Dissertations / Theses: 'In vivo studies'

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Al-Duaij, Ahmed Yousuf Mohamed. "Studies of cartilage degradation in vivo." Thesis, Queen Mary, University of London, 1985. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1366.

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A new method has been established to study cartilage breakdown in vivo. Cartilage was implanted into air pouches on the backs of mice or rats and loss of proteoglycan measured biochemically. Using the air pouch it was possible to produce various inflammatory environments either immune or non immune and examine the effects of these upon proteoglycan loss. It was found that the various type of inflammation failed to accelerate proteoglycan loss from implanted cartilage. Subsequently a variety of drugs used in the treatment of the arthropathies were examined for their effect on both inflammation and cartilage breakdown. Using xiphisternum a difference could be shown between non-steroidal anti-inflammatory drugs (NSAID) and d-penicillamine in that, NSAID failed to protect the cartilage whereas d-penicillamine prevented proteoglycan loss. This type of cartilage was not examined further, as it was not characteristic of articular cartilage - being surrounded by perichondrium. Later articular cartilage was implanted once again into different inflammatory situations and drug effects evaluated. It was found using this cartilage that all the drug 0 used protected from loss of proteoglycan and whereas some inhibited inflammation (indoniethacin and dexamethasohe), 2a levamisole had no effect in contrast, d-penicillamine potentiated the inflammatory response. Finally the mode of action of the drugs in this method is discussed.

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De, Varennes Benoit. "Ex-vivo canine heart preservation : metabolic studies." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56680.

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The recently developed method of nuclear magnetic resonance spectroscopy allows for continuous monitoring of high energy phosphate compound (ATP and Phosphocreatine) and intracellular pH of tissues or whole organs. In other to better understand why ex-vivo hearts can be preserved for longer periods when perfused with oxygenated crystalloid solutions under hypothermic conditions, two groups of canine hearts were studied with nuclear magnetic resonance spectroscopy.
Group 1 = Canine hearts preserved for 4 hours by immersion into a 4$ sp circ$C saline solution.
Group 2 = Canine hearts preserved for 24 hours by continuous coronary perfusion with a modified oxygenated Krebs solution at 4$ sp circ$C.
The longer preservation of ATP and phosphocreatine, as well as the slower decrease of intracellular pH in Group II hearts are hypothesized to be the reasons why perfused hearts can be preserved for longer periods of time.

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Haggie, P. M. "Spectroscopic studies of labelled proteins in vivo." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599831.

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Although metabolic enzymes and metabolic pathways have been well characterised in vitro, understanding of the control of metabolic processes in vivo is relatively poor. The extrapolation of studies performed on purified proteins into the intact cell is questionable. Consequently, there is a need to study enzymes in vivo, however, there are a limited number of techniques available to study specific proteins in a minimally invasive manner. Reported in this thesis are studies in which techniques are developed to permit specific proteins to be distinguished using nuclear magnetic resonance (NMR) and fluorescence visibility. A method to selectively label proteins by the biosynthetic incorporation of amino acid analogs has been developed in Saccharomyces cerevisiae. This method is non-invasive, and the probes introduced into specific proteins are very small and relatively non-perturbing. Using an inducible expression system, pyruvate kinase 1 and citrate synthase 1 were synthesised in vivo and 5-fluorotryptophan in the growth medium was selectively incorporated into the proteins. This labelling permitted the visualisation of these proteins using non-invasive NMR of whole cells. A complementary optical technique was also developed. This method incorporated a fluorescent amino acid analog (5-hydroxytryptophan) into proteins to allow the study of the proteins using more sensitive fluorescence techniques in whole cells. 5-Hydroxytryptophan was successfully incorporated into phosphoglycerate kinase which permitted visualisation of the protein in whole cells using laser scanning confocal microscopy. For both pyruvate kinase 1 and citrate synthase 1, there was evidence of enzyme immobilisation in whole cells. These investigations present direct evidence for the association of enzymes in vivo. The implications of these results in terms of the organisation of metabolism are discussed. The fluorescence studies have important implications both in terms of studying proteins in vivo with microscopy and fluorimetry and in the development of techniques to fluorescently label proteins.

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Frost, Gwenda. "In vivo NMR studies of Debaryomyces hansenii." Thesis, University of Liverpool, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316609.

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Preece, N. E. "Studies on chemical-induced autoxidation in vivo." Thesis, University of Surrey, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376361.

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Marczinke, Beate Inge. "In vivo studies of viral ribosomal frameshifting." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624918.

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Karunakaran, Chandrapriya. "Role of Cavitation during Bulk ultrasound Ablation: Ex vivo and In vivo Studies." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1343051845.

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8

Carroll, N. J. H. "Studies on adherent and luminal gastric mucus in vivo." Thesis, University of Newcastle Upon Tyne, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378844.

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Pearce, Neil William. "Gallbladder contractility : in vitro and in vivo studies." Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416098.

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Klenerman, Paul. "Immune responses against persistent viruses studies in vivo." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272756.

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Healy, Claire Marie. "Recurrent oral ulceration : in vivo and in vitro studies." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250670.

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Fray, Anne Elizabeth. "In vivo studies of brain metabolism in rat striatum." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308692.

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Fox, G. G. "In vivo NMR studies of intact higher plant systems." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293431.

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Hughes, Nigel P. "In vivo and in vitro studies of biomineralisation processes." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279881.

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Cotter, Matthew James. "In vitro and in vivo studies of murine neutrophils." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274944.

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Ufret-Vincenty, María de L. (María de Lourdes) 1974. "Studies towards the in vivo inhibition of oligosaccharyl transferase." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/30018.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003.
Vita.
Includes bibliographical references.
Protein glycosylation is an important process because of the great diversity of glycoproteins that can be produced by the introduction of different oligosaccharide sequences. Our group has made significant progress in the study of asparagine-linked glycosylation. This process is catalyzed by oligosaccharyl transferase (OT), which is a membrane-associated enzyme found in the lumen of the endoplasmic reticulum (ER). A variety of inhibitors that bind tightly to OT in vitro, with K[sub]i s as low as 10 nM, have been synthesized. The development of peptides capable of inhibiting OT in vivo would be desirable, since there is no bio-available inhibitor that targets N-linked glycosylation directly. Both active and passive strategies for delivering inhibitors into cells were studied. Internalization sequences were attached to the inhibitors to be used as delivery vectors. An ER retrieval sequence was used to target inhibitors to the ER and fluorescent labels were used to trace the inhibitors in the interior of the cell. It was determined that inhibitors with the internalization sequences, both with and without the ER retrieval sequence, were internalized by cells in culture. Also, inhibitors with a BODIPY fluorophore were internalized by cells in culture. Those that contained the C-terminus ER retrieval sequence were concentrated in the ER, while the inhibitors without the ER retrieval sequence were found distributed throughout the cell. Nevertheless, inhibitors with an amide C-terminus were internalized with more ease that those with a free acid at the C-terminus, which were the ones that contained the ER retrieval sequence. Compounds were assayed for in vivo inhibition of OT with a system in which the activity of secreted alkaline phosphatase is related to
(cont.) the glycosylation state of this glycoprotein, since unglycosylated protein is not secreted from the cell. Some of the compounds containing internalization sequences were determined to be in vivo inhibitors of OT, as well as some of the compounds labeled with the BODIPY fluorophore.
by María de L. Ufret-Vincenty.
Ph.D.

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Lobato, José Ventura Macieira de Sousa. "In vivo studies of bone grafts for maxillofacial surgery." Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7165.

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Li, Pui-Kai. "Synthesis, biochemical and in vivo studies of aromatase inhibitors /." The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487588939089401.

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Zsigmond, Peter. "Biochemical and pharmacokinetic studies in vivo in Parkinson’s disease." Doctoral thesis, Linköpings universitet, Neurokirurgi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-91294.

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Parkinson’s disease (PD) is a neurodegenerative disease affecting approximately 25000 people in Sweden. The main cause of the disease is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) projecting to the striatum. The motor symptoms of PD, due to decreased levels of dopamine, includes bradykinesia, rigidity and tremor. During the 1960ies oral L-dopa treatment was introduced increasing quality of life for PD patients. In recent decades, enzyme inhibitors have been introduced, increasing bioavailability of L-dopa in plasma. After 5-10 years of L-dopa treatment, 50% of PD patients develop disabling dyskinesias. This can be due to rapid changes in L-dopa conentrations with non physiological stimulation of the dopamine receptor. For over 20 years deep brain stimulation (DBS) has grown to be a good neurosurgical procedure for improving quality of life in advanced PD with disabling dyskinesias. With stereotactic technique, electrodes are implanted in the brain and connected to a pacemaker sending electrical impulses. The most common target in PD is the subthalamic nucleus (STN). The knowledge about DBS mechanism(s) and its interaction with L-dopa is unsatisfactory. The aims of this thesis were; to study the effect of the enzyme inhibitor entacapone on the L-dopa concentration over the blood brain barrier (BBB); to study possible interactions between L-dopa and DBS; to study alterations in neurotransmitters during DBS; to visualize microdialysis catheters in anatomical targets and to estimate sampling area of the catheters. In all four papers the microdialysis technique was used. It is a well-established technique for continuous sampling of small water-soluble molecules within the extracellular fluid space in vivo, allowing studies of pharmaceutical drugs and neurotransmitters. We showed that entacapone increases the bioavailability of L-dopa in blood with a subsequent increase of L-dopa peak levels in the cerebrospinal fluid. This in turn may cause a larger burden on the dopaminergic neurons causing an increased degeneration rate and worsening of the dyskinesias; we showed that 18% of L-dopa crosses the BBB and that there is a possible interaction between L-dopa and DBS, L-dopa concentrations increase during concomitant STN DBS, which can clarify why its possible to decrease L-dopa medication after DBS surgery. The research has also shown that STN DBS has an effect on various neurotransmitter systems, mainly L-dopa, dopamine and GABA. We showed that STN DBS may have an effect on the SNc, resulting in putaminal dopamine release. We have shown that with stereotactic technique, it is safe to do microdialysis sampling in specific areas in the human brain. Simulations with the finite element method combined with patient specific preoperative MRI and postoperative CT images gave us exact knowledge about the positions of the catheters and that the studied structures were the intended. The research has given an assumption of the maximum tissue volume that can be sampled around the microdialysis catheters.

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Wroblewski, Joanna. "Studies on chondrocyte differentiation in vivo and in vitro." Stockholm : Kongl Carolinska Medico Chirurgiska Institutet, 1987. http://catalog.hathitrust.org/api/volumes/oclc/15730803.html.

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21

Lobato, José Ventura Macieira de Sousa. "In vivo studies of bone grafts for maxillofacial surgery." Tese, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7165.

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22

Berdiñas, Torres Verónica J. "Exposure systems and dosimetry of large-scale in vivo studies /." Zürich : ETH, 2007. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17429.

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Amoasii, Leonela. "In vivo functional studies of myotubularin in mouse skeletal muscle." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ037.

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La Myotubularine (MTM1) est une 3-phosphatase à phosphoinositides (PI) mutée dans la myopathie centronucléaire liée au chromosome X (XLCNM), caractérisée par une faiblesse musculaire et un positionnement anormal des noyaux dans les fibres musculaires. MTM1 définit une grande famille de phosphatases, exprimées dans tous les tissus, et qui englobent des phosphatases catalytiquement actives et inactives. Les myotubularines actives dephosphorylent le phosphatidylinositol 3 monophosphate [PtdIns3P] et le 3,5-bisphosphate [PtdIns(3,5)P2] en PtdIns et PtdIns5P, respectivement. Le rôle de MTM1 et son activité phosphatase à lipide dans le muscle restaient peu connus. L’étude approfondie de la protéine a révélé une association de MTM1 au réticulum sarcoplasmique des triades, un sous-compartiment impliqué dans la régulation calcique. La caractérisation de la souris Mtm1 KO, qui reproduit la XLCNM, a témoigné d’une anomalie de l’organisation et de la forme du réticulum sarcoplasmique. Afin d’explorer l’implicationde l’activité phosphatase de MTM1 dans l’organisation de réticulum sarcoplasmique, j’ai utilisé une approche in vivo avec des virus adéno-associé (AAV) pour moduler l’activité phosphatase en sur-exprimant MTM1 et sa forme phosphatase-inactive (MTM1-C375S) dans un muscle sauvage. L’observation des muscles transduits a dévoilé une implication de MTM1 dans le remodelage du réticulum sarcoplasmique et un rôle potentiel de PtdIns3P avec MTM1 dans la courbure des membranes du réticulum sarcoplasmique. Afin de comprendre l’importance de l’activité phosphatase dans le maintien du phénotype XLCNM, les muscles de souris Mtm1 KO ont été injectés avec ces AAVs contenant la forme active et inactive de MTM1 au moment de l’apparition des premiers signes de XLCNM. Étonnamment, la forme phosphatase-inactive(MTM1-C375S) a sauvé le phénotype de la souris Mtm1 KO de la même façon que la forme active, suggérant que l'activité de phosphatase de MTM1 n’est pas nécessaire pour le maintien de la structure intracellulaire des fibres du muscle adulte. Ces données suggèrent que MTM1 exerce une fonction phosphatase-indépendante dans le maintien de la structure musculaire, certainement via des interactions protéine-protéine, et une fonction phosphatase-dépendente dans le remodelage de la forme du réticulum sarcoplasmique dans le muscle squelettique
Myotubularin (MTM1) is a phosphoinositide (PI) 3-phosphatase mutated in X-linked centronuclear myopathy (XLCNM), a rare congenital myopathy characterized by muscle weakness and abnormal positioning of nuclei in muscle fibers. MTM1 defines a large family of ubiquitously expressed catalytically active and inactive phosphatases. Active myotubularins dephosphorylate both phosphatidylinositol 3-phosphate [PtdIns3P] and 3,5-bisphosphate [PtdIns(3,5)P2] to PtdIns andPtdIns5P, respectively. The specific role of MTM1 and its PI phosphatase activity in muscle remains unknown. Comprehensive analysis of the protein unveiled the association of MTM1 with the sarcoplasmic reticulum (SR) at the triads. Characterization of Mtm1-KO mouse, which reproduce the XLCNM phenotype, revealed a defect of SR organization and shape. In order to gain insight into the involvement of MTM1 phosphatase activity on SR shape and organization, we employed an in vivo approach using Adeno-Associated Virus (AAV) to modulate the phosphatase activity by overexpressingMTM1 and its phosphatase inactive mutant in wild type muscle. The analysis of transduced muscle revealed the involvement of MTM1 in the SR remodeling and its potential role together with PtdIns3P in modulating membrane curvature. In order to understand the importance of the phosphatase activity in the generation of the XLCNM phenotype, Mtm1 KO mice were injected with AAV expressing the active form and the phosphatase inactive form. Surprisingly, both, the phosphatase active and the phosphatase inactive mutant corrected the Mtm1-KO mouse phenotype to a similar extent, thus suggesting that the PI-phosphatase activity of MTM1 is not essential for adult skeletal muscle maintenance. Our data indicates that MTM1 has a phosphatase-independent function in adult muscle structure maintenance and a phosphatase-dependent function in sarcoplasmic reticulum remodeling and shape in skeletal muscle

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Oldfield, Matthew David. "Glycation and tubulointerstitial injury : in vitro and in vivo studies." Thesis, University of Leicester, 2002. http://hdl.handle.net/2381/29406.

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Tubulointerstitial disease is a prominent phenomenon that underlies diabetic nephropathy and correlates closely with declining renal function. The formation of myofibroblasts represents a pivotal process in the development of tubulointerstitial fibrosis. Although the origin of these cells remains unclear, the cytokine transforming growth factor-p (TGF-P) has been shown to mediate the in vitro phenotypic transformation of tubular epithelial cells into myofibroblasts, a process known as transdifferentiation. The pathogenic link between chronic hyperglycaemia and the development of tubulointerstitial injury has not been fully elucidated, however diabetes mellitus is associated with the increased accumulation of a group of heterogeneous protein modifications termed advanced glycation endproducts (AGEs). Interactions between AGEs and specific receptors such as RAGE induce pleiotropic cellular effects including the increased expression of cytokines. This thesis explored the role of AGEs in inducing epithelial to myofibroblast transformation. Specific binding of I AGE-BSA to cell membranes prepared from a rat proximal tubule cell-line, was observed. Binding characteristics, immunoblotting and real time PCR experiments established that this binding site was RAGE. Whole cells exposed to AGEs including a physiological AGE-moiety, carboxymethy-lysine, demonstrated time and dose-dependent epithelial-myofibroblast transdifferentiation as determined by morphological changes and de-novo oc-smooth muscle actin expression. Reciprocal loss of expression of the epithelial antigens E-cadherin and zonula occludens was also seen. The addition of neutralising antibodies to RAGE or to TGF-6 abrogated AGE-mediated effects and prevented an observed AGE-RAGE augmentation of TGF-6 protein production. Furthermore, there was evidence of proximal tubular transdifferentiation in long-term diabetic rats and in a renal biopsy from a patient with type I diabetes. Administration of an AGE cross-link breaker, phenyl-4,5-dimethylthiazloium (ALT 711) reduced AGE accumulation, TGF-6 expression and transdifferentiation in diabetic rats. These studies provide a novel mechanism to explain the development of tubulointerstitial disease manifested in diabetic nephropathy and provide a new treatment target.

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Kantidakis, Theodoros. "In vivo studies of repressors of RNA polymerase III transcription." Thesis, Thesis restricted. Connect to e-thesis to view abstract, 2008. http://theses.gla.ac.uk/161/.

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Thesis (Ph.D.) - University of Glasgow, 2008.
Ph.D. thesis submitted to the Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, 2008. Includes bibliographical references. Print version also available.

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Delve, Robin. "Studies on cytotoxic aldehydes generated during lipid peroxidation in vivo." Thesis, University of Exeter, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317350.

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Galbraith, Sareen Elizabeth. "Comparative studies of morbillivirus infections in vivo and in vitro." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322859.

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Halliday, Jane. "In vivo Â¹Â³C MRS studies of carbohydrate metabolism." Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272732.

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Turner, Sarah Kistler. "In vivo studies of the Kaposi's sarcoma associated herpesvirus (KSHV)." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251596.

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Pippard, D. F. "Studies on rodent endometrial tissue in vitro and in vivo." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234004.

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A system for culturing endometrial cells was developed and used to study the growth curves and morphology of cells from various stages of gestation. The density of cultured cells derived from tissue explanted on days 4 and 5 of pregnancy showed an exponential increase in culture, while the density of cells from tissue explanted on day 10 remained steady and from day 15 declined exponentially. Cells from days 5 and 10 survived for prolonged periods in culture indicating that decidual tissue is not controlled solely by a 'programmed lifespan'. Cells from days 10 and 15 had a similar morphology, while that of cells from day 5 initially differed, but came to resemble cells from the other days over the course of the culture period, indicating that some differentiation occurred in vitro. The distribution of lipid and carbohydrate in the cells was found to alter both over the culture period and with the stage of gestation. The changes loosely reflected the distribution of the substances in decidual tissue in vivo. The effects of progesterone and oestrogen on the morphology of cells from day 4 of pregnancy were examined by scanning electron microscopy. In physiological concentrations, neither steroid had any discernible effect. Studies by other authors have shown the progestrone withdrawal leads to decidual regression but the in vitro results indicate that this is not due to a direct dependence on progesterone. The morphology of the endometrium and stroma during the first 24 hours following oil instillation into the mouse uterus in vivo were followed by light and electron microscopy: epithelial degeneration and stromal decidualization were observed. When indomethacin (an inhibitor of prostaglandin synthesis) was given before, or at various stages after, oil instillation, the rate of epithelial breakdown was decreased and decidualization was inhibited. The combined actions of indomethacin and oil, however, resulted in considerable stromal cell damage.

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BRITTOLI, ALVARO. "“In vitro” and “in vivo” studies on innate immune cells." Doctoral thesis, Università del Piemonte Orientale, 2018. http://hdl.handle.net/11579/97191.

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De, Luca Cristina. "In vivo studies of mitochondrial tRNA mutations in S. cerevisiae." Doctoral thesis, La Sapienza, 2005. http://hdl.handle.net/11573/916860.

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Yeast mitochondria were taken as a versatile tool to investigate the pathogenecity and the mechanism of mitochondrial dysfunction due to point mutations in tRNA genes correlated in humans with neurodegenerative diseases. The biolistic mutants LysG38A, equivalent to the G8328A mutation correlated in humans with mitochondrial encephalomyopathy, and IleT33A, equivalent to the human position 4290 of tRNAIle, were constructed and characterized. The analysis of two other yeast mutants in the anticodon region revealed that mutations involving the same position even on different tRNA genes may cause similar defects. Moreover, the efficiency of the mt-tRNA-synthetases as well as the EF-Tu to suppress the defective phenotype was tested. Finally, the importance of the nuclear background in which the mitochondrial mutation is expressed was investigated by changing the nuclear context of each mutant and quantifying the expression level of the TUF1 gene in different wild-type and/or rho° strains. The results here described may allow the possibility to investigate the pathogenic potential of some tRNA human mutations and to search for nuclear genes that can either suppress or modify the defective phenotype

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MAGLIE, M. DE. "BIODISTRIBUTION AND TOXICITY OF METALLIC NANOPARTICLES:IN VIVO STUDIES IN MICE." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/487404.

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In the last decade, nanotechnology has emerged as one of the fastest growing area of science. This is a highly promising field for the generation of new engineering applications, consumer products, medical healthcare and medicine. However, the increasing development of nanomaterials (NMs) is not supported by in vivo studies taking systematically into consideration nanoparticles (NPs) types, doses and period of treatment that would allow to forecast possible adverse outcomes that might occur upon human exposure. In our studies, fully characterized silver nanoparticles (AgNPs) and iron oxide nanoparticles (IONP), designed for cancer treatment, were used to assess biodistribution and potential toxic effects after single intravenous and repeated oral administration in mice. Unexpected histopathological findings, strictly related to the physicochemical properties, i.e. size and vehicle used for the NPs synthesis, were observed after intravenous administration. This confirms that a complete characterization of NPs is of the most importance for the identification of in vivo outcomes. NPs mainly localized in organs containing large number of specialized tissue-resident macrophages belonging to the mononuclear phagocyte system. The retention of NPs in these tissues raises concerns about the potential toxicity. The 28 days repeated oral administration of AgNPs demonstrated that the brain is the organ where Ag accumulation takes place. In fact, Ag it is still detected in brain after the recovery period because of its low clearance. Morphological changes observed in the blood brain barrier (BBB), and the involvement of glial cells in response to AgNPs administration, suggested a perturbation of brain homeostasis that should be taken into consideration and further investigated.

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Fahy, Patricia A. "Ovarian inhibin : in vitro studies using bovine granulosa cells and in vivo studies in rats." Thesis, University of Reading, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309518.

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Ma, Da, and 马达. "In vivo and ex vivo studies of intraocular tamponade agents and their clinical relevance in intraocular drug delivery." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B4454618X.

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Chan, Richard Muller William J. "In vivo structure-function studies of the ErbB2 receptor tyrosine kinase /." *McMaster only, 2004.

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Lahtinen, Mika. "NO Effect on Inflammatory Reaction in Extracorporeal Circulation : Ex vivo Studies." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5908.

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Nitric oxide (NO) is expressed in inflammatory tissues. However, NO effects are controversial in inflammation; NO is described as acting in a dose dependent manner and possess both pro-inflammatory and anti-inflammatory properties.

The present thesis explored the role of NO in relation to white blood cell (WBC) and protein system activation by foreign surfaces in simulated extracorporeal circulation (SECC) using human whole blood from volunteer donors. Three doses of NO, 40 ppm, 80 ppm and 500 ppm, were administered and an array of markers of WBC and protein activation were studied. Neutrophil degranulation was detected with myeloperoxidase (MPO), human neutrophil lipocalin (HNL) and lactoferrin (LF); eosinophil degranulation with eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO); and basophil degranulation with histamine. Furthermore, whole blood and WBC capacity to produce reactive oxygen species (ROS) were studied and cytokine release was measured with IL-1 and IL-10. Complement activation was measured with C3a and C5b-9 complex and contact system activation with FXIIa-C1INH, FXIIa-AT, FXIa-C1INH and FXIa-AT.

NO increased neutrophil degranulation at all dose levels and 80 ppm NO increased basophil degranulation; whereas, NO exerted no effect on eosinophil degranulation, WBC subset counts, cytokine release or capacity to produce ROS. In addition, while increasing both specific and azurophil degranulation with 40 ppm, 80 ppm and 500 ppm, NO reversed the classical degranulation hierarchy with 500 ppm and azurophil degranulation became predominant. Furthermore, NO effect was greater with 500 ppm than with 80 ppm, indicating a dose response effect. The lack of iNOS mRNA expression in WBC and lack of L-NAME effect on degranulation and nitrite/nitrate production, together with absent increase in nitrite/nitrate in controls, excluded autocrine or paracrine regulation of degranulation. FXIIa-AT and FXIa-AT complexes increased and became predominant during early recirculation, whereas FXIIa-C1INH and FXIa-C1INH complexes were predominant at baseline but remained unaltered, suggesting contact system inhibition predominantly via AT. C3a and C5b-C9 increased. NO had no effect on either contact or complement system activation; however, 500 ppm NO shortened active clotting time.

In conclusion, the present data suggest that NO has a direct effect on neutrophil and basophil degranulation. Recognition of NO as an enhancer of degranulation may give access to new therapeutic tools for local and systemic inflammatory therapies; whereas, the identification of increased AT mediated inhibition of FXIIa and unchanged C1INH complexes presents new possibilities for therapeutic intervention in conditions such as hereditary angioedema and heart surgery.

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Li, Yan, and n/a. "In vitro and in vivo studies on the absorption of mitoquinone." University of Otago. School of Pharmacy, 2007. http://adt.otago.ac.nz./public/adt-NZDU20070615.135534.

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Mitoquinone (MitoQ₁₀ mesylate) is a mitochondria-targeted antioxidant for the treatment of neurodegenerative diseases. As the oral bioavailability of mitoquinone is low in rat, it is necessary to better understand the mechanisms of its absorption in rat and in human. The aims of this thesis were 1) to investigate oral absorption mechanisms of mitoquinone in Caco-2 cell monolayers and in a rat intestinal tissue model; 2) to investigate the correlation between chemical structure and permeability of mitoquinone analogues in Caco-2 cell monolayers; and 3) to explore the hypothesis that active transport and/or drug metabolism contribute to the pharmacokinetics of oral mitoquinone in rat. In Caco-2 studies, transport of mitoquinone was polarized with the apparent permeability (P[app]) from basolateral (BL) to apical (AP) (P[appBL to AP]) being >2.5-fold the P[app] from AP to BL (P[appAP to BL]). The P[appBL to AP] value decreased by 26%, 31% and 61% by P-glycoprotein (P-gp) inhibitors verapamil 100 [mu]M, cyclosporine A (CsA) 10 [mu]M and CsA 30 [mu]M, respectively, whereas the P[appAP to BL] increased 71% by CsA 30 [mu]M. Some of the intracellular mitoquinone was reduced to mitoquinol and subsequently metabolized to glucuronide and sulfate conjugates. Apical effluxes of mitoquinol sulfate and mitoquinol glucuronide conjugates were significantly decreased by cyclosporine A 30 [mu]M and the breast cancer receptor protein (BCRP) inhibitor, reserpine 25 [mu]M, respectively. In the presence of 4% bovine serum albumin on the BL side, the P[appAP to BL] was 4.52 � 0.92 x 10⁶ cm/s. Based on a absorption-disposition model, F[a] value of mitoquinone in human is estimated to be 56%. A bellshaped relationship exists between the Caco-2 permeability of mitoquinone analogues and their lipophilicity. Permeability of mitoquinone analogues initially increases as lipophilicity increase, reaches a maximum, and then decreases due to significant cellular accumulation and active efflux. The physicochemical parameters of mitoquinone and its analogues (such as log P or polar surface area) alone do not predict their permeability across the cell membranes. The bidirectional transport of mitoquinone displays polarity across rat ileal mucosa. The P[app] from s to m (P[app s to m) of mitoquinone decreased and P[app m to s] increased but not significantly by P-gp inhibitor CsA 30 [mu]M. The tissue accumulation of mitoquinone was ~16% of the total amount of mitoquinone added. In addition, several phase I and one phase II metabolites generated by rat ileum tissue were detected. Results from pharmacokinetic studies indicate that mitoquinone was poorly (~24%) but rapidly absorbed and conjugated after oral administration. It was quickly excreted as unchanged drug and as its glucuronides (the major metabolites in rat) into intestine where it was reabsorbed. P-gp inhibition studies in rat indicate that inhibition of P-gp may increase the intestinal absorption of mitoquinone, but cannot change its oral bioavailability due to increased first-pass phase II metabolism and decreased enterohepatic recycling. In conclusion, mitoquinone is poorly absorbed in rat but may be well absorbed in human. The barrier functions of intracellular metabolism and the action of P-gp to oral absorption of mitoquinone in human may be less significant, whereas P-gp play an important role in the absorption and disposition of mitoquinone in rat in vivo. These results, together with those from its analogues, demonstrate that the actual absorption profile of a compound depends on its intrinsic membrane permeability, transporter affinity, metabolizing enzyme affinity and plasma protein binding affinity.

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39

Gustafson, Carl-Johan. "In vitro and in vivo studies on biodegradable matrices for autotransplantation /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-592-5/.

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Quisth, Veronica. "Studies on the regulation of human skeletal muscle lipolysis in vivo /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-167-9/.

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41

Böttiger, Ylva. "Metabolic drug interactions in man : methodological aspects on in vivo studies /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4207-2/.

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42

Walter, Susan Valerie. "In vivo and in vitro studies of cardiocytes in genetic hypertension." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74040.

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43

Martin, Francois-Pierre. "Metabonomic studies of mammalian-microbe and pro-biotic interactions in vivo." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439825.

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44

Corcoran, Jenna Frances. "Effects of pharmaceuticals in fish : in vitro and in vivo studies." Thesis, University of Exeter, 2013. http://hdl.handle.net/10871/13341.

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Fish may be exposed to an array of pharmaceuticals that are discharged into the aquatic environment, paralleling advances in medical knowledge, research and technology. Pharmaceuticals by their nature are designed to target specific receptors, transporters, or enzymes. Nuclear receptors (NRs) are often a key component of the therapeutic mechanism at play, and many of these are conserved among vertebrates. Consequently, fish may be affected by environmental pharmaceutical exposure, however there has been relatively little characterisation of NRs in fish compared with in mammals. In this thesis common carp (C. carpio) were exposed to selected pharmaceuticals in vitro and in vivo to investigate effects centred on the pregnane X receptor (PXR) and peroxisome proliferator-activated receptor alpha (PPARα), two key NRs involved in organism responses to pharmaceutical exposure. The PXR acts as a xenosensor, modulating expression of a number of xenobiotic metabolising enzymes (XMEs) in mammals. In a primary carp hepatocyte model it was shown that expression of a number of XMEs was altered on exposure to rifampicin (RIF), as occurs in mammals. This response was repressed by addition of ketoconaozle (KET; PXR-antagonist), indicating possible PXR involvement. The genes analysed showed up-regulation on exposure to ibuprofen (IBU) and clofibric acid (CFA), but not clotrimazole (CTZ) or propranolol (PRP). The lack of response to mammalian PXR-agonist CTZ was unexpected. In contrast, the same XME genes were found to be up-regulated in vivo after 10 days of exposure of carp to CTZ, although this response occurred only for a relatively high exposure concentration. CTZ was found to concentrate in the plasma (with levels up to 40 times higher than the water). Development and application of a reporter gene assay to measure PXR activation in carp (cPXR) and human PXR showed CTZ activation of cPXR, supporting data from the in vivo studies. Furthermore, activation was seen at concentrations as low as 0.01 μM. Interestingly RIF did not induce a response in the cPXR reporter gene assay, contrasting with the hepatocyte culture work. Taken together, the data presented here suggests divergence in the PXR pathway between mammals and fish in terms of ligand activation and downstream gene targets. PPARα was investigated in carp in vivo using CFA as a mammalian PPARα-agonist. Overall the resulting data suggested a broadly similar role for this NR in lipid homeostasis in fish as for mammals, with a number of PPARα-associated genes and acyl-coA oxidase (ACOX1) activity up-regulated in response to CFA exposure. A number of XMEs were also up-regulated by CFA (in vivo and in vitro), potentially extending the role of PPARα in fish (carp) to regulation of xenobiotic metabolism. The work presented has provided further characterisation of PXR and PPARα in fish. Elucidation of these pathways is vital to provide meaningful data in terms of establishing toxicity and mechanism-of-action data for pharmaceuticals and other compounds in fish, to allow validation of read-across approaches and ultimately aid in their environmental risk assessment. In vitro approaches are attractive ethically, financially and can provide useful mechanistic characterisation of compounds and the primary hepatocyte model and reporter gene assays used here show potential for the screening of pharmaceutical compounds in fish. However, further understanding of the metabolism of drugs and chemicals in fish is required to establish the true value of these methods for informing on possible effects in fish, in vivo.

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45

Coxon, M. M. "Studies of pantothenate biosynthesis in Arabidopsis in vivo and in vitro." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598113.

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With a view to developing inhibitors, two enzymes of the Arabidopsis pantothenate pathway (KPHMT2 and PS) were expressed in E. coli, as MBP fusion proteins purified and used to perform kinetic studies to identify their characteristics. KPHMT2 showed an apparent Km, Vmax and kcat of 0.534 ± 0.089 mM, 0.802 ± 0.032 nmoles/min and 2.79 min/1 respectively for α-KIVA whilst the enzyme appeared to be inhibited by its co-factor, 5,10-methylene tetrahydrofolate, at levels above approximately 25μM. In addition to its potential as a target for herbicides and anti-microbials the pathway is also of commercial interest for the production of pantothenate for use as a supplement in animal feed and for addition to cosmetics. By constitutive expression of the genes of the E. coli pathway, Arabidopsis lines with higher levels of pantothenate than WT were obtained. Expression of E. coli panC resulted in increased levels of the vitamin in some lines, as did the expression of panD, however, expression of panB showed no increase. The β-alanine levels of the transgenic lines ere also assayed and showed hugely elevated levels in the lines expressing panD. To determine if expression of the E. coli genes or the accumulation of pantothenate effected the expression of the endogenous genes, RT-PCR was performed and showed no significant difference in the expression of endogenous panB2 or panC in lines expressing E. coli panB, panC or panD. Expression of the genes of the pathway was also studied using promoter:GUS fusions, RT-PCR, western blot analysis and enzyme assays. The results showed expression of the genes throughout the plant suggesting de novo pantothenate biosynthesis with panB1 and panB2 promoter activity showing up-regulation in flowers and siliques, tissues known to require large amounts of pantothenate.

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46

Rohling, Heide. "Simulation studies for the in-vivo dose verification of particle therapy." Helmholtz-Zentrum Dresden - Rossendorf, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:d120-qucosa-175213.

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An increasing number of cancer patients is treated with proton beams or other light ion beams which allow to deliver dose precisely to the tumor. However, the depth dose distribution of these particles, which enables this precision, is sensitive to deviations from the treatment plan, as e.g. anatomical changes. Thus, to assure the quality of the treatment, a non-invasive in-vivo dose verification is highly desired. This monitoring of particle therapy relies on the detection of secondary radiation which is produced by interactions between the beam particles and the nuclei of the patient’s tissue. Up to now, the only clinically applied method for in-vivo dosimetry is Positron Emission Tomography which makes use of the beta+-activity produced during the irradiation (PT-PET). Since from a PT-PET measurement the applied dose cannot be directly deduced, the simulated distribution of beta+-emitting nuclei is used as a basis for the analysis of the measured PT-PET data. Therefore, the reliable modeling of the production rates and the spatial distribution of the beta+-emitters is required. PT-PET applied during instead of after the treatment is referred to as in-beam PET. A challenge concerning in-beam PET is the design of the PET camera, because a standard full-ring scanner is not feasible. For instance, a double-head PET camera is applicable, but low count rates and the limited solid angle coverage can compromise the image quality. For this reason, a detector system which provides a time resolution allowing the incorporation of time-of-flight information (TOF) into the iterative reconstruction algorithm is desired to improve the quality of the reconstructed images. Secondly, Prompt Gamma Imaging (PGI), a technique based on the detection of prompt gamma-rays, is currently pursued. Concerning the emissions of prompt gamma-rays during particle irradiation, experimental data is not sufficiently available, making simulations necessary. Compton cameras are based on the detection of incoherently scattered photons and are investigated with respect to PGI. Monte Carlo simulations serve for the optimization of the camera design and the evaluation of criteria for the selection of measured events. Thus, for in-beam PET and PGI dedicated detection systems and, moreover, profound knowledge about the corresponding radiation fields are required. Using various simulation codes, this thesis contributes to the modelling of the beta+-emitters and photons produced during particle irradiation, as well as to the evaluation and optimization of hardware for both techniques. Concerning the modeling of the production of the relevant beta+-emitters, the abilities of the Monte Carlo simulation code PHITS and of the deterministic, one-dimensional code HIBRAC were assessed. The Monte Carlo tool GEANT4 was applied for an additional comparison. For irradiations with protons, helium, lithium, and carbon, the depth-dependent yields of the simulated beta+-emitters were compared to experimental data. In general, PHITS underestimated the yields of the considered beta+-emitters in contrast to GEANT4 which provided acceptable values. HIBRAC was substantially extended to enable the modeling of the depth-dependent yields of specific nuclides. For proton beams and carbon ion beams HIBRAC can compete with GEANT4 for this application. Since HIBRAC is fast, compact, and easy to modify, it could be a basis for the simulations of the beta+-emitters in clinical application. PHITS was also applied to the modeling of prompt gamma-rays during proton irradiation following an experimental setup. From this study, it can be concluded that PHITS could be an alternative to GEANT4 in this context. Another aim was the optimization of Compton camera prototypes. GEANT4 simulations were carried out with the focus on detection probabilities and the rate of valid events. Based on the results, the feasibility of a Compton camera setup consisting of a CZT detector and an LSO or BGO detector was confirmed. Several recommendations concerning the design and arrangement of the Compton camera prototype were derived. Furthermore, several promising event selection strategies were evaluated. The GEANT4 simulations were validated by comparing simulated to measured energy depositions in the detector layers. This comparison also led to the reconsideration of the efficiency of the prototype. A further study evaluated if electron-positron pairs resulting from pair productions could be detected with the existing prototype in addition to Compton events. Regarding the efficiency and the achievable angular resolution, the successful application of the considered prototype as pair production camera to the monitoring of particle therapy is questionable. Finally, the application of a PET camera consisting of Resistive Plate Chambers (RPCs) providing a good time resolution to in-beam PET was discussed. A scintillator-based PET camera based on a commercially available scanner was used as reference. This evaluation included simulations of the detector response, the image reconstructions using various procedures, and the analysis of image quality. Realistic activity distributions based on real treatment plans for carbon ion therapy were used. The low efficiency of the RPC-based PET camera led to images of poor quality. Neither visually nor with the semi-automatic tool YaPET a reliable detectability of range deviations was possible. The incorporation of TOF into the iterative reconstruction algorithm was especially advantageous for the considered RPC-based PET camera in terms of convergence and artifacts. The application of the real-time capable back projection method Direct TOF for the RPCbased PET camera resulted in an image quality comparable to the one achieved with the iterative algorihms. In total, this study does not indicate the further investigation of RPC-based PET cameras with similar efficiency for in-beam PET application. To sum up, simulation studies were performed aimed at the progress of in-vivo dosimetry. Regarding the modeling of the beta+-emitter production and prompt gamma-ray emissions, different simulation codes were evaluated. HIBRAC could be a basis for clinical PT-PET simulations, however, a detailed validation of the underlying cross section models is required. Several recommendations for the optimization of a Compton Camera prototype resulted from systematic variations of the setup. Nevertheless, the definite evaluation of the feasibility of a Compton camera for PGI can only be performed by further experiments. For PT-PET, the efficiency of the detector system is the crucial factor. Due to the obtained results for the considered RPC-based PET camera, the focus should be kept to scintillator-based PET cameras for this purpose.

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47

Lane, Nicholas James. "In vivo studies of ischaemia-reperfusion injury in rabbit renal autografts." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243454.

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48

Lyons, T. J. "Non-enzymatic glycosylation of collagen : In vivo and in vitro studies." Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372984.

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49

Mitchell, T. "Studies of the ethylene-forming enzyme : In vivo and in vitro." Thesis, University of Reading, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383606.

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50

Maxwell, R. J. "Nuclear magnetic resonance studies of drug metabolism and effects in vivo." Thesis, University College London (University of London), 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376471.

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Dissertations / Theses on the topic 'In vivo studies'

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