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William, V. G., Володимир Миколайович Дейнека, Владимир Николаевич Дейнека, Volodymyr Mykolaiovych Deineka, R. Gwendolen, Максим Володимирович Погорєлов, Максим Владимирович Погорелов et Maksym Volodymyrovych Pohorielov. « In-vivo testing of spongy titanium implant biocompatibility ». Thesis, Сумський державний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/31970.
Texte intégralRésumé :
The conducted experiment shows porous titanium implant biocompatibility and existence of conductive features. This results leads to further research concerning this materials possible usage in osteoplasty.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/31970
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Cantu, Mark. « Shortened in Vivo Bioconcentration Factor Testing in Cyprinus Carpio ». Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407781/.
Texte intégralRésumé :
Bioconcentration factor testing serves as the most valuable surrogate for the assessment of bioaccumulation. The assessment of potentially harmful chemicals is crucial to not only the health of aquatic environments, but to humans as well. Chemicals that possess the ability to persist in the environment or that have the potential to bioaccumulate, pose a greater risk to organisms that are exposed to these chemicals. The Organization for Economic Cooperation and Development Guideline 305 outlines specific protocols to run an accurate and reliable aquatic flow-through test. However, since its adoption in 1996, very few changes have been made to accommodate the endeavor to lowering the amount of test species to run one of these said tests. Running an aquatic flow-through test, according to 305, takes much time and money as well as numerous amounts of fish. Such burdens can be eliminated through simple modifications to the standard protocols. In this study, we propose an abbreviated study design for aquatic bioconcentration testing which effectively alleviates the burdens of running a flow-through test. Four chemicals were used individually to evaluate the usefulness of the proposed shortened design; 4-Nonyphenol, Chlorpyrifos, Musk Xylene, and DDT. The study consisted of exposing Cyprinus carpio for 7 days followed by 7 days of depuration, for a total of a 14-day study. Our results for each of the four compounds are consistent with literature values, thus, demonstrating that BCFk can be accurately predicted in an abbreviated in vivo test.
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GAZZOLA, LUCA. « Field Testing of Software Applications ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241221.
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Quando interagiscono con sistemi software, gli utenti potrebbero dover affrontare problemi come crash, fallimenti e instabilità del programma. Il software difettoso in esecuzione sul campo non è solo la conseguenza di tecniche di verifica inefficaci, ma è anche dovuto alla complessità e alla diversità delle interazioni tra un'applicazione e il suo ambiente. Molte di queste interazioni sono difficilmente previste al momento del test, e anche quando potrebbero essere previste, spesso ci sono così tanti casi da testare che non possono essere affrontati in modo fattibile prima che il software sia rilasciato.
Il testing sul campo si propone di affrontare il problema dei fallimenti delle applicazioni sul campo spostando la fase di test direttamente nell'ambiente di produzione. Ciò rende possibile sfruttare diversi scenari che altrimenti sarebbero difficili da catturare con test tradizionali.
In questa tesi esploriamo l'area del testing sul campo del software, presentiamo uno studio che caratterizza il problema delle applicazioni che falliscono sul campo, un'architettura client-server che può essere sfruttata per organizzare e controllare il processo di test sul campo e un approccio di test che sfrutta l’ambiente di produzione come banco di prova per l'esecuzione dei test case. L'approccio presentato viene valutato empiricamente su un dataset di errori del software, dimostrando che il 35% dei guasti non rilevati internamente potrebbe essere stato rivelato con test sul campo.When interacting with their software systems, users may have to deal with problems like crashes, failures, and program instability. Faulty software running in the field is not only the consequence of ineffective in-house verification and validation techniques, but it is also due to the complexity and diversity of the interactions between an application and its environment. Many of these interactions can be hardly predicted at testing time, and even when they could be predicted, often there are so many cases to be tested that they cannot be all feasibly addressed before the software is released. Field testing aims to tackle the problem of applications failing in the field by moving the testing phase directly in the field environment. This makes it possible to exploit different scenarios that would otherwise be difficult to capture with in-house testing. In this Ph.D. thesis we explore the area of software field testing, we present a study that characterizes the problem of applications failing in the field, a client-server architecture that can be exploited to organize and control the field testing process and a testing approach that exploits the field itself as testbed for running the test cases. The presented approach is empirically evaluated on a popular dataset of software faults demonstrating that 35% of the faults that were not discovered in-house could have been revealed with field testing.
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Charenkavanich, Panasaya. « Calibration of sonographic gel probe covers for in-vivo mechanical testing ». Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/32870.
Texte intégralRésumé :
Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2005.Includes bibliographical references (leaf 29).
Cervical insufficiency is a condition in pregnancy in which the cervix asymptomatically dilates in the absence of uterine contractions, resulting in a spontaneous preterm delivery. The condition is often misdiagnosed and presents a significant challenge for the clinical community. In order to establish better diagnostic criteria for cervical insufficiency and to improve assessment of preterm delivery risk for the individual patient, a non-invasive medical imaging tool, which uses ultrasound elastography to test the mechanical properties of cervical tissue, has been developed. The hand-held ultrasound indentation system will enable in vivo collection of stress-strain data from patients that will provide researchers with the necessary information to be used in material modeling and improve diagnosis of cervical insufficiency. The device consists of an ultrasound probe, enclosed by a gel-filled cover. The mechanical properties of the covers vary with each cap as well as with time and temperature. Therefore, in order to ensure accurate measurement, the probe covers must be calibrated prior to use. An experimental study was carried out to examine the effects of various testing conditions on the mechanical behavior of the probe covers. Different freezing and thawing techniques were explored in order to determine favorable conditions in order to preserve the integrity of the probes between the time of manufacture and actual use. From the results of the research, the appropriate combination of testing conditions for probe calibration was determined, as well as freezing and thawing techniques for probe preservation.
by Panasaya Charenkavanich.
S.B.
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Caminal, Bobet Marta. « Tissue engineering for bone regeneration : in vitro development and in vivo testing in sheep ». Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/285622.
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L'os és un teixit connectiu altament organitzat i especialitzat, la funció principal és la mecànica, proporcionant l'afecció als músculs i per tant permetent que el cos es mogui. Actualment, el tractament quirúrgic estàndard es basa en la immobilització i la introducció d'empelts ossis però presenta algunes complicacions, com ara les infeccions, les no unions i la morbiditat de la zona donant. Avui en dia, milions de pacients pateixen defectes ossis i en concret, als EEUU es diagnostiquen entre 10.000 i 20.000 nous casos d'osteonecrosi del cap de fèmur (ONFH) a l’any.
La medicina regenerativa (RM) i l'enginyeria tissular (TE) són dos camps de la ciència que es centren en el desenvolupament de teràpies per reemplaçar i regenerar els teixits perduts o danyats per millorar la qualitat de vida del pacient. La combinació de biomaterials, cèl·lules i senyals és l’eina clau per al desenvolupament d'un producte RM i TE. Un dels camps més desenvolupats en RM és la medicina regenerativa ortopèdica, en concret per al teixit ossi. Hi ha diferents estratègies que combinen cèl·lules autòlogues amb matrius que han demostrat certa eficàcia en el tractament de lesions òssies. Després de la fase de descobriment de nous medicaments de teràpia avançada, i per tal d’aconseguir el registre del nou producte, hi ha la fase de desenvolupament, que inclou la realització d'estudis preclínics (fet per dur a terme la prova de concepte, la seguretat i toxicologia) i els estudis clínics.
En primer lloc es van determinar i caracteritzar els components de la preparació d’enginyeria tissular (TEP) amb la finalitat d’obtenir un producte estandarditzat. Aquesta preparació consisteix en un component cel·lular que són les cèl·lules mesenquimals estromals (MSC), tant humanes com ovines unides en una matriu de partícules òssies desantigeneïtzades i liofilitzades.
Es va realizar un model de defecte ossi de mida crítica (CSBD) en ovella amb la finalitat d'investigar l'efecte de la TEP en una situació extrema, i es va demostrar la seva seguretat i capacitat per sintetitzar nou os i remodelar l’os existent.
Seguidament la TEP es va provar en un model animal rellevant de translació de la malaltia òssia basat en el mètode reportat per Vélez i col·laboradors per a la modelització de ONFH en ovelles demostrant la seva eficàcia i seguretat. També s’ha demostrat que les MSC estan involucrades en la síntesi d'os nou ja que es van trobar progenitors ossis marcats després del tractament de la ONFH, tot i així no es poden descartar els mecanismes paracrins.
Per tant, el desenvolupament de la TEP podria contribuir en general a la RM per tal de satisfer les exigències d'una societat que envelleix.Bone is a highly organized and specialized connective tissue, whose main function is the mechanics, providing attachment to muscles and therefore allowing the body to move. Currently the gold standard surgical treatment is based on the immobilization and introduction of bone grafts but it presents some complications, such as infections, non-unions, and donor site morbidity. Nowadays, millions of patients are suffering from bone defects and specifically, 10,000 to 20,000 new cases of osteonecrosis of femoral head (ONFH) are diagnosed only in the USA every year. Regenerative medicine (RM) and tissue engineering (TE) are two areas of science fields focused on the developing of therapies to replace and regenerate lost or damaged tissues to improve the quality of life the patient. The combination of biomaterials, cells and signals is the key tool for the development of a RM and TE product. One of the most developed fields in RM is the orthopedic regenerative medicine, in specifically for bone tissue. There are different strategies combining autologous cells with scaffolds that have shown some efficacy for treating bone injuries. After discovery phase of any new advanced therapy medicinal products, there is the development phase that includes the conduction of preclinical studies (made to perform the proof of concept, safety and toxicology) and clinical studies before the registration of the new product. First the components of the tissue engineered preparation (TEP) were determined and characterized in order to have a standardized material. It consists in MSC (mesenchymal stromal cells) both human and ovine sources are used as a cellular component seeded in a deantigenized and lyophilized bone particles as a scaffold. Then critical size bone defect (CSBD) was modeled in sheep in order to investigate the effect of the TEP in an extreme situation, demonstrating its safe ability to synthesize new bone and bone remodeling. Afterwards TEP was tested in a relevant translational animal model of bone disease based on the method reported by Velez and collaborators for modelling ONFH in sheep demonstrating its efficacy and safety. Also demonstrating that MSC were involved in the synthesis of new bone, because labeled bone progenitors are shown after ONFH treatment, although paracrine mechanisms can not be discarded. Therefore, the development of TEP could contribute to the overall RM to meet the requirements of an aging society.
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Kandala, Bala Subramanya Pavan Kumar. « Design, Fabrication, and Testing of Photo-chemically Etched Biodegradable Stents ». University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1593171197849115.
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Deblock, Michael C. « The Synthesis, In Vitro and In Vivo Testing of Silver N-Heterocyclic Carbenes and Imidazolium Complexes ». University of Akron / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=akron1353951003.
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Giesige, Carlee Rae. « Mouse model characterization and in vivo testing of gene therapies for Facioscapulohumeral Muscular Dystrophy ». The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu153193150617187.
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Yamada, Tomoyuki. « In-vivo testing of a magnetically suspended centrifugal pump designed for long-term use ». Kyoto University, 1999. http://hdl.handle.net/2433/181755.
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Tan, J. J. « Cardiosphere-derived stem cell culture, characterisation and labelling for in vivo testing in the infarcted heart ». Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:d902b4f4-6e32-45dd-9767-8e0a17967393.
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Cardiac stem cells (CSCs), isolated from heart tissue explants and expanded via the formation of cardiospheres (Csp), are a promising candidate for cell therapy to prevent heart failure following myocardial infarction. To allow early administration to patients, isolation and expansion of CSCs must be performed in the shortest time possible. Hence, this project aimed to optimize culture conditions and characterize the cardiac explant-derived cells (EDCs), Csp and Csp-derived cells (CDCs) produced. Rat neonatal EDCs contained 4-7% c-kit+ cells, measured using flow cytometry. Optimal Csp growth conditions were determined, such that plating 3 x 10^4 EDCs per well of a 24-well plate coated with 16.7 µg/ml poly-D-lysine, in CGM containing 7% serum, improved Csp production and generated 1.5 x 10^7 CDCs in 16 days, a sufficient number for cell therapy. The CDCs expressed the stemness markers; c-kit, Oct3/4, SOX2, and Klf-4, and the cardiac differentiation markers; GATA4 and Nkx2.5. The therapeutic effect of CDCs may be limited by the low, 3 ± 0.1%, c-kit+ cell numbers. To increase c-kit+ cells in CDCs, an alternate culture method for Csp and different extracellular matrices (ECM) for cell expansion were tested. The hanging drop culture method produced Csp with higher levels of c-kit+ cells (9 ± 2%) than poly-D-lysine-coated and low-bind culture dishes. Of five ECM tested, collagen IV was found to enhance EDC migration and CDC proliferation, and produced 11 ± 0.4% c-kit+ cells, with Csp cultured in hanging drops. Intramyocardial injection of CDCs improved left ventricular ejection fractions of infarcted rat hearts by 9% and prevented the peri-infarct wall from thinning, measured in vivo using MRI over 16 weeks. To improve cell tracking using MRI, two MR positive contrast agents, gadolinium-DTPA and gadonanotubes were tested. Gd-DTPA had low sensitivity after labelling (1.4 x 10^5 cells/mm2); whereas gadonanotubes did not provide positive contrast at 11.7 T. Thus, neither contrast agent could be used for cell tracking using high magnetic field. In conclusion, CDCs were an effective source of stem cells that could be used for heart repair, although cells could not be tracked using positive MR contrast.
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Lee, Chun-kei, et 李鎮基. « Development of an in vivo animal model for testing of endodontic medicaments on pulp tissue ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31954182.
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Lee, Chun-kei. « Development of an in vivo animal model for testing of endodontic medicaments on pulp tissue ». Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk:8888/cgi-bin/hkuto%5Ftoc%5Fpdf?B23300462.
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Hornsby, Jack. « Bladder microstructural and biomechanical modelling : in vivo, in vitro and in silico ». Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:634324ed-851a-4959-adbd-fb45f05a27b6.
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Lower urinary tract disorders are significant prognostic indicators of institutionalisation and lower quality of life in the elderly and their incidence increases with age. Urodynamics, the gold standard in diagnosis, replicates symptoms to assess functionality through controlled filling and voiding of the bladder but its interpretation is subjective and may be inconclusive; often requiring further testing or leading to inappropriate treatment. Normal filling and voiding biomechanics of the bladder relate directly to the structural composition of the bladder wall. Alterations to tissue composition in aging and pathology have significant impacts on biomechanics but are yet to be fully described. The aim of this thesis was to gain insight into the individual microstructural components of the bladder wall and how they relate to the gross mechanical response. Additionally, representation of these observations in a mathematical model that can be used to improve our understanding of urodynamic data. This aim was achieved through a combination of in situ mechanical testing and the development of a microstructural constitutive model, which was then included within an overall micturition framework to simulate filling and voiding functions, and evaluated with clinical data. Coupled systems of multiphoton microscopy and uniaxial, biaxial and inflation testing were used to correlate extra cellular matrix interactions with the mechanical response of young and aged murine bladder. Wall-layer specific collagen fibre orientation, dispersion and recruitment were quantified and implemented into a novel microstructural constitutive model. The bladder was modelled as a nonlinear elastic, constrainedmixture planar membrane with contribution from smooth muscle and collagen fibres in the detrusor. Collagen recruitment in the detrusor was observed to occur at a finite stretch; correlated with a steep increase in stiffness of the tissue, while collagen of the lamina propria plays a capacitance role. Collagen recruitment was modelled using a triangular probability density function; quantified from sequential microscopy images and fitted to mechanical data. Increased collagen area fraction and changes in dominant fibre orientation were attributed to reduced compliance in aged bladder. This behaviour was captured by the model. The microstructural model was modified to an isotropic thin-walled spherical membrane for the filling phase of a micturition model framework, consisting of a bladder outlet relation and urethral resistance relation. A contractile smooth muscle element was included in the active response. In the first steps towards clinical application the model was applied to male and female 'normal' patient urodynamic data to observe quality of model fit and estimate baseline parameter values. The model simulated key filling and voiding features seen in normal male and female clinical data. Mechanobiological modelling combined with clinically relevant micturition modelling has the potential to quantify bladder dysfunction. Moreover, improved understanding of how the microstructure influences macroscopic mechanics will yield improved understanding of how changes to the bladder impair its functionality. We predict that modelling will become a clinically relevant tool in urodynamics; leading to new options for diagnosis and management of patients with bladder dysfunction.
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Berekally, Thomas L. « Some aspects of Maryland Bridge treatments : an 'in-vivo' and 'in-vitro' study ». Title page, contents and summary only, 1989. http://web4.library.adelaide.edu.au/theses/09DM/09dmb487.pdf.
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Ramineni, Sandeep K. « MUCOADHESIVE FILMS FOR TREATMENT OF LOCAL ORAL DISORDERS : DEVELOPMENT, CHARACTERIZATION AND IN VIVO TESTING ». UKnowledge, 2014. http://uknowledge.uky.edu/cbme_etds/19.
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Mucoadhesive drug delivery systems which are being used from 1980’s to avoid first pass metabolism of drugs, commercially exist for only systemic drug delivery with fast erosion times (15-60 min), that may not be appropriate for local oral disorders. The goal of this research was to develop and characterize mucoadhesive films with flexibility of carrying different drugs and proteins and provide sustained release for local treatment of oral disorders.
Mucoadhesive films composed of polyvinylpyrrolidone (PVP) and carboxymethlycellulose (CMC) were formulated with imiquimod, an immune response modifier. Problems such as solubilization of imiquimod to increase drug loading, uniformity in films and total amount of drug released into supernatants were addressed by use of acetate buffer after investigating multiple methods.
Subsequently, other relevant properties of mucoadhesive systems, such as adhesion (shear, pull-off), tensile properties, swelling profiles, transport kinetics, and subsequent changes in release profiles as a function of film composition were characterized. The potential of the system for local retention of imiquimod, determined in oral mucosa of hamsters showed time dependent decrease in imiquimod amount through 12 hours, with no traces of drug in blood. Further testing in humans revealed that the residence time of the mucoadhesive films depended on the application site, increasing in the order of tongue < cheek < gingiva.
In parallel, mucoadhesive films loaded with epidermal growth factor (EGF) were developed to promote treatment of oral mucosal wounds. Bioactivity was tested in vitro on buccal tissues by creating a wound followed by application of films. Although EGF-loaded films did not accelerate wound healing, but rather elicited a hyperparakeratotic response. In vitro buccal tissues may not be appropriate for testing the effects of EGF in wound healing without incorporation of other biochemical factors.
Overall, a mucoadhesive system capable of delivering bioactive small molecules and proteins in sustained manner was developed in this work. A thorough understanding of the system properties was achieved to further tune for future applications. In vitro studies and in vivo studies in hamsters and humans clearly showed the potential and usefulness of the system to translate in to clinic for treatment of oral precancerous lesions.
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Nezafati, Maysam. « Biomaterial Testing Methodology for Long-Term in vivo Applications : Silicon Carbide Corrosion Resistance, Biocompatibility and Hemocompatibility ». Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5283.
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Biomedical devices that function in-vivo offer a tremendous promise to improve the quality of life for many who suffer from disease and trauma. The most important consideration for these devices is that they interact with the physiological environment as designed without initiating a deleterious inflammatory response. ISO 10993 outlines the current international guideline for investigating the biocompatibility of such devices. Numerous groups report the use of ISO 10993 as the basis for their experimental evaluation of candidate materials for neuroprosthetics, as well as other biomedical devices, however most of these reports fail to completely comply with the standard. This leads to a lack of consistent results between R&D groups, which hinders progress in the implantable biomedical device field. For the first time, and to the best of our knowledge, we present a methodology that is in strict adherence to the methodologies presented in ISO 10993, namely direct contact and extract testing. In addition we show that the MTT assay, which has been used in multiple reports, suffers from a major flaw that can create false results especially for conductive materials. We also report on our application of ISO 10993-12 with respect to control materials and preparation methods. These materials are gold and polyethylene as negative reaction controls, and copper and polyvinyl chloride organotin (PVC-org. Sn) as positive reaction controls. The results of our tests are consistent to what has been previously reported, albeit in separate reports. We used silicon carbide, which is a very promising candidate material for neuroprosthetics, as our test materials. Not only have we confirmed the outstanding in-vitro response of 3C-SiC and amorphous SiC, we do this in strict
compliance to ISO 10993 thus showing that it is indeed possible to quantitatively assess the performed of materials in a statistically significant and highly repeatable fashion.
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von, Heideman Anne. « Exploring Cancer Drugs In Vitro and In Vivo : With Special Reference to Chemosensitivity Testing and Early Clinical Development ». Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-151826.
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The aims of this thesis were to investigate the utility of in vitro drug sensitivity testing to optimize the use of cancer chemotherapy and to assess the properties of a new cancer drug in a phase I clinical trial. Tumour cells from patients were analysed with the short-term Fluorometric Microculture Cytotoxicity Assay (FMCA). In samples from a wide spectrum of tumour types, the effect of the drug combination FEC (5Fu-epirubicin-cyclophosphamide) was generally appropriately predicted from the effect of the best component drug. However, of samples intermediately sensitive to the best single drug, 45% converted to sensitive when testing the combination. Thus, combination testing may identify advantageous interactions and improve in vitro test performance. In tumour samples from peritoneal carcinomatosis, significant differences in drug sensitivity between diagnoses were observed, cross-resistance between most drugs was modest or absent, and the concentration-effect relationships for two drugs in individual samples varied considerably. Thus, for optimal selection of drugs for intraperitoneal chemotherapy, differences in drug sensitivity at the diagnosis and individual patient level should be considered. In samples from patients with ovarian carcinoma, drug sensitivity was related to tumour grade, histologic subtype and patient treatment status. In a homogeneous subset of patients, the FMCA predicted individual patient tumour response with high sensitivity and specificity. Thus, if carefully interpreted in the context of important clinical variables, in vitro testing could be of value for individualizing chemotherapy in ovarian cancer. Employing a once weekly dosing schedule in a phase I trial, the mechanistically new and preclinically promising NAD depleting drug CHS 828 produced dose limiting thrombocytopenia and gastrointestinal toxicity without clear evidence of anti-tumour efficacy. It is concluded that in vitro drug sensitivity testing could be a way to optimize the use of chemotherapy and that successful development of new cancer drugs needs improved strategies.
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Gajendran, Jayachandar [Verfasser]. « Performance testing of medicated chewing gums with the goal of establishing in vitro in vivo correlation / Jayachandar Gajendran ». Mainz : Universitätsbibliothek Mainz, 2017. http://d-nb.info/1123986231/34.
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Masango, Mxolisi Goodwill. « A comparative analysis of the cytotoxicity of cyanotoxins using in vitro (cell culture) and in vivo (mouse) assays ». Diss., Pretoria : [s.n.], 2007. http://upetd.up.ac.za/thesis/available/etd-05122008-100402/.
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Jay, Naomi (aka Jatovsky). « In vitro and in vivo testing of a traditional Chinese medicine treatment for anal high grade squamous intraepithelial lesions ». Diss., Search in ProQuest Dissertations & ; Theses. UC Only, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3261246.
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Leamy, Patrick J. « Preparation, characterization, and in vitro testing of poly (lactide-co-glycolide) and dextran magnetic microspheres for in vivo applications ». [Gainesville, Fla.] : University of Florida, 2003. http://purl.fcla.edu/fcla/etd/UFE0000729.
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Jones, Rebecca Amy. « Testing the in vivo role of actin cytoskeleton regulators on immune cell behaviour by live imaging studies in Zebrafish larvae ». Thesis, University of Bristol, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.617798.
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Our immune system protects us from infection and abnormal cell growth. But what happens when the function of immune cells is perturbed by the absence of key cytoskeletal regulators? In the immunodeficiency disorder, Wiskott-Aldrich syndrome, patients express dysfunctional variants of WASp, a haematopoietically restricted regulator of the actin cytoskeleton. The disease manifests in recurrent bacterial infections, thrombocytopenia and a severely defective inflammatory response. In this thesis I have utilised a TILLed zebrafish WASp mutant to characterise the effect of WASp knockout on innate immune cell function using a number of assays and live imaging techniques in transparent larvae. I observe defective neutrophil and macrophage migration to a fin wound in the WASp mutant, and increased larval death from systemic bacterial infection as a result of defective phagocytosis and clearance. I have gone on to use the WASp mutant as a null background to screen an allelic range of human WASp patient mutant genes expressed specifically in neutrophils. I show that expression of wild-type hWASp protein can rescue the neutrophil recruitment defect in WASp mutant larvae. Likewise, expression of two point mutants reveals that Cdc42 binding is not essential for hWASp rescue capability, whereas tyrosine phosphorylation of the protein is required. Moreover, expression of a constitutively active hWASp mutant results in larval neutropenia, that mirrors the WASp-related disorder, X-linked neutropenia. Alongside my WASp mutant study, I have also characterised the role of zebrafish Myosin IXb, a haematopoietically restricted atypical RhoGAP, through use of targeted morpholino. I observe decreased neutrophil recruitment to a fin wound in Myosin IXb morphant larvae, whilst live imaging studies demonstrate a contracted morphology and failure to form a polarised leading edge in morphant cells. In summary, I report a live imaging zebrafish study to assess the role of two key actin regulators in vivo, and describe the first instance whereby an allelic range of human mutations are tested in zebrafish to gain a unique insight into immunodeficiency disorders at both a cellular and whole organism level.
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Pawlisz, Andrew V. « Internal residues of the narcotic organic chemicals in the Cladoceran, Daphnia magna ». Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=69519.
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The current work determined whether there is a constant tissue residue associated with narcotic compounds. In this investigation, the cladoceran, Daphnia magna was exposed to lethal levels (48h LC50) of ten, $ sp{14}$C-labelled, narcotic organic chemicals in a closed system. Exposure times, ambient concentrations, and body sizes were varied to evaluate their effects. The $ sp{14}$C-method developed in current work can detect chemicals in single D. magna in concentrations ranging from 0.02 to 6310 mmol/kg. Moreover, the technique detected phobic and lipophilic chemicals equally well. The technique's sensitivity (nmol/kg) allowed for detection of differences in the internal concentrations of pollutants among the unaffected, immobilized, and dead D. magna. Immobilized D. magna contained between 0.14 mmol/kg and 200 mmol/kg of narcotics. On the average, however, the internal residues were 3.1 mmol/kg (95%CL = 3.1 $ pm$ 2.0). This agreed with literature values. The effects of time of exposure, ambient concentration, and body size on the tissue residues of narcotics varied with the chemical compound.
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Rais, Bushra [Verfasser], et Peter P. [Akademischer Betreuer] Müller. « In vivo imaging models for testing the inflammatory potential of implant materials and infection / Bushra Rais ; Betreuer : Peter P. Müller ». Braunschweig : Technische Universität Braunschweig, 2015. http://d-nb.info/1175819549/34.
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Sega, Estela Munhoz. « Determinação da toxicidade in vitro e in vivo de novos organofosforados e ressonancia magnetica nuclear do cloreto de acetilcolina ». [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311381.
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Orientadores: Nelci Fenalti Hoerhr, Roberto Rittner NetoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Esse estudo analisou as propriedades toxicológicas de novos compostos organofosforados. Foram realizados experimentos para avaliar a atividade anticolinesterásica desses organofosforados, in vitro, no sangue total através do método de Ellman modificado. Para determinar a sua citotoxicidade foram utilizadas células PC 12, com as quais avaliamos a viabilidade celular após contato com os organofosforados e determinamos a IC 50, encontrando valores muito diferentes para os diversos organofosforados estudados. Estudos de toxicidade aguda in vivo foram realizados com camundongos, através da metodologia recomendada pela OECD nos quais determinamos a DL50 para três dos organofosforados estudados, sendo que um apresentou toxidade moderada. Foram analisados os efeitos dos solventes nas constantes de acoplamento JHH, JHH, JNC e 2Jnc em espectros de RMN de LH e 13C do cloreto de acetilcolina. Os valores das constantes de acoplamento em solventes de diferentes constantes dielétricas (s) não sofreram variações, indicando uma ausência de efeitos de solvente no equilíbrio conformacional do cloreto de acetilcolina (ACh). As constantes de acoplamento mostram que o sistema OCH2CH2N+ tem uma conformação gaúche (sinclinal). O Jnh e Jkc são observados na maioria dos solventes, mas não em solventes clorados e não são dependentes da viscosidade do solvente, esse comportamento foi explicado usando dados de medidas de Ti. Os valores dos coeficientes de difusão de RMN mostraram que a ACh tem uma grande tendência de se agregar quando dissolvida em solventes clorados, fato que pode explicar as diferenças observadas em valores de T1 para o 14N
Abstract: This study analyzed the properties of the news organophosphorus. Experiments had been carried through to evaluate the inhibition of acetylcholinesterase of these organophosphorus, in vitro, through the modified EUman's method. In order to determine its cytotoxicity cells PC 12 had been used, with which we evaluate the cellular viability after contact with the organophosphorus and determined the IC50, different values were found for the diverse organophosphorus. Studies of acute toxicity had been carried through with mice, following the methodology recommended by the OECD in which determine the DL50 for three of the organophosphorus studied, being that one presented moderate toxicity. Coupling constants values ( Jhh and Jnc) obtained from the 'H and 13 C NMR spectra of acetylcholine chloride (ACh) in several solvents with a wide range of dielectric constants (e) are remarkably invariant, indicating an absence of solvent effects in the conformational equilibrium of this compound. Those values show that the OCH2CH2N+ system occurs in a synclinal conformation. The Jnh and Jnc are observable in most solvents, but not in chlorine-containing solvents and are not dependent on solvent viscosity. This behavior was explained using data from Ti measurements. The measurement of NMR diffusion coefficients show that ACh has a greater tendency to aggregate when dissolved in chlorinated solvents, a fact that could explain the observed differences in 14N T1
Mestrado
Patologia Clinica
Mestre em Ciências Médicas
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Delvadia, Poonam. « A NOVEL BIORELEVANT IN VITRO SYSTEM TO PREDICT THE IN VIVO PERFORMANCE OF ORAL TRANSMUCOSAL PRODUCTS ». VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3173.
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In vitro dissolution, release and permeation testing is a common practice during drug product research and development. These in vitro tests, if predictive, are referred to as biorelevant tests and can play diverse roles to facilitate and expedite product development in a cost effective manner. Oral transmucosal products (OTPs) are currently tested using compendial and modified in vitro tests which may or may not be good predictors of in vivo performance due to a lack of biorelevance. A critical need for a broadly applicable and biorelevant in vitro system for OTPs has been expressed in the literature and the goal of this research was the development and validation of a biorelevant in vitro method that can facilitate accurate prediction of the in vivo behavior of OTPs. A combined strategy of appropriate apparatus design and relevant physiological and in vitro variable adjustment was investigated to incorporate biorelevance into evaluation of OTPs. A novel in vitro device, the bidirectional transmucosal apparatus (BTA), was designed and fabricated which allowed simulation of the oral cavity and its physiological variables to evaluate OTPs in a more realistic fashion. The BTA was tested using snus (a type of smokeless tobacco) as the OTP product. A simple and selective high performance liquid chromatographic (HPLC) method with photodiode array (PDA) detection was developed and validated to assess in vitro nicotine release and permeation (Linearity: 0.5 – 32 μg/mL; calibration curve accuracy (%recovery, n=5 ): 97.98-103.20%; calibration curve precision (%RSD, n=5): 0.15-3.14%). The performance of BTA was compared with the modified USP IV flow through apparatus (USP IV) and a commercially available vertical diffusion cell (VDC). The observed in vitro in vivo relationship (IVIVR) slopes with the USP IV, VDC and BTA were 0.27, 2.01 and 2.11 respectively. The BTA was selected over the VDC and USP IV devices because of better simulation and adjustment of variables to incorporate biorelevance in the test of OTPs. Additionally, the BTA allows study of permeation and release simultaneously unlike VDC and USP IV apparatuses. Further, the different BTA parameters were sequentially screened for their impact on in vitro rate of nicotine permeation that can be employed for the optimization of IVIVR for snus. Based on the results, stimulated saliva swallowing rate (SSSR) and media temperature were considered as significant factors affecting in vitro permeation of nicotine and used to further optimize IVIVR for snus. A 32 multifactorial experimental design integrating SSSR (0.32, 1.66 and 3 mL/min) and media temperature (25, 37 and 45 °C) was employed. Based on the response surface analysis, 0.55 mL/min SSSR and 43 °C media temperature were identified as optimal BTA conditions that would give perfect IVIVR (i.e. IVIVR slope close to one) for snus. The experimental value of IVIVR slope (0.92) at these optimal conditions indicated that the BTA is a valid in vitro system for evaluation of OTPs in a biorelevant manner. The applicability of BTA for predicting nicotine permeation from ‘Stonewall’, a dissolvable compressed tobacco was also evaluated. However, comparable in vitro nicotine permeation and in vivo nicotine absorption profiles were not obtained (ratio of in vitro permeation to in vivo absorption rate ranged from 0.04 to 0.14 at different in vitro conditions) either due to the unavailability of reliable clinical data or due to inherently different in vivo behavior of Stonewall compared to snus that would require further modification in the BTA. In conclusion, this research demonstrated the potential of the novel in vitro device to be a valuable tool for the prediction of in vivo performance of snus. The application of the novel bidirectional transmucosal apparatus for other types of OTPs will be an interesting subject for further investigation.
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Freire, Ribeiro da Fonseca Carla Sofia. « Mesenchymal stromal cell therapy for carti-lage regeneration : in vivo testing in a refined preclinical sheep model of chondral and os-teochondral lesions ». Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/289638.
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Una de las patologías musculo-esqueléticas más prevalentes envuelve a las articulaciones y incluye la lesión del cartílago articular, siendo la rodilla una de las articulaciones más afectadas.
Las lesiones del cartílago pueden ser divididas en dos tipos distintos: lesiones de espesor parcial (lesiones condrales) que no penetran el hueso subcondral adyacente, y lesiones de espesor total (lesiones osteocondrales) que penetran el hueso subcondral.
En la actualidad no existe un tratamiento efectivo para las lesiones condrales u osteocondrales, a pesar de existir un gran esfuerzo de investigación en este sentido. La tendencia actual es desarrollar nuevos métodos celulares y basados en ingeniería tisular que puedan solucionar las limitaciones de las tecnologías existentes. Para este propósito, el uso de modelos animales es de extrema importancia, porque funcionan como una fuente de información única entre los estudios in vitro y la aplicación de la terapia en humanos.
Diversos modelos animales son utilizados en el análisis de estrategias de reparación del cartílago, de pequeños a grandes animales. Los pequeños animales (roedores y conejos) están recomendados para estudios de mecanismo o prueba de concepto cuando datos sobre toxicidad, formulación, respuesta a dosis o seguridad son necesarios antes de otros estudios. No obstante, los grandes animales (perro, cerdo, cabra, oveja o caballo) son necesarios para una verdadera investigación traslacional cuyo objetivo sea obtener aprobación reguladora para el uso clínico en humanos.
Este trabajo presenta el estudio de un modelo experimental animal para la evaluación de una abordaje de terapia celular en la regeneración del cartílago articular de la rodilla. El objetivo fue el desarrollo de un modelo animal refinado, para evaluar la eficacia y seguridad de terapias celulares utilizando células mesenquimales estromales con posible futura aplicación en la medicina humana, y establecer las bases para los ensayos clínicos.One of the widest spread musculoskeletal diseases concerns the joints and involves the lesion of articular cartilage, being the knee one of the most affected joints. Cartilage lesions can be divided on two different types: partial-thickness cartilage lesions (chondral lesions) which do not penetrate the underlying subchondral bone, and full-thickness cartilage lesions (osteochondral lesions) which penentrates the subchondral bone. Actually there is no effective treatment for the chondral or osteochondral lesions, although a large investigation effort is being made in this issue. The present tendency is to develop new cell- and tissue-engineering-based methods that may overcome the size limitations of current technologies. For this purpose, the use of animal experimental models is of extreme importance, because they are a reliable source of information between the in vitro assays and the human therapy application. Several animal models are used for cartilage repair strategies testing, from small to large animal models. Small animal models (rodents or rabbits) are recommended for mechanism or proof of principle studies when data regarding toxicity, formulation, dose response or safety are needed before further pivotal studies. However large animal models (dog, pig, goat, sheep or horses) are necessary for truly translational research aimed at gaining regulatory approval for clinical use in humans. This work presents the study of an animal experimental model for the evaluation of the knee’s cartilage regeneration with cellular therapies approach. The aim was the development of a refined animal model to assess the efficacy and safety of mesenchymal stromal cellular therapies with a possible future application in human medicine, and settle the basis for the clinical trials.
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Iyer, Sunil S. « A 'Biorelevant' Approach for Accelerated In Vitro Release and In Vitro-In Vivo Relationship of a Biodegradable, Naltrexone Implant ». VCU Scholars Compass, 2006. http://hdl.handle.net/10156/1523.
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Gonzalez, Jean. « Development and Testing of a Second Generation Hand-held Optical Imager ». FIU Digital Commons, 2012. http://digitalcommons.fiu.edu/etd/596.
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Hand-held optical imagers are developed towards clinical breast cancer imaging. Herein, a Gen-2 hand-held optical imager has been developed with unique features: (i) image curved breast tissues with ~86% surface contact, and (ii) perform reflectance and transillumination imaging using the novel forked probe heads. Extensive phantom studies were performed using 1% Liposyn solution (background, ~ 300 ml and 1000 ml volumes) and 0.45 cc India Ink (absorption) targets, under different target:background contrast ratios and target depths. Two-dimensional surface images detected target(s) up to 2.5 cm deep via reflectance imaging, and up to 5 cm deep via transillumination imaging. Preliminary studies on gel-based breast phantoms (~700 ml) detected targets via reflectance and transillumination imaging. Preliminary in-vivo reflectance studies on normal and cancerous breast tissues also detected targets, although with artifacts. In future, the portable Gen-2 imager has potential for clinical breast imaging via reflectance and transillumination approach after extensive in-vivo studies.
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Cowder, Justin Dennis. « Testing and application of a novel hybrid combination of ultrasound and motion analysis for estimation of Achilles tendon moment arms in vivo ». Access to citation, abstract and download form provided by ProQuest Information and Learning Company ; downloadable PDF file, 97 p, 2008. http://proquest.umi.com/pqdweb?did=1597632581&sid=4&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Kendrick, Mandy D. « Investigation of ethylene signal transduction mechanisms characterizing the novel gene (AWE1) and testing hypothesis of raf-like CTR1's function in vivo / ». College Park, Md. : University of Maryland, 2009. http://hdl.handle.net/1903/9381.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2009.Thesis research directed by: Dept. of Cell Biology and Molecular Genetics. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Low, Adrian Kah Wai Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. « The molecular biology of cancellous bone defects and oestrogen deficiency fractures, in rodents ; and the in vivo effects of acid on bone healing ». Publisher:University of New South Wales. Clinical School - Prince of Wales Hospital, 2008. http://handle.unsw.edu.au/1959.4/42884.
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The management of significant bone defects, delayed and non-union of fractures can be extremely challenging. Development of specific treatment is hindered by an absence of information regarding the molecular events which regulate these processes. In this thesis, a bilateral cancellous bone defect model of the femur and tibia was developed in a rodent and the spatiotemporal profile of TGF-β, BMP 2 and 7, Smads 1, 4 and 5 characterised. Next, the capability of acid solution to augment healing was tested in both a bone defect and in a closed femoral fracture model. Finally, a long term oestrogen deficiency (OVX) rat model of postmenopausal osteoporosis was characterised and the spatiotemporal profiles of IGF-1, IGFR-1, MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, BMP-2, BMP-4, BMP-7, TGF-β, Smad4, Smad7, VEGF, Flt-1, Ihh and FGF-2 were compared in femoral osteotomies between OVX and Sham groups. The bilateral cancellous defect model was successfully created with a number of advantages with which to recommend its use in future studies. TGF-β, BMP 2 and 7, Smads 1, 4 and 5 had characteristic spatiotemporal profiles during cancellous bone defect healing suggesting that they have a regulatory role. The results of the acid study were inconclusive and problems with substance delivery and maintenance at the desired site need to be addressed in the future to fully test this hypothesis. No significant differences were detected on histology or three-point mechanical testing between the fracture calluses of acid and control groups. In the final study, OVX rats after six months had significantly increased weight and decreased bone mineral density compared to their sham counterparts. A histological delay in osteotomy healing was observed in the OVX group but no significant differences on tensile testing were seen between OVX and Sham groups up to six weeks. Immunohistochemistry revealed that delayed healing may be due to the down-regulation of IGF-1, BMP-2, 4, and 7 and the up-regulation of MMP-3 in OVX compared to Sham groups. In conclusion, the results of this thesis give some insight into the molecular biology of bone defects and osteoporotic fractures. This information may also be useful in the development of specific treatments aimed at augmenting healing in bone defects and osteoporotic fractures.
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Dalmonico, Gisele Maria Leite. « Elaboração e caracterização de biomateriais granulados microporosos de fosfatos de cálcio : teste in vivo em ovinos ». Universidade do Estado de Santa Catarina, 2015. http://tede.udesc.br/handle/handle/627.
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Treatments for bone loss are research topics and involve different areas of scientific knowledge, engineering, physics, chemistry, biology and biomedicine. The biomaterials that stand out as replacement in bone structure treatments are hydroxyapatite, β and α calcium phosphate, biphasic hydroxyapatite/calcium phosphate β and α and hydroxyapatite matrix nanocomposite biomaterials. These biomaterials stand out as bone substitutes because they present a crystallography similar to that of human skeleton bone apatite, being bioactive and biocompatible. Nanostructured biphasic bioceramics are researched and show potential to be bone substitutes in surgical repairing procedures and reconstruction of bone tissue. This project was developed based on research of biomaterials of calcium phosphates, involving the synthesis of two matrices of calcium phosphates: β-calcium phosphate (β-TCP) and hydroxyapatite (HA) and the preparation of microporous granular biomaterials of β-TCP, HA and biphasic compositions HA/β-TCP. All biomaterials were characterized by different techniques: X-ray diffraction, infrared spectroscopy in Fourier transform (FTIR), Raman spectroscopy, specific surface area for BET, particle size by laser diffraction, density of helium pictometria, porosimetry mercury and hydrostatic porosity by Arthur, differential scanning calorimetry, dilatometry, scanning electron microscopy, atomic force microscopy, confocal microscopy, optical microscopy, polarized light microscopy. The interest of this research was to evaluate the performance of biomaterials in in vivo tests for the time periods of 90 and 180 days, in relation to osseointegration and the formation of neoformed bone tissue and determine which biomaterials presented potential as bone replacement for biomedical applications. The results found are encouraging and demonstrate that the granulated microporous biomaterials of calcium phosphate proves to be ability to repair and bone reconstruction for the two test times in vivo evaluated, revealing the osseointegration and bone formation similar between the compositions.
Os tratamentos de perdas ósseas são temas de pesquisa que envolve diferentes áreas do conhecimento científico, engenharia, física, química, biologia e biomédica. Os biomateriais que se destacam como substitutos em tratamentos da estrutura óssea são a hidroxiapatita, os fosfatos de cálcio-β e α, os bifásicos hidroxiapatita/fosfato de cálcio-β, α e os biomateriais nanocompósitos de matriz hidroxiapatita. O destaque destes biomateriais como substitutos ósseos, se deve, por apresentarem cristalografia similar à da apatita óssea do esqueleto humano, por serem bioativos e biocompatíveis. As biocerâmicas bifásicas nanoestruturadas são pesquisadas e demonstram ser promissoras como substitutos ósseos em procedimentos cirúrgicos de reparação e reconstrução do tecido ósseo. Este projeto se desenvolveu com base na investigação de biomateriais de fosfatos de cálcio, envolvendo a síntese de duas matrizes de fosfatos de cálcio: Fosfato de cálcio-β (TCP-β) e hidroxiapatita (HA) e elaboração de biomateriais granulados microporosos de TCP-β, HA e bifásicos HA/TCP-β. Todos os biomateriais granulados foram caracterizados por diferentes técnicas: difratometria de raios X, espectroscopia de infravermelho por transformada de Fourier (FTIR), espectroscopia Raman, área superficial específica por BET, tamanho de partícula por difração a laser, densidade por pictometria de hélio, porosimetria de mercúrio e hidrostática com método de Arthur. Com relação ao comportamento térmico utilizou-se a calorimetria exploratória diferencial, dilatometria. A caracterização microestrutural foi realizada com a microscopia eletrônica de varredura, microscopia de força atômica, microscopia confocal, microscopia óptica, microscopia de luz polarizada. Esse projeto de pesquisa envolveu a elaboração de biomateriais granulados microporosos de fosfatos de cálcio, o interesse foi avaliar o desempenho destes em teste in vivo, para os tempos de 90 e 180 dias em tíbia de ovinos, em relação ao desempenho dos mesmos sobre a osseointegração e a neoformação do novo tecido ósseo. Os resultados encontrados são animadores e demonstram que todas as composições de biomateriais granulados microporos de fosfatos de cálcio, demonstraram capacidade de reparação e reconstrução óssea para os dois tempos de teste in vivo avaliados, revelando a osseointegração e a neoformação óssea semelhante entre as composições.
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Dobbs, Michael G. « Development of a three-trophic level toxicity test utilizing an alga (Chlorella vulgaris), rotifer (Brachinous calyciflorus), and fish (Pimephales promelas) ». Diss., Virginia Tech, 1994. http://hdl.handle.net/10919/40164.
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In this research a test system was developed that is designed as a tool to evaluate the potential hazard of chemicals to aquatic ecosystems. The system developed is a linear three-trophic level food chain consisting of an alga (Ch/ore/la vulgaris), rotifer (Brachionus calyciflorus), and fish (Pimephales promelas). The chemostat design used for the lower two trophic levels was crucial in being able to supply the top trophic level with sufficient food on a continuous basis. The system was initially evaluated using copper (Cu) and selenium (Se) as toxicants. In the copper experiments, results of a 7 day threetrophic level toxicity test were compared with a series of single species tests. The LOEC was 31.5 μg/L based on a temporary impairment of the algal population growth, with a corresponding NOEC of 16.2 μg/L. The algal population at all initially impaired treatment levels demonstrated recovery to control levels by the end of the test. Single species tests with the same species showed impairment at treatment concentrations lower than the corresponding value from the three-trophic level test. The difference in sensitivity is attributable to the fact that most of the Cu in the single species tests was in the dissolved form (approximately 80 %), whereas in the trophic level test most of the Cu was not ( < 15 % dissolved Cu). The three-trophic level Se experiment lasted for 25 days, with both short-term and long-term impacts evident. At the algal trophic level, growth was not impaired on a daily basis at any of the exposure levels (110.3, 207.7, and 396.1 pg/L Se). However, algal densities were slightly reduced at the 207. 7 and 396.1 pg Sell treatments, although not significantly different when the data was pooled across days. Rotifer populations were impaired at these same levels by day 4, and succumbed to the Se by day 7. Fathead minnow growth was also impaired at these two concentrations by day 7. In addition, sub lethal impairment of rotifer and fish growth was evident at the 110.3 pg/L level after day 20 indicating a more subtle trophic impact. Bioconcentration factors ranged between 100 and 1000 pg/L and were found to be dependent on the species, treatment, and day.Ph. D.
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Hofsäss, Martin Andy [Verfasser], Jennifer [Akademischer Betreuer] Dressman, Jennifer [Gutachter] Dressman et Werner [Gutachter] Weitschies. « In vitro release testing as an alternative to establishing bioequivalence of drug products in vivo / Martin Andy Hofsäss ; Gutachter : Jennifer Dressman, Werner Weitschies ; Betreuer : Jennifer Dressman ». Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2021. http://d-nb.info/1229989269/34.
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Ignat, Dana Mihaela. « Characterisation of hepatocellular carcinoma development in a TIF1 alphaL2/L2/CRE-ALB mutant mouse model by in-vivo imaging techniques and its application for pharmacological testing ». Strasbourg, 2009. http://www.theses.fr/2009STRA6087.
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Le carcinome hépatocellulaire (CHC) est la 3ème cause de décès par cancer, avec une survie à 5 ans inférieure à 7%, en raison d’une forte résistance aux chimiothérapies conventionnelles. Le développement de nouveaux traitements représente un enjeu majeur et leur validation préclinique nécessite l’établissement de modèles animaux. Il en est ainsi de la découverte récente du développement spontané de CHC par invalidation du répresseur transcriptionnel TIF1alpha. Deux méthodes innovantes de diagnostic et de suivi en ligne des CHC ont été mises au point: la scannographie haute résolution aux rayons X (microscanner) et la microscopie confocale de fluorescence par fibre optique (FCFM). Un protocole d’injection des produits de contraste FenestraTM a été adapté pour la souris (10 µl/g ip de LC 6 h avant imagerie et 10 µl/g iv de VC 30 mn avant imagerie). Les aspects au microscanner des CHC sont décrits. Le diagnostic des CHC atteint 87% en sensibilité et 77% en spécificité. L’utilisation de la FCFM avec un produit de contraste fluorescent (ProSenseTM 2 nmol/souris), a permis pour la première fois d’observer en temps réel et de manière minimale invasive les aspects histologiques des CHC et un diagnostic in vivo avec 100% de sensibilité et 90% de spécificité. Enfin, un nouvel agent antiangiogénique a été évalué sur la souris mutante TIF1alpha. Malgré une amélioration de 2 mois de la survie actuelle, l’emploi des nouvelles techniques a montré une accélération de la croissance tumorale en début de traitement, ainsi que des altérations minimes au niveau du transcriptome. Ces résultats paradoxaux amènent à s’interroger sur les possibles effets secondaires du traitement testéHepatocellular carcinoma (HCC) is a very poor prognostic cancer resistant to conventional chemotherapy. There is therefore an urgent need for new treatment options and small animal models are the only available means of testing them. The recent discovery that mice lacking TIF1alpha gene spontaneously develop liver tumors, lead us to adapt this HCC model for pharmacological testing. Two original methods of diagnosis and on-line follow up were described: microcomputed tomography scanning (microCT scan) and fiberoptic confocal fluorescence microscopy (FCFM). An appropriate protocol of FenestraTM contrast agent use in mice was described : LC 10 µl/g ip. 6 h before imaging and VC 10 µl/g iv. 30 min before imaging. Together with description of various aspects of liver tumors in microCT scan imaging, this allowed HCC diagnosis with 87% sensitivity and 77% specificity. FCFM imaging employed with a fluorescent marker (ProSenseTM 2 nmol/mouse) allowed for the first time the minimally invasive, real-time, in vivo histological diagnosis of HCC, with 100% sensitivity and 90% specificity. The TIF1 alpha mouse model was subsequently subjected to pharmacological testing with a new antiangiogenic agent. The treated mice survived 2 months longer than the control group. However, using the newly described technique of monitoring, an acceleration of tumor growth was noted in the treatment group after starting treatment. This highlights the benefit of this new approach in providing valuable supplementary information. Minute modifications in molecular profile of treated livers suggested a possible secondary effect of the new compound
Carcinomul hepatocelular (CHC) constituie cea de-a treia cauză de deces prin cancer din lume, cu o supravieţuire la 5 ani mai mică de 7%, datorită rezistenţei importante la chimio şi radioterapia convenţională. Astfel, stabilirea de modele animale de CHC este necesară pentru înţelegerea mecanismelor hepatocarcinogenezei şi pentru validarea în fază preclinică a noilor terapii. Este cazul descoperirii recente a fenomenului de hepatocarcinogeneză spontană în urma invalidării genetice a factorului de transcripţie TIF1alpha la şoarecele de laborator. Optimizarea acestui model s-a realizat prin practicarea unei hepatectomii parţiale, care a dus la apariţia mai precoce a tumorilor hepatice. Pe parcursul acestei teze de doctorat, am pus la punct două metode inovante de diagnostic si monitoraj în timp real al dezvoltării tumorilor hepatice la animalul de laborator: microcomputer tomografia de înaltă rezoluţie (microCT) şi microscopia confocală de fluorescenţă prin fibră optică (FCFM). Pentru a depaşi toxicitatea produselor de contrast specifice microCT-ului, am pus la punct un protocol de injectare adaptat pentru şoarecele de laborator (FenestraTM LC 10 µl/g ip. 4-8 h înaintea microCT şi FenestraTM VC 10 µl/g iv. 15-30 mn înaintea microCT). Aceasta mi-a permis descrierea diverselor aspecte ale CHC în imageria prin microCT şi realizarea diagnosticului de CHC cu o sensibilitate şi o specificitate satisfăcătoare (86,7% şi, respectiv, 76,9%). Utilizarea FCFM împreună cu un marker fluorescent specific celulelor tumorale (ProSenseTM), mi-a permis descrierea pentru prima oară a aspectelor histologice ale CHC in-vivo şi în timp real, de manieră minim invazivă. FCFM permite diagnosticul diferenţial între ficatul normal şi diversele tipuri histologice de CHC, cu o bună sensibilitate şi specificitate (100% şi respectiv 90,5%). In fine, am aplicat aceată metodă pentru testarea unui nou compus anti-angiogenic. Eficacitatea acestui produs a fost evaluată prin studiul duratei de supravieţuire, comparată cu rata de creştere tumorală evaluată prin microCT, şi prin analiza modificărilor la nivel molecular. Astfel am putut demonstra, că, în pofida unei ameliorări a supravieţuirii cu două luni, există o accelerare temporară a vitezei de creştere tumorală la începutul tratamentului, şi de asemenea, modificări minime la nivel de transcriptom. Aceste rezultate paradoxale sugerează existenţa de efecte secundare grave ale tratamentului testat
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LETO, BARONE Maria Stefania. « Analysis of a database to predict the result of allergy testing in vivo in patients with chronic nasal symptoms and the development of the software ARSTAT ». Doctoral thesis, Università degli Studi di Palermo, 2014. http://hdl.handle.net/10447/91193.
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Background. This thesis consist of parts(i)Introduction in wich we present the clinical problem of rhinitis;(ii)the methods to evaluate the diagnostic choises;(iii)the rational errors in Allergy,(iv)the experimental part of thesis with wich we developed the software ARTSTAT,wich is the application of the analysis reported.Objective: We studied the ability of the logistic regression model obtained by the evaluaqtion of a database, to detect patients with positive allergy skin prick test(SPT)and patients with negative SPT. The model developed was valitated using the data set obtained from another medical institution. Methods: The analysis was carried out using a database obtained from a questionnaire administered to the patients with nasal symptoms containing personal data, clinical data result of allergy testing (SPT). All variables found to be significantly different between patients with positive and negative SPT(P<0.05),were selected for the logistic regression models and were analyzed with bacward stepwise logistic regression. A second set of patients from another Institution was used to prove the model. Results: e accuracyof the model identifying, over the second set, both patients whose SPT will bepositive and negative was high. The model detect 96 percent of patients with nasal symptoms and positive SPT, and classified 94 percent of those with negative SPT. Conclusion:The data of the thesis have been preliminary to the creation of a softwarewich cuold help the primary care doctors in diagnostic decision making process ( need of allergy testing), in patients complaining of chronic nasal symptoms.
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Post, Hannah [Verfasser], et Jennifer E. [Akademischer Betreuer] Hundt. « Development and testing of a novel ex vivo assay for studying “pathological” wound healing in human skin / Hannah Post ; Akademischer Betreuer : Jennifer E. Hundt ». Lübeck : Zentrale Hochschulbibliothek Lübeck, 2021. http://d-nb.info/1227903251/34.
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Chambers, Andrea Marie. « Stressed and Strung Out : The Development and Testing of an In Vivo Like Bench-top Bioreactor for the Observation of Cells Under Shear Stress ». University of Dayton / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1438218205.
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Roussel, Tangi. « Développements de méthodes de traitement et d’acquisition du signal pour la Spectroscopie de Résonance Magnétique 2D in vivo ». Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10114/document.
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La Spectroscopie de Résonance Magnétique (SRM) constitue un outil non-invasifunique pour l’exploration biochimique du métabolisme des organismes vivants. Cependant,en raison des champs magnétiques couramment utilisés chez l’homme etle petit animal, la SRM in vivo du proton ne permet pas de quantifier précisémentla concentration de tous les métabolites présents dans le cerveau. La SRM à deuxdimensions spectrales (SRM 2D), technique utilisée en routine en chimie, permetde séparer efficacement les signatures spectrales des métabolites facilitant ainsi leuridentification et leur quantification en termes de concentrations. Les travaux réalisésdans le cadre de cette thèse concernent le développement de méthodes d’acquisitionet de quantification de spectres RMN 2D J-résolus in vivo et sont présentéssuivant deux axes majeurs. Le premier axe concerne les travaux relatifs à la SRM2D J-résolue conventionnelle qui ont fait l’objet du développement d’une séquenceJ-PRESS sur un imageur 7 T pour l’acquisition de spectres 2D sur le cerveau de rat.Les données acquises sont traitées avec une méthode d’analyse spectrale développéeet optimisée spécifiquement pour la quantification de données SRM 2D J-résolues,reposant sur une connaissance a priori et un ajustement numérique dans le domainetemporel. Le second axe concerne les travaux relatifs à la réduction de la duréed’acquisition en SRM 2D avec le développement de techniques basées sur le conceptrécent de RMN ultrarapide. Une nouvelle séquence de SRM 2D J-résolue ultrarapidea été développée et validée sur un imageur 7 T et a permis l’acquisition de spectres2D complets avec une durée d’acquisition de l’ordre de la secondeIn vivo proton Magnetic Resonance Spectroscopy (MRS) is a powerful tool for metabolicprofiling because this technique is non-invasive and quantitative. However,conventional localized spectroscopy presents important in vivo metabolic informationthrough overlapped spectral signatures greatly affecting the quantification accuracy.Two-dimensional (2D) MRS, originally developed for analytical chemistry,has great potential to unambiguously distinguish metabolites. Therefore, metabolitequantification is improved allowing accurate estimation of their concentrations. Inthis thesis, the research findings are presented under two main headings. The firstline of research focuses on conventional 2D MRS J-resolved. A J-PRESS sequencewas developed allowing the acquisition of in vivo 2D MRS spectra, which were processedby a dedicated quantification method. Experiments were performed on therat brain using a 7 T imaging system and different sampling strategies were evaluated.The quantification method, specifically developed to handle 2D J-resolved MRSdata quantification in time domain, is based on a strong prior-knowledge. However,2D MRS suffers from long acquisition times due to the collection of numerous incrementsin the indirect dimension. Therefore, the second line of research focuseson the reduction of acquisition time using recently developed methods based on theultrafast NMR concept. A new pulse sequence was designed, allowing 3D localizedultrafast 2D J-resolved spectroscopic acquisition on a 7T small animal imaging system. This breakthrough allows the acquisition of a complete 2D spectrum in a singlescan, resulting in acquisition times of a few seconds
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Hotta, Juliana. « Biocompatibilidade in vivo de material resiliente temporário para base de prótese modificado por antimicrobianos para tratamento da estomatite protética ». Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/25/25146/tde-04052017-181513/.
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Reembasadores resilientes temporários contendo fármacos antifúngicos foram sugeridos como um tratamento adjunto para estomatite protética. No entanto, antes de utilizar clinicamente estes reembasadores modificados em humanos, é importante avaliar a sua biocompatibilidade em modelos animais. Este estudo avaliou a biocompatibilidade in vivo de um reembasador resiliente temporário para base de prótese (Trusoft) modificado por agentes antimicrobianos em suas mínimas concentrações inibitórias (MCIs) para biofilme de Candida albicans. Dispositivos acrílicos intra-orais (DIOs) foram confeccionados individualmente para 60 ratos Wistar. Os ratos foram divididos em 6 grupos (n=5): 3 grupos controle (Negativo: sem DIO; Geral: DIO sem reembasamento; Positivo: DIO reembasado com Trusoft sem fármacos) e 3 grupos experimentais (DIOs reembasados com Trusoft modificados por fármacos em suas respectivas MCIs: 0,032 g de nistatina, 0,064 g de diacetato de clorexidina e 0,128 g de cetoconazol). Os ratos com ou sem os DIOs foram eutanasiados após 7 e 14 dias de avaliação. A análise histopatológica qualitativa foi realizada comparando-se fotomicrografias de secções histológicas, que foram obtidas utilizando um microscópio óptico que abrangeu transversalmente a região intermolares. As alterações morfológicas no epitélio e queratina foram analisadas quantitativamente através da realização de planimetria computadorizada. Os dados quantitativos foram analisados utilizando ANOVA 2-fatores e teste de Tukey (=0,05). A análise quantitativa mostrou que apenas o grupo com DIO contendo cetoconazol diminuiu significativamente a espessura e a área do estrato córneo em comparação com os outros grupos (p<0,05), que não apresentaram diferenças significativas entre si (p>0,05). Estes resultados estiveram de acordo com os obtidos para análise qualitativa. A incorporação de MCIs de nistatina e diacetato de clorexidina no Trusoft não induziram alterações histopatológicas na mucosa palatina de ratos, sugerindo a biocompatibilidade in vivo deste protocolo para o tratamento de estomatite protética.Temporary resilient denture liners containing antifungal drugs have been suggested as an adjunct treatment for denture stomatitis. However, before clinically using these modified liners in humans, it is important to assess their biocompatibility in animal models. This study evaluated the in vivo biocompatibility of a temporary soft denture liner (Trusoft) modified by antimicrobial agents at their minimum inhibitory concentrations (MICs) for biofilm formation by Candida albicans. Methods: Acrylic intraoral devices (IODs) were individually made for 60 Wistar rats. The rats were divided into the following 6 groups (n=5): 3 control groups (Negative: without IOD; General: IOD without relining; Positive: IOD relined with Trusoft without drugs) and 3 experimental groups (IOD relined with Trusoft modified by drugs at MICs: 0.032 g for nystatin, 0.064 g for chlorhexidine diacetate, and 0.128 g for ketoconazole). The rats with or without the IODs were sacrificed after 7 or 14 days of evaluation. Histopathological qualitative analysis was performed by comparing photomicrographs of histological sections, which were obtained using an optical microscope that transversely covered the inter-molar region. Morphological changes in the epithelium and keratin were quantitatively analyzed by performing computerized planimetry. Quantitative data were analyzed using 2-way ANOVA and Tukey\'s test (=0.05). Quantitative analysis showed that only the group with IOD containing ketoconazole significantly decreased the thickness and area of the stratum corneum compared with the other groups (p<0.05), which showed no significant differences between each other (p>0.05). These results were in accordance with those obtained for qualitative analysis. Incorporation of MICs of nystatin and chlorhexidine diacetate in Trusoft did not induce histopathological changes in the palatal mucosa of rats, suggesting the in vivo biocompatibility of this protocol for treating denture stomatitis.
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MELLO, ROBERTA M. de. « Resistência ao choque térmico de carbeto de silício sinterizado via fase líquida ». reponame:Repositório Institucional do IPEN, 2016. http://repositorio.ipen.br:8080/xmlui/handle/123456789/26375.
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Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2016-06-22T11:45:07Z
No. of bitstreams: 0Made available in DSpace on 2016-06-22T11:45:07Z (GMT). No. of bitstreams: 0
Tese (Doutorado em Tecnologia Nuclear)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
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Maas, Jessica Verena. « Das Schaf als Großtiermodell in der Herzchirurgie am Beispiel der in-vivo-Testung eines Linksherzunterstützungssystems (Mikrodiagonalpumpe) ». Gießen : DVG Service, 2007. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=016277480&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Jacob, Eva. « In-vivo-Testung eines neuartigen BMP-2-TCP-Composite ». Giessen VVB Laufersweiler, 2006. http://d-nb.info/100049599X/34.
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Derache, Philippe. « Influence de la reduction des xenobiotiques organo-nitres sur la peroxydation des phospholipides ». Toulouse 3, 1986. http://www.theses.fr/1986TOU30062.
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Introduction aux problemes de la peroxydation radicalaire des lipides, notamment au travers de la toxicite de l'oxygene. Effets des composes organonitres sur cette toxicite (etudes in vivo, in vitro, etudes de la mutagenicite)
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Jacob, Eva [Verfasser]. « In-vivo-Testung eines neuartigen BMP-2-TCP-Composite / Eva Jacob ». Giessen : VVB Laufersweiler, 2006. http://d-nb.info/100049599X/34.
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Heider, Nele [Verfasser], et Hartmut [Akademischer Betreuer] Gerhards. « In vivo Testung von Hyaluronsäuregelen als Glaskörperersatz / Nele Heider ; Betreuer : Hartmut Gerhards ». München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1203067402/34.
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Kane, Amadou. « Intoxication subchronique par l'ochratoxine a, mycotoxine contaminant les aliments : effets nephrotoxiques et genotoxiques ». Strasbourg 1, 1986. http://www.theses.fr/1986STR13126.
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Distribution tissulaire de l'ochratoxine marquee chez le rat et la souris (voie orale). Etude de la nephrotoxicite subchronique de doses faibles chez le rat en suivant dans l'urine et les tubules la variation des activites enzymatiques. Effet sur les enzymes de cellules renales mdck en culture. Etude de la genotoxicite de l'ochratoxine in vivo et in vitro
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Aleahmad, Turadg. « Improving Students’ Study Practices Through the Principled Design of Research Probes ». Research Showcase @ CMU, 2012. http://repository.cmu.edu/dissertations/129.
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A key challenge of the learning sciences is moving research results into practice. Educators on the front lines perceive little value in the outputs of education research and demand more “usable knowledge”. This work explores the potential instead of usable artifacts to translate knowledge into practice, adding scientists as stakeholders in an interaction design process. The contributions are two effective systems, the scientific and contextual principles in their design, and a research model for scientific research through interaction design.
College student study practices are the domain chosen for the development of these methods. Iterative ethnographic fieldwork identified two systems that would be likely to advance both learning in practice and knowledge for applying the employed theories in general. Nudge was designed to improve students’ study time management by regularly emailing students with explicit recommended study activities. It reconceptualizes the syllabus into an interactive guide that fits into modern students' attention streams. Examplify was designed to improve how students learn from worked example problems by modularizing them into steps and scaffolding their metacognitive behaviors though problem-solving and self-explanation prompts. It combines these techniques in a way that is exceedingly easy to author, using existing answer keys and students' self-evaluations.
Nudge and Examplify were evaluated experimentally over a full semester of a lecture-based introductory chemistry course. Nudge messages increased students’ sense of achievement and interacted with students’ existing time management skills to improve exam grades for poorer students. Among students who could choose whether to receive them, 80% did. Students with access to Examplify had higher exam scores (d=0.26), especially on delayed measures of learning (d=0.40). A key design decision in Examplify was not clearly resolvable by existing theory and so was tested experimentally by comparing two variants, one without prompts to solve the steps. The variant without problem solving was less effective (d=0.77) and less used, while usage rates of the variant with problem solving increased over time.
These results support the use of the design methods employed and provide specific empirical recommendations for future designs of these and similar systems for implementing theory in practice.
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Frantsev, Roman. « In-vivo-Testung des „Vascular Disrupting Agents“ DMXAA am Modell für neuroendokrine und Nebennieren-Tumore ». Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-123181.
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