sm, {sup 165}Dy, and {sup 166}Ho. Hydroxyapatite (HA) is one of the preferred particulates for this application because it is the major chemical constituent of skeletal bone and it is converted into Ca and PO4 ions in the body. In addition HA is completely eliminated over a period of six weeks. The aim of this work is to compare the in vivo stability of hydroxyapatite labeled with {sup 177}Lu, {sup 90}Y and {sup 153}Sm in order to determine the influence of the radionuclide on biological pattern. In biological studies, 100mL of labeled HAs suspended in normal saline were injected into normal knee joints of Wistar rats and the retention of the activity into the synovium was determined. Labeled particles were also injected by intravenous and intramuscular administration, to verify the biodistribution in the case of an eventual leakage of the products from the joint. Sequential scintigraphic images were acquired from 1 hour to 7 days p.i. after anesthetizing the animals with ketamine. Hydroxyapatite was radiolabeled by all radionuclides with high yield. {sup 177}Lu-HA, {sup 90}Y-HA and {sup 153}Sm-HA were retained in the joint for 7 days, showing

  10. Computer vision-based diameter maps to study fluoroscopic recordings of small intestinal motility from conscious experimental animals.

    Science.gov (United States)

    Ramírez, I; Pantrigo, J J; Montemayor, A S; López-Pérez, A E; Martín-Fontelles, M I; Brookes, S J H; Abalo, R

    2017-08-01

    When available, fluoroscopic recordings are a relatively cheap, non-invasive and technically straightforward way to study gastrointestinal motility. Spatiotemporal maps have been used to characterize motility of intestinal preparations in vitro, or in anesthetized animals in vivo. Here, a new automated computer-based method was used to construct spatiotemporal motility maps from fluoroscopic recordings obtained in conscious rats. Conscious, non-fasted, adult, male Wistar rats (n=8) received intragastric administration of barium contrast, and 1-2 hours later, when several loops of the small intestine were well-defined, a 2 minutes-fluoroscopic recording was obtained. Spatiotemporal diameter maps (Dmaps) were automatically calculated from the recordings. Three recordings were also manually analyzed for comparison. Frequency analysis was performed in order to calculate relevant motility parameters. In each conscious rat, a stable recording (17-20 seconds) was analyzed. The Dmaps manually and automatically obtained from the same recording were comparable, but the automated process was faster and provided higher resolution. Two frequencies of motor activity dominated; lower frequency contractions (15.2±0.9 cpm) had an amplitude approximately five times greater than higher frequency events (32.8±0.7 cpm). The automated method developed here needed little investigator input, provided high-resolution results with short computing times, and automatically compensated for breathing and other small movements, allowing recordings to be made without anesthesia. Although slow and/or infrequent events could not be detected in the short recording periods analyzed to date (17-20 seconds), this novel system enhances the analysis of in vivo motility in conscious animals. © 2017 John Wiley & Sons Ltd.

  11. Eating frequency, food intake, and weight: a systematic review of human and animal experimental studies

    Directory of Open Access Journals (Sweden)

    Hollie eRaynor

    2015-12-01

    Full Text Available Eating frequently during the day, or grazing, has been proposed to assist with managing food intake and weight. This systematic review assessed the effect of greater eating frequency (EF on intake and anthropometrics in human and animal experimental studies. Studies were identified through the PubMed electronic database. To be included, studies needed to be conducted in controlled settings or use methods that carefully monitored food intake, and measure food intake or anthropometrics. Studies using human or animal models of disease states (i.e., conditions influencing glucose or lipid metabolism, aside from being overweight or obese, were not included. The 25 reviewed studies (15 human and 10 animal studies contained varying study designs, EF manipulations (1 to 24 eating occasions per day, lengths of experimentation (230 min to 28 weeks, and sample sizes (3 to 56 participants/animals per condition. Studies were organized into four categories for reporting results: 1 human studies conducted in laboratory/metabolic ward settings; 2 human studies conducted in field settings; 3 animal studies with experimental periods 1 month. Out of the 13 studies reporting on consumption, 8 (61.5% found no significant effect of EF. Seventeen studies reported on anthropometrics, with 11 studies (64.7% finding no significant effect of EF. Future, adequately powered, studies should examine if other factors (i.e., disease states, physical activity, energy balance and weight status, long-term increased EF influence the relationship between increased EF and intake and/or anthropometrics.

  12. A Retrospective Study of Common Diseases of Animals in a Private ...

    African Journals Online (AJOL)

    A Retrospective Study of Common Diseases of Animals in a Private Clinic in Kaduna Metropolitan. JL Barde, A Garba, MM Gashua, MN Mohammed, A Aliyu, L Saádatu, L Konzing, SJ Awulu, VT Gugong, AH Owada ...

  13. Contribution of animal studies to evaluate the similarity of biosimilars to reference products.

    Science.gov (United States)

    van Meer, Peter J K; Ebbers, Hans C; Kooijman, Marlous; Gispen-de Wied, Christine C; Silva-Lima, Beatriz; Moors, Ellen H M; Schellekens, Huub

    2015-04-01

    The European Union (EU) was the first region to establish a regulatory framework for biosimilars, in which animal studies are required to confirm similarity to a reference product. However, animal studies described in European public assessment reports (EPARs) or marketing authorization applications (MAAs) did not identify clinically or toxicologically relevant differences despite differences in quality, suggesting that animal studies lack the sensitivity to confirm biosimilarity. Scientific advice provided learning opportunities to evolve existing guidance. Altogether, the data support a step-wise approach to develop biosimilars that focuses on quality and clinical efficacy of biosimilar. This approach might be more effective and does not necessarily require animal studies, which is also reflected in new EU draft guidance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Selective in vivo effect of chitosan on fatty acid, neutral sterol and bile acid excretion: a longitudinal study.

    Science.gov (United States)

    Santas, Jonathan; Espadaler, Jordi; Mancebo, Remedios; Rafecas, Magda

    2012-09-15

    Chitosan, a deacetylated form of chitin, is a dietary fibre known for its hypolipidemic properties, which are mainly attributed to its unique cationic characteristics. We studied the selective in vivo effect of chitosan on fat excretion in order to elucidate its hypolipidemic mechanism. A 4-week longitudinal study was conducted in guinea pigs and the effect of chitosan on fat-absorption was compared to that of a soluble fibre: digestion-resistant maltodextrin. Animals were fed with high-fat isocaloric diets containing 12/100g of cellulose, digestion-resistant maltodextrin or chitosan. Subsequently, the excretion of fatty acids, neutral sterols and bile acids was determined. Chitosan selectively reduced fat absorption in comparison to digestion-resistant maltodextrin. The excretion of lauric, myristic and palmitic fatty acids of animals fed with chitosan was more than 10-, 5- and 2-fold higher, respectively, than in the cellulose group, whereas stearic acid excretion was not significantly altered. Oleic, linoleic and α-linolenic acid excretion were also significantly higher (Pacid excretion was only increased by chitosan. Nevertheless, chitosan inhibited the intestinal bioconversion of cholesterol and primary bile acids to secondary metabolites. Hence, these results reveal that chitosan and digestion resistant maltodextrin exert their hypolipidemic activity by different mechanisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Factors that Influence Intake to One Municipal Animal Control Facility in Florida: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Terry Spencer

    2017-06-01

    Full Text Available This qualitative study identified a study area by visualizing one year of animal intake from a municipal animal shelter on geographic information systems (GIS maps to select an area of high stray-dog intake to investigate. Researchers conducted semi-structured interviews with residents of the selected study area to elucidate why there were high numbers of stray dogs coming from this location. Using grounded theory, three themes emerged from the interviews: concerns, attitudes, and disparities. The residents expressed concerns about animal welfare, personal safety, money, and health. They held various attitudes toward domestic animals in the community, including viewing them as pets, pests, or useful commodities (products. Residents expressed acceptance as well as some anger and fear about the situation in their community. Interviewees revealed they faced multiple socioeconomic disparities related to poverty. Pet abandonment can result when pet owners must prioritize human needs over animal needs, leading to increased shelter intake of stray dogs. Community-specific strategies for reducing local animal shelter intake should address the issue of pet abandonment by simultaneously targeting veterinary needs of animals, socioeconomic needs of residents, and respecting attitude differences between residents and shelter professionals.

  16. Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

    Directory of Open Access Journals (Sweden)

    Nabeela Nathoo

    2014-01-01

    Full Text Available There are exciting new advances in multiple sclerosis (MS resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future research. Although gadolinium-enhancing and T2 lesions on MRI have been useful for detecting MS pathology, they are not correlative of disability. Therefore, new MRI methods are needed. Such methods require validation in animal models. The increasing necessity for MRI of animal models makes it critical and timely to understand what research has been conducted in this area and what potential there is for use of MRI in preclinical models of MS. Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS studies that have been carried out in animal models of MS that focus on pathology. We compare the MRI phenotypes of animals and patients and provide advice on how best to use animal MR studies to increase our understanding of the linkages between MR and pathology in patients. This review describes how MRI studies of animal models have been, and will continue to be, used in the ongoing effort to understand MS.

  17. Light-dependent pigment migration in blowfly photoreceptors studied by in vivo CLSM

    NARCIS (Netherlands)

    Stavenga, DG; Leertouwer, HL; Smits, RP

    The light-dependent migration of pigment granules in the soma of fly photoreceptors has been studied in vivo with a fast confocal laser scanning microscope. Images as well as photometric measurements were obtained in the reflection and fluorescence modes. Measurements at the single cell level were

  18. GABAERGIC MODULATION OF STRIATAL CHOLINERGIC INTERNEURONS - AN IN-VIVO MICRODIALYSIS STUDY

    NARCIS (Netherlands)

    DEBOER, P; WESTERINK, BHC

    Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of

  19. An experimental model to study isolated effects of thrombin in vivo.

    NARCIS (Netherlands)

    Siller-Matula, J.M.; Bayer, G.; Bergmeister, H.; Quehenberger, P.; Petzelbauer, P.; Friedl, P.H.A.; Mesteri, I.; Jilma, B.

    2010-01-01

    BACKGROUND: In addition to a recognized role in the coagulation cascade and haemostasis, thrombin is known to have multiple functions. We hypothesized that protracted intravenous infusion of thrombin at steady state will allow to study isolated thrombin effects in vivo. METHODS: Thrombin

  20. Current Studies of Acupuncture in Cancer-Induced Bone Pain Animal Models

    OpenAIRE

    Ryu, Hee Kyoung; Baek, Yong-Hyeon; Park, Yeon-Cheol; Seo, Byung-Kwan

    2014-01-01

    Acupuncture is generally accepted as a safe and harmless treatment option for alleviating pain. To explore the pain mechanism, numerous animal models have been developed to simulate specific human pain conditions, including cancer-induced bone pain (CIBP). In this study, we analyzed the current research methodology of acupuncture for the treatment of CIBP. We electronically searched the PubMed database for animal studies published from 2000 onward using these search terms: (bone cancer OR can...

  1. Real-Time Amperometric Recording of Extracellular H2O2 in the Brain of Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study

    Science.gov (United States)

    Reid, Caroline H.; Finnerty, Niall J.

    2017-01-01

    We detail an extensive characterisation study on a previously described dual amperometric H2O2 biosensor consisting of H2O2 detection (blank) and degradation (catalase) electrodes. In vitro investigations demonstrated excellent H2O2 sensitivity and selectivity against the interferent, ascorbic acid. Ex vivo studies were performed to mimic physiological conditions prior to in vivo deployment. Exposure to brain tissue homogenate identified reliable sensitivity and selectivity recordings up to seven days for both blank and catalase electrodes. Furthermore, there was no compromise in pre- and post-implanted catalase electrode sensitivity in ex vivo mouse brain. In vivo investigations performed in anaesthetised mice confirmed the ability of the H2O2 biosensor to detect increases in amperometric current following locally perfused/infused H2O2 and antioxidant inhibitors mercaptosuccinic acid and sodium azide. Subsequent recordings in freely moving mice identified negligible effects of control saline and sodium ascorbate interference injections on amperometric H2O2 current. Furthermore, the stability of the amperometric current was confirmed over a five-day period and analysis of 24-h signal recordings identified the absence of diurnal variations in amperometric current. Collectively, these findings confirm the biosensor current responds in vivo to increasing exogenous and endogenous H2O2 and tentatively supports measurement of H2O2 dynamics in freely moving NOD SCID mice. PMID:28698470

  2. Real-Time Amperometric Recording of Extracellular H₂O₂ in the Brain of Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study.

    Science.gov (United States)

    Reid, Caroline H; Finnerty, Niall J

    2017-07-08

    We detail an extensive characterisation study on a previously described dual amperometric H₂O₂ biosensor consisting of H₂O₂ detection (blank) and degradation (catalase) electrodes. In vitro investigations demonstrated excellent H₂O₂ sensitivity and selectivity against the interferent, ascorbic acid. Ex vivo studies were performed to mimic physiological conditions prior to in vivo deployment. Exposure to brain tissue homogenate identified reliable sensitivity and selectivity recordings up to seven days for both blank and catalase electrodes. Furthermore, there was no compromise in pre- and post-implanted catalase electrode sensitivity in ex vivo mouse brain. In vivo investigations performed in anaesthetised mice confirmed the ability of the H₂O₂ biosensor to detect increases in amperometric current following locally perfused/infused H₂O₂ and antioxidant inhibitors mercaptosuccinic acid and sodium azide. Subsequent recordings in freely moving mice identified negligible effects of control saline and sodium ascorbate interference injections on amperometric H₂O₂ current. Furthermore, the stability of the amperometric current was confirmed over a five-day period and analysis of 24-h signal recordings identified the absence of diurnal variations in amperometric current. Collectively, these findings confirm the biosensor current responds in vivo to increasing exogenous and endogenous H₂O₂ and tentatively supports measurement of H₂O₂ dynamics in freely moving NOD SCID mice.

  3. Biocompatibility assessment of modified Portland cement in comparison with MTA® : In vivo and in vitro studies

    Directory of Open Access Journals (Sweden)

    I Khalil

    2012-01-01

    Full Text Available Aim: The aim of our study is to elaborate a new cement based on Portland cement (PC, Modified Portland Cement (MPC with modified chemical and physical properties that allow easier clinical manipulation and faster setting time than MTA® and then to evaluate its cytotoxicity in vitro and its biocompatibility in vivo in comparison with MTA® . Materials and Methods: Elaboration of MPC: Portland cement powder slenderly grinded to homogenize the particles, mixed with a radiopaque element and a setting time accelerator. A comparative in vitro study (MTS test of the toxic effect of MTA® and MPC with culture isolated from the calvaria of 18-day-old fetal Swiss OF1 mice are done. A comparative in vivo study of the biocompatibility of MTA® and MPC: Under general anaesthesia, three holes (2.5 mm were made in both the left and right femurs of six White New Zealand rabbits. In the first hole MPC is placed, in the second MTA® and the third one is left empty (negative control group. Three weeks after implantation, two rabbits are sacrificed, then two other rabbits over six weeks and the last two after twelve weeks. The neck of the femur is trimmed and prepared for undecalcified histological studies. Mann-Whitney test was used to analyze the results. Results: The cell viability test according to the morphological observations suggested the biocompatibility of the two biomaterials tested. The in vivo test showed similar biocompatibility between MTA® and MPC. Bone healing and minimal inflammatory response adjacent to MTA® and MPC implants were observed at all experimental periods (3, 6 and 12 weeks, suggesting that both materials are well tolerated. Conclusion: This pilot comparative study of MTA® and MPC showed no or very limited toxic effects of both cements in vitro and similar biocompatibility in vivo. However, additional in vivo and clinical studies should be done on MPC before it can be introduced in our clinical practice.

  4. IN-VIVO DIAGNOSIS OF CHEMICALLY INDUCED MELANOMA IN AN ANIMAL MODEL USING UV-VISIBLE AND NIR ELASTIC SCATTERING SPECTROSCOPY: PRELIMINARY TESTING.

    Energy Technology Data Exchange (ETDEWEB)

    C. A' AMAR; R. LEY; ET AL

    2001-01-01

    Elastic light scattering spectroscopy (ESS) has the potential to provide spectra that contain both morphological and chromophore information from tissue. We report on a preliminary study of this technique, with the hope of developing a method for diagnosis of highly-pigmented skin lesions, commonly associated with skin cancer. Four opossums were treated with dimethylbenz(a)anthracene to induce both malignant melanoma and benign pigmented lesions. Skin lesions were examined in vivo using both UV-visible and near infrared (NIR) ESS, with wavelength ranges of 330-900 nm and 900-1700 n