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Gezginci, Mikail Hakan. "Synthesis and in vitro antimycobacterial activity of some pyridine and pyrazinecarboxylic acid isosteres." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/284057.
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Tuberculosis has been one of the most commonly encountered infectious diseases of humans throughout history. The discovery and introduction of effective treatments in the 1940s resulted in a decline of the incidence of the disease until the 1980s, which marked a sharp turn in this trend with an increase in the number of reported cases in the world. The prevalence of mycobacterial infections in poorer nations and centers of urban decay, and especially in immunologically compromised patients indicates the need for new and better treatments. In this study, to contribute to the worldwide effort to discover more effective medications against tuberculosis, 26 previously unreported compounds were synthesized and tested against Mycobacterium tuberculosis. The synthesized compounds were designed to act as bioisosteres or prodrugs of pyridine and pyrazinecarboxylic acid derivatives and contained acidic or neutral hetero- or carbocyclic ring systems attached to pyridine or pyrazine rings at different positions. The synthesized ring systems included 1,2,4-oxadiazole-5-ones, 1,2,4-thiadiazole-5-ones, 1,2,4-oxadiazole-5-thiones, 1,3,4-oxathiazoline-2-ones and cyclobutene-1,2-diones, which were documented in the literature to act as carboxylic acid isosteres or could act as prodrugs thereof. Pivaloyloxymethyl derivatives of the compounds were also prepared in order to increase their lipophilicity and therefore improve their bioavailability. The synthesized compounds were expected to be biotransformed by esterases or amidases to the active species after penetration of the mycobacterial cell wan. Biological and pharmacokinetic properties of the compounds were compared with the unmodified polar isosteres of pyrazinoic and nicotinic acids. The majority of the tested compounds exhibited activities ranging from 0.5 to 8 times the activity of pyrazinamide, one of the lead compounds that inspired their design.
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Kumar, Malkeet. "Design, synthesis and biological evaluation of verapamil analogues, reversed isoniazids and hybrid efflux pump inhibitors against Mycobacterium tuberculosis." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/16703.
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Includes bibliographical referencesTuberculosis (TB) is one of the major infectious diseases and epidemics in the world. It is responsible for severe morbidity and mortality rates, especially in poor and resource-deficient countries. According to the World Health Organization 2014 report, about one third of the world's population is infected with tuberculosis and about 10-15% is co-infected with HIV, which further complicates the TB epidemic. Tuberculosis claims 2-3 million lives every year and is one of the biggest social and financial burdens on many countries. The disease is treatable but has been hampered by the emergence of drug resistance in the causative bacterium, Mycobacterium tuberculosis (Mtb). Resistant strains of Mtb counter the efficacy of various anti-TB drugs via mechanisms that help it overcome the toxic and inhibitory effects of these drugs. These mechanisms include mutation, enzymatic drug degradation, target modification and drug efflux. Drug efflux by efflux pumps (EPs) is one of the major mechanisms responsible for the development of drug tolerance leading to the emergence of drug resistance. These efflux pumps are regulated by the house keeping proteins present in the cell membrane of Mtb and perform a pre-existing role of rescuing the Mtb from toxic agents. These EPs extrude structurally unrelated compounds from the cell including anti-TB drugs and reduce the drug concentration to sub-inhibitory levels and aid Mtb in developing resistance. Therefore, development of antimycobacterials that target EPs and reduce their activity can be a viable strategy to reduce the global TB burden and counter the emergence of resistance. Many strategies have been used to counter the EP-mediated resistance in Mtb. In this study, two strategies were employed: (i) the development of efflux pump inhibitors (EPIs) via structural modification of a known efflux pump inhibitor, verapamil (VER), and the development of hybrid efflux pump inhibitors (HEPIs) incorporating a VER motif; and (ii) the development of antimycobacterial agents based on covalent linking or attachment of efflux pump inhibitor moieties to an anti-TB drug. These agents are termed reversed anti-TB agents and are based on isoniazid for this study.
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Mjambili, Faith Riziki. "Synthesis and biological evaluation of thiazole and metergoline derivatives as antimycobacterial and antiplasmodial agents." Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/6635.
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TB patients show poor compliance to available drugs due to the costs, adverse side effects, and prolonged treatment, leading to multi-drug resistant (MDR), extensively drug resistant (XDR), and most recently totally drug resistant TB. Shared drug toxicities and drug interactions with antiretrovirals compound the problem. The rapid development of resistance to known antimalarials compared to the rate at which new agents are coming into the market still remains a big challenge is combating malaria. Currently, with resistance to ACTs having been documented in South-East Asia, the situation is dire as there is no ready alternative to these drugs. There is thus a heightened need for research towards the development of new anti-TB and anti-malarial drugs based on novel chemotypes. Towards addressing this need, SAR studies were conducted on the 2-amino-4-aryl thiazole scaffold by synthesizing a series of derivatives with different motifs at the various positions of the scaffold. These derivatives exhibited moderate antiplasmodial activity in the CQS strain of P. falciparum, and good antimycobacterial activity on the H37Rv strain of M.tb. A 2-pyridyl group at position 4 of the thiazole ring as well as a substituted phenyl at position 2 was found to be essential for antimycobacterial activity. However, the 2-pyridyl group was not essential for antiplasmodial activity while the substituted phenyl at position 2 was essential for antiplasmodial activity. The linker between these two groups affected antimycobacterial activity with little influence on the antiplasmodial activity. In addition structural modifications were performed on the ergoline backbone of metergoline, and a number of derivatives synthesized with different para substituted phenyls. These compounds exhibited moderate antiplasmodial activity in the CQS strain of P. falciparum, and moderate antimycobacterial activity on the H37Rv strain of M.tb. The presence of a substituted phenyl group attached to the nitrogen atom of the amine was found to be essential for antimycobacterial activity, however, this substituted phenyl group didn't confer optimum antimycobacterial activity as the compounds were less active than metergoline. The antiplasmodial activity of these compounds was better than that of metergoline and was enhanced by the hydrophobicity of the substituent on the phenyl ring. Changing the linker between the ergoline backbone and the substituted phenyl ring didn't have any significant effect on either the antimycobacterial or the antiplasmodial activity.
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Njaria, Paul Magutu. "Antimycobacterial 2-aminoquinazolinones and benzoxazole-based oximes: synthesis, biological evaluation, physicochemical profiling and supramolecular derivatization." Doctoral thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/26954.
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Tuberculosis (TB) is a life-threatening infectious disease caused by Mycobacterium tuberculosis (Mtb). Globally, TB is a major public health burden with an estimated 10.4 million new cases and 1.8 million deaths reported in 2015. Although TB is curable, the treatment options currently available are beset by numerous shortcomings such as lengthy and complex treatment regimens, drug-drug interactions, drug toxicities, as well as emergence of widespread multi-drug resistance. Therefore, there is an urgent and compelling need to develop new, more effective, safer drugs with novel mechanisms of action, and which are capable of shortening treatment duration. This study focused on hit-to-lead optimization of two new classes of compounds with potential anti-TB properties: 2-aminoquinazolinones (AQZs) and benzoxazole-based oximes (BZOs). A hit compound for each of these classes with low micromolar antimycobacterial activity had previously been identified through phenotypic whole-cell in vitro screening.
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Baartzes, Nadia. "Mono- and polynuclear Ferrocenyl-derived complexes: synthesis, characterisation and biological evaluation as antimycobacterial and antiplasmodial agents." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/19973.
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Ferrocene-containing precursors, vinylferrocene and (E)-4-vinylferrocenylbenzaldehyde were prepared, by a Wittig olefination reaction and Heck cross-coupling reaction, respectively. Mononuclear ferrocenyl-derived imino complexes were synthesised by Schiff-base condensation reactions of (E)-4-vinylferrocenylbenzaldehyde with various amines. This included the preparation of a silicon-containing derivative and its carbon analogue, to determine the effect of the lipophilic moiety on the biological activity. In addition, polynuclear ferrocenyl-derived imino complexes based on the tris(2-aminoethyl)amine scaffold and the polypropyleneimine (PPI) first- and second-generation scaffolds were also synthesised using Schiff-base chemistry. These polynuclear complexes were prepared using template chemical procedures to that of the mononuclear complexes. The corresponding mono- and polynuclear ferrocenyl-derived amino complexes were synthesised via reductive amination reactions from the (E)-4-vinylferrocenylbenzaldehyde. The imine moiety was hydrogenated in order to compare the effect on the biological activity. The imino and amino complexes were isolated in moderate to high yields. A second series of ferrocenyl complexes was also prepared incorporating a thiosemicarbazone moiety, as this is a known pharmacophore and may confer favourable properties in terms of biological activity as well as solubility. Methyl hydrazinecarbodithioate was synthesised and reacted with the previously synthesised (E)-4-vinylferrocenylbenzaldehyde by a Schiff-base condensation reaction to afford a ferrocenyl dithiocarbamate. The dithiocarbamate was reacted with various amines via nucleophilic substitution reactions to give mono- and polynuclear ferrocenylthiosemicarbazone complexes. These complexes were isolated in low to moderate yields.
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MARTINS, Marta Sofia Lopes. "The antimycobacterial activity of thioridazine derivatives against drug resistant Mycobacterium tuberculosis: in vitro, ex vivo and in vivo studies." Doctoral thesis, Instituto de Higiene e Medicina Tropical, 2008. http://hdl.handle.net/10362/61780.
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O objectivo principal desta tese foi o de avaliar a acção da tioridazina (TZ), bem como de compostos derivados desta, obtidos por manipulação química, como agentes com actividade contra Mycobacterium tuberculosis, em particular contra M. tuberculosis
multi-resistente (MDR-TB). Desta forma foram obtidos vinte e dois derivados e efectuados testes de toxicidade e mutagenicidade pelo método de exclusão com azul de trypan (realizado em linfócitos humanos) e o teste de Ames, respectivamente. Todos os derivados não tóxicos e não mutagénicos foram testados in vitro contra estirpes de
Staphylococcus aureus resistente à meticilina (MRSA), que foi o microrganismo modelo utilizado durante todo o trabalho, e estirpes de MDR-TB. Visto que a tuberculose é uma infecção do macrófago alveolar, estes estudos foram subsequentemente aplicados a macrófagos infectados. Desta forma, é importante analisar a actividade que estes compostos apresentam dentro do macrófago, local onde
normalmente a micobactéria se encontra. Iniciaram-se estudos animais com a TZ, de forma a verificar a eficácia deste composto em curar murganhos Balb/C infectados com M. tuberculosis H37Rv ATCC27294. Desta forma foi possível optimizar parâmetros, tais como, a via de infecção, a concentração de composto a administrar, entre outros. Os
resultados obtidos demonstraram que dos vinte e dois derivados nenhum apresentava toxicidade ou efeitos mutagénicos, nas condições testadas. Desta forma, os vinte e dois derivados foram seleccionados para estudos in vitro contra estirpes de S. aureus e de M. tuberculosis. Dos estudos in vitro foi possível verificar que seis derivados apresentaram uma maior actividade do que a TZ e desta forma foram seleccionados para os estudos ex vivo. Quando testados em macrófagos infectados três derivados demonstraram um efeito
marcado na activação das células fagocitárias (“enhancement of the killing activity”), sendo um dos derivados ainda mais activo do que a TZ. Dos estudos em animais, foi possível seleccionar as condições a serem implementadas em estudos futuros com os derivados mais activos. De todos os resultados obtidos durante esta tese foi possível desenvolver um modelo baseado na interacção do macrófago com a bactéria e a
subsequente acção destes compostos. O modelo desenvolvido (“macrophage model”) pode assim contribuir para clarificar o que ocorre a nível intracelular aquando da adição dos compostos ao meio de cultura.The main objective of this Thesis was to evaluate thioridazine (TZ) and chemically derived derivatives for anti-Mycobacterium tuberculosis activity in particular against multi-drug resistant (MDR) M. tuberculosis. Twenty-two TZ derivatives were obtained and screened for toxicity and mutagenicity by the trypan blue exclusion assay in human lymphocytes and the Ames test, respectively. The derivatives that were devoid of any toxicity and mutagenicity were then tested against Methicillin-resistant Staphylococcus aureus (MRSA) used as a model during the entire work, and against antibiotic resistant M. tuberculosis (MDR-TB) strains in vitro and subsequently in the macrophage that has phagocytosed the organism. Since tuberculosis is an infection of the alveolar macrophage it is important to evaluate the activity of these compounds inside the phagocytic cell where the mycobacteria are to be found. Thioridazine was also tested for its ability to cure the mouse of infection by M. tuberculosis. Therefore, animal studies using Balb/C mice infected with M. tuberculosis H37Rv ATCC27294 strain were initiated to parameterize the route of infection, dose of compound to be administered, among others. The results obtained showed that from the twenty-two TZ derivates none was toxic or mutagenic under the conditions tested. Therefore, all the twenty-two derivatives were selected for in vitro evaluation against S. aureus and M. tuberculosis strains. From the in vitro results six derivatives showed greater activity than TZ and were selected for ex vivo studies. Three of these derivatives were shown to enhance the macrophage killing activity and one of the derivatives was even more active than TZ. From the animal studies it was possible to select the conditions to apply in further studies with the most active derivatives. From all the data obtained during this Thesis it was possible to develop a model based on the macrophage interaction with the bacteria and the subsequent action of the compounds. The macrophage model can elucidate what takes place inside the human macrophage when these compounds are added to the medium. Due to the uniqueness of the approaches developed during the Thesis research, other potential sources of anti-tubercular compounds were explored: plants and organosilicon compounds (SILA). These studies demonstrated that extracts from the nuisance plant Carpobrotus edulis could enhance the killing of intracellular bacteria such as MDR-TB and MRSA. In addition, the extract was shown to modulate the immune system thereby indicating its potential use for cellular immune deficient disorder as well as render MDR mouse lymphoma cells carrying the human mdr1 gene completely susceptible to cytotoxic drugs to which they were initially resistant. The results of this component of my research have resulted in the design of new experiments which are now being carried out by another Ph.D. student in our Unit and at the Medical University of Szeged, Hungary. In conclusion, the results obtrained from my Thesis research has paved the way for clinical trial consideration of the many compounds studied shown to have significant intracellular activity against XDR-TB/MDR-TB at concentrations that are non-toxic and that can be readily achieved in the infected human.
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Sahile, Henok Asfaw [Verfasser]. "Design, synthesis and biological evaluation of two classes of antimycobacterial cyclic hexa(depsi)peptides / Henok Asfaw Sahile." Halle, 2017. http://d-nb.info/1142920453/34.
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Van, Rensburg Lyne. "Antimycobacterial agents : a study of Liposomal-Encapsulation, comparitive permeability of bronchial tissue and in vitro activity against mycobacterium tuberculosis isolates." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71868.
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Thesis (MScMedSc)--Stellenbosch University, 2012.Includes bibliography
ENGLISH ABSTRACT: In this thesis, research results are reported on the role of dipalmitoyl phosphatidyl choline (DPPC) and DPPC-liposomes on the in vitro permeability characteristics of various antimycobacterial drugs across porcine bronchial tissue. The permeability flux values of the different compounds (isoniazid, ofloxacin and moxifloxacin) and their relevant DPPC formulations were determined using a continuous flow through perfusion system. Mean steady state flux values were compared statistically by means of a t-test at a significance level of 5% as well as an F-test using whole curve comparisons. The results indicated that the different formulations of drug and their DPPC combinations retard the permeation of drug through bronchial tissue. However, moxifloxacin permeation was significantly enhanced when in a DPPC-liposomal formulation. These results demonstrate the important role that molecular weight, electrostatic charge, partitioning of the molecules in DPPC and DPPC-liposomes play in transmembrane diffusion. In addition, the effect of individual drugs and their DPPC combinations on the surface tension lowering property of DPPC was evaluated. The results obtained showed minimal decreases in the surface tension lowering capability of DPPC; however, the minimal increases in surface tension do not alter the integrity of DPPC to a large extent. Drug susceptibility testing of Mycobacterium tuberculosis cultures against the individual antitubercular drugs and their DPPC combinations was done by using the Radiometric BACTEC 460TB™ system. Drug-entrapped DPPC liposomes were tested at concentrations comparable to their relative minimum inhibitory concentrations (MIC). The results for the BACTEC assay indicated that the mycobacteria were susceptible to the developed drug entrapped liposomes; of which their encapsulation efficiencies for the relevant drugs were approximately ± 50%. It was concluded that drug-entrapped DPPC liposomes could fulfill the dual role of pulmonary drug delivery and alveolar stabilization due to antiatelectatic effect of DPPC which can improve the distribution of anti-tubercular drugs in the lung
AFRIKAANSE OPSOMMING: Hierdie tesis doen verslag oor navorsingsresultate met betrekking tot die rol van dipalmitoïel-fosfatidiel-cholien (DPPC) en DPPC-liposome in die in vitro-permeasiekenmerke van verskeie antimikobakteriese middels oor vark- brongiale weefsel. Die permeasievloedwaardes van die verskillende verbindings (isoniasied, ofloksasien en moksifloksasien) en hul betrokke DPPC-formules is met behulp van ’n deurlopende-deurvloei-perfusiestelsel bepaal. Gemiddelde vloedwaardes in ’n bestendige staat is statisties vergelyk met behulp van ’n t-toets op ’n beduidendheidsvlak van 5%, sowel as ’n F-toets met behulp van heelkurwevergelykings. Die resultate dui daarop dat die verskillende middelformules en hul DPPC-kombinasies middelpermeasie oor brongiale weefsel vertraag. Tog is die permeasie van moksifloksasien aansienlik versterk in ’n DPPC-liposomale formule. Hierdie resultate bevestig die belangrike rol van molekulêre gewig, elektrostatiese lading, die verdeling van molekules in DPPC sowel as DPPC-liposome in transmembraandiffusie. Daarbenewens is die uitwerking van individuele middels en hul DPPC-kombinasies op die oppervlakspanningsverligtingsvermoë van DPPC beoordeel. Die resultate toon minimale afnames in die oppervlakspanningsverligtingsvermoë van DPPC. Die minimale toenames in oppervlakspanning het egter meestal geen noemenswaardige effek op die integriteit van DPPC gehad nie. Voorts is die vatbaarheid van Mycobacterium tuberculosis-kwekings vir die individuele anti-tuberkulêre middels en hul DPPC-kombinasies met behulp van die radiometriese BACTEC 460TB™-stelsel getoets. Middel-ingeslote DPPC-liposome is getoets in konsentrasies wat met hul relatiewe minimum inhibisiekonsentrasies (MIK) vergelyk kan word. Die resultate van die BACTEC-toets toon dat die mikobakterieë vatbaar was vir die ontwikkelde middel-ingeslote liposome, met ’n enkapsuleringsdoeltreffendheid van ongeveer 50% vir die betrokke middels. Die studie kom tot die gevolgtrekking dat middel-ingeslote DPPC-liposome die dubbele rol van pulmonêre middel-lewering en alveolêre stabilisering kan vervul weens die anti-atelektatiese werking van DPPC, wat die verspreiding van anti-tuberkulêre middels in die long kan verbeter.
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Anissian, H. Lucas. "In vitro evaluation of hip prostheses /." Stockholm, 2001. http://diss.kib.ki.se/2001/20010420anis/.
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Yamamoto, Akiko. "Biocompatibility evaluation of metallic biomaterials in vitro." Kyoto University, 1998. http://hdl.handle.net/2433/182365.
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Nathanaelsson, Lena, and Linda Sandström. "Statistical evaluation of in vitro gas production kinetics." Thesis, Umeå universitet, Institutionen för matematik och matematisk statistik, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-51348.
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At the Forage Research Centre, Swedish University of Agricultural Sciences in Umeå a technique has been developed to describe the degradation of feeds in ruminant animals. The development of this technique has been made in collaboration with Dr J.W. Cone, Nutrition and Food, Animal Sciences Group of Wageningen UR, Lelystad, the Netherlands. Experiments have been performed in laboratories where feed samples have been incubated with rumen fluid and the amount of gas produced during the digestion has been measured continuously. These feed samples were analysed at three separate occasions. The purpose of this thesis was to identify and describe statistical procedures for detecting differences between feeds analysed within the same laboratory as well as differences between the same feeds analysed in two different laboratories (in Sweden and the Netherlands). To determine the rate of digestion and to describe to what extent feeds are digested in the rumen a gas production model was fitted, using non linear regression. In order to test whether there are significant differences between the feeds, three methods were applied. For each method, the variances were estimated differently. In the first method, Hotelling’s T2 tests and two sample t tests were performed. From these tests, differences between the feeds that were analysed within the same laboratory were detected whereas no differences between the same feeds analysed in two different laboratories could be found. In the other two methods, tests were performed using an assumption of normality. These two methods detected a larger number of differences between the feeds than the first method, primarily due to extremely underestimated variances. The first method is to be preferred since the estimated variances in this method are unbiased. This causes the result to be more reliable. For future experiments it is recommended that the feed samples are analysed at considerably more than three occasions. This would lead to better estimations in the first method and consequently the result would be enhanced.
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Farrell, Laura-Lee Amelia Catherine. "Prosthetic Vein Valve: Delivery and In Vitro Evaluation." Thesis, Available online, Georgia Institute of Technology, 2007, 2007. http://etd.gatech.edu/theses/available/etd-04042007-180135/.
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Falomo, Olajumoke. "In vitro Evaluation of Resistant Starch Using Corn." OpenSIUC, 2016. https://opensiuc.lib.siu.edu/theses/1939.
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The interest in study of resistant starch in the pig nutrition is increasing. This experiment was done to evaluate resistant starch content in maize/corn by using an in vitro method. A total of 27 varieties of corn were used in this trial to determine the evaluation of in vitro resistant starch (RS); in vitro non-resistant starch (NRS); in vitro total starch (TS); dry matter (DM); ash and organic matter (OM). All treatments of corn samples were carried out in triplicates. In vitro determination of RS, NRS and TS were determined directly before the spectrophotometer reading with a wavelength of 510 nm. In vitro RS, NRS and TS ranged from 0.56 – 1.98%, 22.11 – 52.33% and 22.69 – 54.27% respectively; DM, Ash and OM ranged from 85.71 – 95.34%, 1.1 – 1.85% and 98.15 – 98.9% respectively. In RS, 424L and 5660 (P/≤/0.05); in NRS, 652N and MC 4050 (P/≤/0.01; in TS, 652N, MC 4050 and 424L (P/≤/0.01, 0.01 and 0.05 respectively); and in DM, 590 (P/≤/0.05). Results indicated that varieties of corn used may be low in amylose content because the RS values were negligible (≤ 1%) giving MC 5800 and 652N as the lowest RS values suitable for growing pigs. Further work is needed to validate these results. Keywords: In vitro; Resistant starch; Corn samples; Non-resistant starch; Total starch; Spectrophotometer
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Volden, Matthias [Verfasser]. "Ofatumumab: Evaluation of in-vitro response mechanisms / Matthias Volden." Ulm : Universität Ulm. Medizinische Fakultät, 2014. http://d-nb.info/1054401446/34.
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Reader, S. J. "Evaluation of in vitro assay for metabolism-mediated toxicology." Thesis, University of Nottingham, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384371.
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Kulkarni, Upendra D. "Optimization of porcine buccal mucosa for in vitro evaluation." Scholarly Commons, 2007. https://scholarlycommons.pacific.edu/uop_etds/652.
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Porcine buccal mucosa has been extensively used as in vitro model to study the permeability of drugs and assess their potential to deliver through buccal route. Porcine buccal mucosa is found to be very similar to human oral mucosa in structure and function. However, the in vitro permeation studies across porcine buccal mucosa show high variability which is mostly due to the various experimental and biological variables that are often overlooked while conducting such studies.
The precise nature of the permeability barrier offered by the various tissue layers of buccal mucosa was investigated in this study. It was observed that the permeability of model diffusants decreased significantly with an increase in the connective tissue layer. However, the epithelium offered a stronger barrier to permeation of all diffusants studied at mucosal thickness of up to 500 |tm. The epithelium acted as a stronger barrier for hydrophilic diffusants when compared to lipophilic diffusants.
It was also observed that the permeability of model diffusants was significantly higher in the region behind lip when compared to the middle cheek region which is due to lower epithelial thickness in that region. Porcine buccal mucosa retained its integrity in Kreb's bicarbonate Ringer solution at 4 °C for 24 hours and many other storage conditions resulted in loss of epithelial integrity. Separation of epithelium from the underlying connective tissue by heat treatment, did not adversely affect its permeability and integrity characteristics.
Influence of experimental temperature on the permeability of model compounds across porcine buccal mucosa was also investigated in vitro. An exponential relationship was observed between the apparent permeability and temperature. It was found that the activation energy of diffusion of the model compounds decreased linearly with increasing distribution coefficients across porcine buccal mucosa. This suggested that the buccal mucosa acted as a stronger barrier for diffusion of hydrophilic diffusants when compared to the lipophilic diffusants.
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Chauvel-Lebret, Dominique. "Evaluation in vitro de la biocompatibilite de materiaux elastomeres." Rennes 1, 2001. http://www.theses.fr/2001REN1B084.
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Pariente, Jean-Louis. "Evaluation in vitro de la biocompatibilité des endoprothèses urétérales." Bordeaux 2, 1997. http://www.theses.fr/1997BOR28534.
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Stoll, Matthias [Verfasser], and Elmar [Akademischer Betreuer] Hellwig. "Evaluation eines neuen Modelles zur In-vitro Testung von Endometriegeräten." Freiburg : Universität, 2007. http://d-nb.info/1123427372/34.
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Ruan, Jianming. "Characterisation and biocompatibility evaluation of calcium phosphate biomaterials in vitro." Thesis, University of Strathclyde, 2000. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=21172.
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Medical applications of calcium phosphate biomaterials are limited because of poor mechanical properties and acute inflammation reactions which take place occasionally in the clinic. To increase the usefulness of calcium phosphate biomaterials it is necessary to improve the mechanical properties and biological character. Processing and characterization of porous hydroxyapatite (HA) and dense composite (HA-Spinel) biomaterials have been performed in the present research. Biocompatibility of these biomaterials has been examined in vitro using human and rat immortalized osteoblast cells, and the advantages and limitations of cell culture biocompatibility tests are discussed. X-ray analysis of material structure demonstrated that after sintering at 1450°C, HA-Spinel was changed into tricalcium phosphate (TCP)-Spinel phase structure. Mechanical properties testing showed that the bending strength and compressive strength of HA may be improved by adding Spinel. Biocompatibility examination demonstrated that both human and rat osteoblast cells anchored to the surface of the porous and dense biomaterials in a short time, and subsequently, grew and proliferated normally on the surface of these biomaterials. Cytotoxicity evaluation in vitro by studying material extracts demonstrated that compared with the control group of cells cultured on polystyrene, HA-Spinel possessed slight toxicity. Cell growth in HA-Spinel first extracts was slightly impaired. Tritium labeling and immunofluorescent analysis proved that human osteoblast cells and rat osteoblast cells have normal expression of collagen synthesis on the above biomaterials. Confocal laser scanning microscopy (CLSM) observation showed that collagen fibers were produced on these materials, and the amount of the collagen synthesized on the materials increased with culture time. Subsequent analysis indicated that both HA and HA-Spinel can strongly adsorb serum and albumin proteins from culture media and the amount of protein adsorption was proportional to the porosity in the materials. Protein adsorption on the material surface was saturated usually in 2-4 hours, and 1/3-1/2 of the total protein adsorption was achieved in several minutes. In vitro assay also confirmed that human and rat osteoblast cells can be applied as an in vitro model to evaluate the biocompatibility, cytotoxicity and other biological characteristics. Compared with human osteoblast cells, rat osteoblast cells have a greater proliferation rate. In normal conditions, the proliferation rate of the rat osteoblast cells is 2-4 times that of the human osteoblast cells and for this reason rat osteoblasts seem more sensitive to material extracts.
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Dolati, Farzaneh. "In vitro evaluation of carbon-nanotube-reinforced bioprintable vascular conduits." Thesis, The University of Iowa, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1573577.
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Vascularization of thick engineered tissue and organ constructs like the heart, liver, pancreas or kidney remains a major challenge in tissue engineering. Vascularization is needed to supply oxygen and nutrients and remove waste in living tissues and organs through a network that should possess high perfusion ability and significant mechanical strength and elasticity. In this thesis, we introduce a fabrication process to print vascular conduits directly, where conduits were reinforced with carbon nanotubes (CNTs) to enhance their mechanical properties and bioprintability. The generation of vascular conduit with a natural polymer hydrogel such as alginate needs to have improved mechanical properties in order to biomimic the natural vascular system. Carbon nanotube (CNT) is one of the best candidates for this goal because it is known as the strongest material and possesses a simple structure.
In this thesis, multi-wall carbon nanotube (MWCNT) is dispersed homogenously in the hydrogel and fabricated through an extrusion-based system.In vitro evaluation of printed conduits encapsulated in human coronary artery smooth muscle cells was performed to characterize the effects of CNT reinforcement on the mechanical, perfusion and biological performance of the conduits. Perfusion and permeability, cell viability, extracellular matrix formation and tissue histology were assessed and discussed, and it was concluded that CNT-reinforced vascular conduits provided a foundation for mechanically appealing constructs where CNTs could be replaced with natural protein nanofibers for further integration of these conduits in large-scale tissue fabrication. It was concluded that MWCNT has a significant effect on mechanical properties, vascular conduit swelling ratio and biological characterization in short-term and long-term cellular viability.
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Ho, K. K. L. "An in vitro and in vivo evaluation of venturi nebulisers." Thesis, Cardiff University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381229.
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Jacqueline, Cédric Potel Gilles. "Evaluation expérimentale des nouveaux antistaphylococciques corrélation in vitro - in vivo /." [S.l.] : [s.n.], 2003. http://theses.univ-nantes.fr/thesemed/DOCjacqueline.pdf.
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Stoll, Matthias. "Evaluation eines neuen Modelles zur In-vitro Testung von Endometriegeräten." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:25-opus-45419.
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Tranchier, Christine. "Evaluation de la toxicité aigüe "in vivo" et "in vitro"." Paris 5, 1989. http://www.theses.fr/1989PA05P016.
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Jacqueline, Cédric. "Evaluation expérimentale des nouveaux antistaphylococciques : corrélation in vitro - in vivo." Nantes, 2003. http://www.theses.fr/2003NANT24VS.
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Les bactéries à Gram positif sont au cœur des préoccupations actuelles en raison de leur multirésistance aux antibiotiques. La fréquence encore élevée des souches de Staphylococcus aureus résistantes à la méticilline (SARM) à l'hôpital, l'émergence de souches de sensibilité diminuée aux glycopeptides et la récente apparition de souches résistantes à la vancomycine (CMI >32mg/L) n'ont fait que renforcer le besoin de nouvelles molécules antistaphylococciques insensibles à ces mécanismes de résistance. Deux molécules récentes, le linézolide et la quinupristine-dalfopristine, sont actuellement disponibles sur le marché. A l'aide du modèle d'endocardite expérimentale du lapin, nous avons montré que l'administration en perfusion continue (à débit constant) du linézolide était supérieure au mode d'administration recommandé pour cette molécule (administration IV de 600 mg 2 fois par jour) sur trois souches de SARM. La quinupristine-dalfopristine a démontré une activité bactéricide sur deux souches de SARM (ermA- and ermA+) dans ce même modèle ; L'addition de gentamicine n'a pas permis d'augmenter l'efficacité antibactérienne, que ce soit en terme de réduction de la charge bactérienne dans la végétation ou de prévention de la sélection de mutants-résistants. L'étude in vitro des associations incluant le linézolide a permis de mettre en évidence un antagonisme avec la vancomycine et la gentamicine, essentiellement sur la phase de bactéricidie précoce de l'aminoside. Une indifférence a été observée avec le linézolide en association avec la rifampicine. Face à l'antagonisme observé in vitro pour la gentamicine, cette association a été étudiée in vivo sur deux souches de SARM sensibles à cet antibiotique. Contrairement aux résultats in vitro, l'association linézolide + gentamicine a démontré une activité bactéricide (>4 log10 UFC/g végétation) sur ces souches et apparaît capable de stériliser les végétations aortiques après trois jours de traitementGram-positive bacteria resistant to almost all of the available antibacterials have been identified. The incidence of methicillin-resistant Staphylococcus aureus (MRSA) remains very high in hospitals. Moreover, the emergence of MRSA strains with reduced susceptibility to glycopeptides and the recent appearance of vancomycin resistant strains (MIC >32mg/L) have emphasized the need for new active drugs. Two new anti-staphylococcal agents, linezolid and quinupristin-dalfopristin, are now available. Using the rabbit endocarditis experimental model, we showed that linezolid continuous infusion (at a constant rate) exhibit a bactericidal activity on three MRSA strains whereas intermittent dosing (twice a day) did not. Quinupristin-dalfopristin showed a bactericidal activity on two MRSA strains (ermA- and ermA+) in the same experimental model. Antibacterial activity in aortic vegetations and prevention of resistant variants were not increased by the addition of gentamicin. In vitro studies of combinations including linezolid showed an antagonism with vancomycin and gentamicin, mainly on the early bactericidal activity of the aminoglycoside. Linezolid, in combination with rifampin, exhibited an additive interaction. In reason of in vitro antagonism, we compared the in vivo activity of linezolid alone and in combination with gentamicin against two gentamicin-susceptible MRSA strains. In contrast to in vitro observations, linezolid + gentamicin appeared highly efficacious with a decrease of at least 4 log10 CFU/g of vegetation. Moreover, the combination was able to sterilize the aortic vegetations after a 3-day treatment
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Dolati, Farzaneh. "In vitro evaluation of carbon-nanotube-reinforced bioprintable vascular conduits." Thesis, University of Iowa, 2014. https://ir.uiowa.edu/etd/1447.
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Vascularization of thick engineered tissue and organ constructs like the heart, liver, pancreas or kidney remains a major challenge in tissue engineering. Vascularization is needed to supply oxygen and nutrients and remove waste in living tissues and organs through a network that should possess high perfusion ability and significant mechanical strength and elasticity. In this thesis, we introduce a fabrication process to print vascular conduits directly, where conduits were reinforced with carbon nanotubes (CNTs) to enhance their mechanical properties and bioprintability. The generation of vascular conduit with a natural polymer hydrogel such as alginate needs to have improved mechanical properties in order to biomimic the natural vascular system. Carbon nanotube (CNT) is one of the best candidates for this goal because it is known as the strongest material and possesses a simple structure.
In this thesis, multi-wall carbon nanotube (MWCNT) is dispersed homogenously in the hydrogel and fabricated through an extrusion-based system.In vitro evaluation of printed conduits encapsulated in human coronary artery smooth muscle cells was performed to characterize the effects of CNT reinforcement on the mechanical, perfusion and biological performance of the conduits. Perfusion and permeability, cell viability, extracellular matrix formation and tissue histology were assessed and discussed, and it was concluded that CNT-reinforced vascular conduits provided a foundation for mechanically appealing constructs where CNTs could be replaced with natural protein nanofibers for further integration of these conduits in large-scale tissue fabrication. It was concluded that MWCNT has a significant effect on mechanical properties, vascular conduit swelling ratio and biological characterization in short-term and long-term cellular viability.
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Wu, Calvin. "In Vitro Cortical Networks for Disease Modeling and Drug Evaluation." Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407860/.
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In translational research, disease models in preclinical studies are used as media for discovery of drugs or novel therapeutics. Development of in vitro models for various neurological diseases that enable efficient pharmacological or toxicological screening has been ongoing but challenging. Recognizing the potential benefit of in vitro disease models, dysfunctions in the cortical neuronal networks were induced to mimic the functional pathology of neurological symptoms using microelectrode arrays. Two different disease states – tinnitusand excitotoxicity – were investigated and discussed. In this model, pentylenetetrazol-induced increase in spontaneous firing rate and synchrony in the auditory cortical networks was used as correlate of tinnitus. Potential tinnitus treatment drugs from several different classes – including the novel class of potassium channel openers – were screened and quantified. The potentialtherapeutic values of these drugs were also discussed as the basis for drug repurposing. Functional excitotoxicity was induced by cisplatin (a cancer drug that causes neurological sideeffects) and glutamate (the major excitatory neurotransmitter). As proof-of-principle that the model may contribute to expediting the development of therapeutics, cisplatin excitotoxicity wasprevented by the antioxidant D-methionine, while glutamate excitotoxicity was prevented by ceftriaxone (a modulator of a glutamate reuptake transporter). In the latter part of the study, with results linking two of the screened drugs L-carnitine and D-methionine to GABAA receptor activation, it was demonstrated that this model not only served as an efficient drug-screening platform, but can be utilized to functionally investigate the underlying mechanism of drugs. Inaddition, several practical or conceptual directions for future studies to improve on this in vitro disease model are suggested.
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Müller, Cristina. "Synthese und in vitro Evaluation funktionalisierter Steroide markiert mit Tc99m Diplomarbeit /." Zürich : ETH, Eidgenössische Technische Hochschule Zürich, Departement Angewandte Biowissenschaften, Institut für Pharmazeutische Wissenschaften, 2000. http://e-collection.ethbib.ethz.ch/show?type=dipl&nr=13.
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Arnold, Yvonne. "Synthese und in vitro Evaluation von organometallischen Inhibitoren der humanen Thymidinkinase." Zürich : ETH, Eidgenössische Technische Hochschule Zürich, Departement Angewandte Biowissenschaften, Institut für Pharmazeutische Wissenschaften, 2003. http://e-collection.ethbib.ethz.ch/show?type=dipl&nr=113.
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Arnold, Stephanie Lorraine. "An in vitro evaluation of DBM as a tissue engineered scaffold." Connect to this title online, 2007. http://etd.lib.clemson.edu/documents/1193079966/.
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Etemadi, S. "In vivo and in vitro evaluation of resin-bonded porcelain restorations /." Title page, Contents and Summary only, 1996. http://web4.library.adelaide.edu.au/theses/09DM/09dme83.pdf.
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Yan, Jing. "In-vitro evaluation of a lyophilised nasal dosage system containing chlorhexidine." Thesis, University of Strathclyde, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.502306.
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The aim of this research project was to examine the in-vitro properties of a nasal insert formed from a lyophilised viscous hydroxyproylmethylcellulose (HPMC) gel solution designed to deliver chlorhexidine intranasally to prevent MRSA colonisation. In-vitro drug release tests indicated that the chlorhexidine release rate is influenced by the molecular weight and concentration of HPMC and the presence of mannitol. Increasing the HPMC molecular weight and concentration made it more difficult for the drug to release from the matrix and reduced the release rate; as there could be more HPMC molecules in unit volume which means more polymer matrix. Adding mannitol resulted in faster release of chlorhexidine, as mannitol dissolves in water and creates niore pathways for the drug to diffuse through. In-vitro dynamic adhesion tests were carried out on an agar/mucin plate which was designed to mimic the movement of the formulation over the nasal mucosa. Results indicated that increasing the HPMC molecular weight and concentration increased adhesion to this synthetic mucosal surface.
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Engels, Anne-Cathrin [Verfasser], and Martin [Akademischer Betreuer] Schenk. "In vitro Evaluation donorspezifischer Transplantattoleranz / Anne-Cathrin Engels ; Betreuer: Martin Schenk." Tübingen : Universitätsbibliothek Tübingen, 2017. http://d-nb.info/1199615277/34.
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Alekseev, Denis [Verfasser]. "In- vitro- evaluation der Open Loop Albumin Dialysis (OLAD) / Denis Alekseev." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1047097400/34.
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Van, der Merwe Carel. "In vitro evaluation of root canals obturated with four different techniques." Diss., Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-01252010-105530/.
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Lopes, Jennifer. "IN VITRO EVALUATION OF A DIFFERENTIAL REFLECTOMETRY DENTAL CALCULUS DETECTION INSTRUMENT." Master's thesis, Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/437247.
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Oral BiologyM.S.
Objectives: The presence of subgingival dental calculus on tooth root surfaces, an important risk factor in the pathogenesis of human periodontitis, is clinically challenging to reliably detect with existing tactile-based, manual forms of dental instrumentation. In 2003, the United States Food and Drug Administration granted approval for marketing in the United States of a differential reflectometry-based device (DetecTar, NEKS Technologies, Laval, Quebec, Canada) for detection of subgingival dental calculus in humans. The instrument employs a light-emitting diode to deliver red light from the visible light region of the electromagnetic spectrum, with a 635 nm-specific wavelength, onto tooth root surfaces through an optical fiber extending to the tip of a periodontal probe-like handpiece. The optical fiber also collects light reflected back from oral surfaces, from which the optical signature of dental calculus is identified by matching the spectra of the reflected light to an internal computer software database containing red light spectra characteristic of dental calculus in its reference library. To date, only a limited amount of in vitro and in vivo research has been conducted on the DetecTar differential reflectometry device. As a result, the purpose of this study was to to assess, with an in vitro typodont model system, the ability of the DetecTar differential reflectometry device to reliably identify subgingival dental calculus on tooth root surfaces. Methods: A total of 108 subgingival sites on mandibular posterior plastic teeth, of which 73 (67.6%) exhibited artificial dental calculus deposits, were mounted within typodont models of the human oral cavity, comprised of white plastic teeth emerging from and surrounded by anatomically-accurate pink silicone gingival and palatal soft tissues. Each typodont was attached to a phantom head with simulated soft tissue mouth shrouds. Sheep blood was irrigated into subgingival and interproximal areas around typodont teeth to simulate gingival tissue inflammation, and artificial saliva applied onto supragingival typodont tooth surfaces to further simulate typical oral cavity conditions in humans. The 108 test subgingival surfaces were then evaluated with the DetecTar differential reflectometry device in duplicate readings performed by a single periodontist examiner blinded to the typodont distribution of subgingival dental calculus. Emission of a sustained audible signal tone from the DetecTar differential reflectometry device upon entry of its optical fiber tip into typodont periodontal pockets indicated detection of subgingival dental calculus. The diagnostic performance of the DetecTar differential reflectometry device, relative to in vitro detection of subgingival dental calculus, was assessed among all test root surfaces, as well as among proximal and non-proximal root surfaces, with calculations of sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood value, negative likelihood value, diagnostic odds ratio, accuracy (diagnostic effectiveness), and Youden’s Index. Results: Among all root surfaces, the DetecTar differential reflectometry device revealed a sensitivity of 75.4%, specificity of 86.3%, positive predictive value of 86.0%, negative predictive value of 75.9%, positive likelihood value of 5.5, negative likelihood value of 0.3, diagnostic odds ratio of 19.6, accuracy (diagnostic effectiveness) of 80.6%, and Youden’s index value of 0.62, for in vitro detection of subgingival dental calculus. More favorable diagnostic test findings for the device were found on non-proximal (buccal and lingual) than proximal (mesial and distal) root surfaces, with accuracy (diagnostic effectiveness) values 22.7% lower at proximal sites, indicating a poorer performance capability of differential reflectometry within interproximal periodontal pockets. Only a fair level (kappa = 0.42) of reproducibility was found in duplicate scoring of tooth root surfaces for subgingival dental calculus by the DetecTar differential reflectometry device. Conclusions: These study findings suggest marked limitations in the potential clinical utility of the DetecTar differential reflectometry device for detection of subgingival dental calculus. The device demonstrated markedly decreased in vitro accuracy on mesial and distal typodont tooth root surfaces, as compared to non-proximal tooth sites, and exhibited only a fair level of reproducibility in duplicate assessments. The overall performance of the DetecTar differential reflectometry device appears to be inferior to similar assessments of typodont tooth root surfaces conducted by other investigators with more conventional tactile-based, manual instrumentation. Based on these in vitro findings, routine clinical utilization of the DetecTar differential reflectometry device in dental practice is not recommended.
Temple University--Theses
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Evangelista, Fernanda Cristina Gontijo. "Evaluation of in vitro antitumor activity of triazole / azide synthetic chalcones." Instituto Nacional de Pesquisas da Amazônia, 2018. http://bdtd.inpa.gov.br/handle/tede/2639.
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Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP
Many compounds isolated from lichens exhibit biological activity, and a number of them are proven sources of antitumor drugs. Even simple structural changes to these bioactive compounds can lead to potentiation of their activity. The purposes of this study were to evaluate the antiproliferative activity and selectivity of the following compounds isolated from lichens: atranorin; diffractaic, divaricatic, perlatolic, psoromic, norstitic, protocetraric, and fumarprotocetraric acids; and alkyl derivatives. Cytotoxicity tests based on the sulforhodamine B dye were performed on seven lines of neoplastic cells and one line of normal cells (3T3)
Muitas substâncias isoladas de liquens apresentam atividades biológicas, e algumas demonstraram ser fontes promissoras de drogas antitumorais. Modificações estruturais simples a partir dessas substâncias bioativas podem levar a potencialização da atividade apresentada. Os objetivos deste estudo foram avaliar a atividade antiproliferativa e seletividade dos seguintes compostos isolados de liquens: atranorina, ácidos difractaico, divaricático, perlatólico, psorômico, norstítico, protocetrárico e fumarprotocetrárico e derivados alquílicos. O ensaio de citotoxicidade foi realizado com corante sulforrodamina B em sete linhagens de células neoplásicas e uma linhagem de células normais (3T3)
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Gourevich, Dana. "Ultrasound mediated Targeted Drug Delivery in vitro : design, evaluation and application." Thesis, University of Dundee, 2013. https://discovery.dundee.ac.uk/en/studentTheses/0a3943df-4330-44b5-9f06-814ba2379d11.
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Background Targeted Drug Delivery (TDD) is a therapeutic modality which allows an increase in the medication dose at a treatment site, while simultaneously avoiding effects in the rest of the human body. This can be achieved via different types of delivery vehicles or carriers which encapsulate the free drug and release it only at the needed location. There are various methods of drug release, one of which is ultrasound, as in ultrasound-mediated TDD (USmTDD). The combination of focused ultrasound (FUS) and magnetic resonance imaging (MRI) provides a controllable system of drug release and impact assessment.In the work reported here, a novel drug carrier was synthesized and assessed. Ultrasonic drug release from the carrier was evaluated in vitro using a clinical MRI-guided Focused Ultrasound Surgery (MRgFUS) system. As there was no properly controllable research environment for in-vitro studies available prior to the investigation of the carriers, such an environment was built and characterized.Methods MCF7 and A375m human cancer cell lines were subjected to FUS using the ExAblate 2000 and 2100 systems (InSightec, Haifa, Israel). The experiments were conducted in a specially designed research environment, which was comprehensively evaluated to ensure both cell sterility and proper FUS propagation. Various sonication parameters were applied, in conjunction with a commercially available ultrasound contrast agent (USCA), to achieve maximal cellular uptake of Doxorubicin (Dox) with minimal decrease in cell viability. A novel cyclodextrin (CD) based drug carrier was synthesized, chemically evaluated, and investigated in vitro via two release mechanisms: heating and physical effects.Results Two clinical MRgFUS systems were adapted for in-vitro work, showing controllable and repeatable results. Both of the assessed release mechanisms showed their competency: the application of FUS in the presence of USCA increased the cellular drug uptake of Dox by an average factor of 3 ±0.9, and up to a factor of 4 due to heating. The Dox release from the CD-based carrier was around 100% with both mechanisms.Conclusions Adaptation of a clinical MRgFUS system for in-vitro research allows the use of a single system starting from in-vitro studies, through the pre-clinical stage to clinical trials. This gives physicians the ability to be a part of a wider USmTDD research group, from the beginning of the product definition, bringing real meaning to the term “from bench to bedside”. The baseline studies reported here have verified that intracellular drug uptake is increased through heating and sonoporation processes. The release mechanisms from the carriers were also observed, validating the concept of USmTDD from CD-based carriers.
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Mallié, Michèle. "Evaluation de l'activité in vitro de divers antifongiques sur candida albicans." Montpellier 1, 1985. http://www.theses.fr/1985MON13505.
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CREUTZ, BAZIN CLEMENCE. "Evaluation in vitro de l'activite antiseptique de substances minerales peu solubles." Nancy 1, 1993. http://www.theses.fr/1993NAN1P078.
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Guigand, Martine. "Evaluation de materiaux calciques utilises en endodontie : etude comparative in vitro." Rennes 1, 1998. http://www.theses.fr/1998REN1B083.
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Russell, Craig. "Paediatric drug development : reformulation, in vitro, genomic and in vivo evaluation." Thesis, Aston University, 2014. http://publications.aston.ac.uk/25258/.
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Angiotensin converting enzyme (ACE) inhibitors lisinopril and ramipril were selected from EMA/480197/2010 and the potassium-sparing diuretic spironolactone was selected from the NHS specials list for November 2011 drug tariff with the view to produce oral liquid formulations providing dosage forms targeting paediatrics. Lisinopril, ramipril and spironolactone were chosen for their interaction with transporter proteins in the small intestine. Formulation limitations such as poor solubility or pH sensitivity needed consideration. Lisinopril was formulated without extensive development as drug and excipients were water soluble. Ramipril and spironolactone are both insoluble in water and strategies combating this were employed. Ramipril was successfully solubilised using low concentrations of acetic acid in a co-solvent system and also via complexation with hydroxypropyl-β-cyclodextrin. A ramipril suspension was produced to take formulation development in a third direction. Spironolactone dosages were too high for solubilisation techniques to be effective so suspensions were developed. A buffer controlled pH for the sensitive drug whilst a precisely balanced surfactant and suspending agent mix provided excellent physical stability. Characterisation, stability profiling and permeability assessment were performed following formulation development. The formulation process highlighted current shortcomings in techniques for taste assessment of pharmaceutical preparations resulting in early stage research into a novel in vitro cell based assay. The formulations developed in the initial phase of the research were used as model formulations investigating microarray application in an in vitro-in vivo correlation for carrier mediated drug absorption. Caco-2 cells were assessed following transport studies for changes in genetic expression of the ATP-binding cassette and solute carrier transporter superfamilies. Findings of which were compared to in vitro and in vivo permeability findings. It was not possible to ascertain a correlation between in vivo drug absorption and the expression of individual genes or even gene families, however there was a correlation (R2 = 0.9934) between the total number of genes with significantly changed expression levels and the predicted human absorption.
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Irari, Ken W. "An in-vitro evaluation of repair protocols applied to composite resin." University of the Western Cape, 2016. http://hdl.handle.net/11394/5043.
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Magister Scientiae Dentium - MSc(Dent)The shift towards minimally invasive dentistry has meant that dental practitioners are now undertaking procedures that are conservative and preserve as much of the existing tooth structure as possible. Repairing composite is a more conservative way of managing damaged restorations when compared to their replacement. A number of different protocols for repairing composite restorations exist but there is little information as to which is the most effective method. Aim: The aim of this study was to evaluate the effect the following treatment procedures have on the shear bond strength of repaired composite: i. Five different repair protocols, ii. Two different types of repair composite materials and iii. Aging in artificial saliva prior to repairing. Materials and methods: Two hundred and forty composite cylinders of 5mm diameter and 5mm height made from Filtek Supreme XTE (3M ESPE, St. Paul, MN, USA) were prepared with the aid of a silicon matrix. They were then divided into two groups: a hundred and twenty of these cylinders were aged in a solution of artificial saliva for 28 days and the remaining samples were left unchanged with no aging. All the aged and non-aged composite cylinders were then randomly allocated to six groups of twenty each corresponding to the repair protocol applied. The first group from both of the aged and non-aged samples was treated by roughening the top surface with a diamond bur followed by an application of Scotchbond 1XT (3M ESPE, St. Paul, MN, USA). The second group received a surface roughening with a diamond bur,etching with 35% phosphoric acid and application of Scotchbond 1XT. The third group received an application of Scotchbond Universal (3M ESPE, St. Paul, MN, USA) and the fourth one had a single application of Tetric N-Bond Universal (Ivoclar Vivadent AG, Schaan, Liechtenstein) on its top surface. The fifth group was treated by blasting with COJET Sand (3M ESPE, St. Paul, MN, USA) particles together with an application of Scotchbond Universal. The final group was used as the control where no surface treatment was done. After the surface treatments, each of the composite samples was repaired by the addition of fresh composite in the shape of cylinders measuring 3mm in diameter and 4mm in height. This was done with the aid of a silicon matrix. Within each treatment sub-group (n=20), 10 cylinders were repaired using either Filtek Supreme XTE or Tetric N-Ceram. All two hundred and forty repaired samples were then subjected to shear bond strength testing on a Universal testing machine. Data analysis: The results of the shear bond strength tests expressed in megapascals (MPa) were recorded and analysed for the effect of three different factors under consideration. The effectiveness of the repair protocols, type of composite and aging in artificial saliva were compared using the analysis of variance. Differences within the groups were identified using a post hoc analysis. Results: The mean highest repair shear bond strength was observed when COJET Sand in conjunction with Scotchbond Universal was used to repair the aged composite blocks. There were no significant differences in the shear bond strength observed when either Filtek Supreme XTE or Tetric N-Ceram was used as the repair composites. Aging in artificial saliva led to a mean reduction of 18.08% in the repair bond strength across the six treatment groups. Conclusions: The application of a surface treatment and intermediate adhesive is crucial in improving bond strength in the composite repair interface. Repair with Filtek Supreme XTE and Tetric N-Ceram was equally effective. Aging in artificial saliva produced significantly reduced bond strength.
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De, Hauwer Christophe. "Evaluation du comportement de cellules in vitro par traitement des images." Doctoral thesis, Universite Libre de Bruxelles, 1998. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/212010.
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Gonçalves, Marta Alves Moreira. "Micromorphology and in vitro antibacterial evaluation of Zanthoxylum and Hymenocardia species." Master's thesis, ISA/UL, 2018. http://hdl.handle.net/10400.5/17869.
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Mestrado em Engenharia Agronómica - Protecção das Plantas - Instituto Superior de AgronomiaAs plantas desenvolveram mecanismos funcionais e metabólicos como uma estratégia de defesa para sobreviver em ambientes adversos. Terpenóides, alcalóides, flavonóides e compostos fenólicos são biosintetizados e acumulados em organelos celulares ou em estruturas secretoras. Sendo assim, as plantas são uma fonte valiosa de produtos naturais e são usadas em medicina tradicional. O estudo das plantas proporciona novas ferramentas para o tratamento várias doenças e infeções. O objetivo deste trabalho foi estudar a micromorfologia da folha, atividade antibacteriana e antifúngica, potencial sinérgico e determinação do perfil fitoquímico de três espécies nativas da Guiné-Bissau, conhecidas por possuírem propriedades etnobotânicas: Zanthoxylum zanthoxyloides, Zanthoxylum leprieurii e Hymenocardia acida. O material vegetal foi recolhido na Guiné-Bissau. As folhas foram observadas em microscopia de campo claro, microscopia de fluorescência e microscopia eletrónica de varrimento. Extratos de polaridade crescente foram obtidos por extração sequencial do material vegetal e posteriormente testados contra bactérias Gram-positivas, Gram-negativas e fungos. A concentração mínima inibitória (CMI) e a concentração mínima bacteriostática (CMB) foram determinadas. O potencial sinérgico foi avaliado e o índice da concentração inibitória fracionária (ICIF) foi calculado. O perfil fitoquímico foi realizado por TLC em sílica gel. Foi possível identificar características micromorfologicas que permitem a diferenciação das espécies de Zanthoxylum. Os testes histoquímicos revelaram que as diferenças entre estas são de natureza quantitativa e não qualitativa. Para H. acida foi detetada a presença de vários compostos, sendo que os extratos apolares são os mais ativos, capazes de inibir o crescimento de bactérias Gram-positivas. Extratos de espécies de Zanthoxylum revelaram atividade contra Grampositivas e fungos, e quando combinados com antibióticos demostraram um efeito sinérgico, revertendo a atividade antibacteriana em estirpes resistentes. Os resultados obtidos enfatizam o valor de estudos adicionais para melhor compreensão dos compostos e mecanismos que podem ser fundamentais para ultrapassar a problemática da resistência das bactérias aos antibióticos
N/A
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Brand, Lucas M. DDS, Craig A. DDS Dunlap, Ray DDS MSD Scott, and Ove A. DMD MS PhD Peters. "AN IN VITRO EVALUATION OF THE WIRELE-X ELECTRONIC APEX LOCATOR." Scholarly Commons, 2021. https://scholarlycommons.pacific.edu/dugoni_etd/14.
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Aim: The aim of this study was to evaluate the accuracy of the Wirele-X (Forum Tec, Ashkelon, Israel), a new Bluetooth-enabled electronic apex locator (EAL). The accuracy of the Wirele-X and the Root ZX II (J. Morita, Tokyo, Japan) was compared in vitro using an alginate model. Materials/Methods: Thirty-one extracted single-rooted human teeth with mature apices were decoronated at the CEJ. Under 10X magnification, actual canal lengths (ACL) were determined. The teeth were embedded in alginate and electronic canal length measurements were obtained using the Root ZX II and Wirele-X EALs. Each tooth was measured three times with both EALs. A blinded examiner measured each file with a digital micrometer to the nearest 0.01 mm. Differences between ACLs and the average measurements from the EALs were compared with Student's t test for related samples. Results: The average distance from the file tip to the apical foramen (AF) was -0.11 mm (±0.16) and -0.07 mm (±0.21) for the Root ZX II and Wirele-X systems, respectively. There were no statistically significant differences between the two apex locators in their ability to locate the AF (p > 0.05). Conclusions: Both the Wirele-X and the Root ZX II provided a high level of accuracy and reliability in locating the AF.
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Barrey, Cédric. "Evaluation biomécanique d'une prothèse discale cervicale : analyses in vitro et in vivo." Phd thesis, Paris, ENSAM, 2011. http://pastel.archives-ouvertes.fr/pastel-00584788.
Full textAbstract:
Dans cette thèse, nous avons analysé le comportement biomécanique In Vitro et In Vivo d'une prothèse discale cervicale à articulation sphérique. Les expérimentations In Vitro nous ont permis d'étudier la cinématique segmentaire dans les trois plans de l'espace au niveau instrumenté et aux niveaux adjacents. La mesure de la pression intradiscale a apporté des informations sur les variations de contraintes après arthroplastie au niveau des disques adjacents. Différentes configurations ont ainsi été évaluées : arthroplastie et arthrodèse à 1 et 2 niveaux, montage hybride. L'influence de la précharge sur le comportement biomécanique du rachis cervical a fait l'objet d'un travail spécifique en se basant sur les essais In Vitro et sur la simulation numérique. Les analyses In Vivo 2D ont été effectuées sur des clichés dynamiques en flexion-extension et ont permis le calcul des amplitudes de mobilité et de la position des centres moyens de rotation dans une population de patients opérés (n=32). Celles-ci ont intéressé le niveau opéré mais également les niveaux adjacents à court et moyen terme. Grâce au système stéréo-radiographique EOSTM, nous avons pu compléter l'analyse cinématique In Vivo par la mesure des amplitudes de mobilité des segments instrumentés dans les trois plans de l'espace.
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Renner, Jan Frederik. "In vitro-Evaluation kombinierter immunologischer und pharmakologischer Therapiestrategien zur Behandlung des Pankreaskarzinoms." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-50130.
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Liao, Yu Huan. "Evaluation of insulin secretion by in vitro generated human islet-like clusters." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/2511.
Full textAbstract:
Type 1 diabetes is an autoimmune disease in which patients' insulin-secreting beta cells in pancreatic islets are destroyed by their own immune system, leading to unregulated blood glucose levels and severe complications. Its only treatment is intensive insulin therapy, which carries the risk of hypoglycemic episodes and can result in seizures, coma, and even death. Islet transplantation has recently become an alternative, albeit experimental, treatment for type 1 diabetes patients. More than one donor graft is usually required to render recipients insulin independent, making the shortage of donor tissue an extremely important challenge in islet transplantation. Identifying the cell type that has the ability to differentiate into islet-like tissue is an important area of study.
In this study, I hypothesized that insulin secreting human islet-like clusters could be generated from pancreatic ductal cells, a potential pancreatic progenitor cell type. Islet-like clusters were generated using crude exocrine tissue from human cadaveric donors. This crude exocrine tissue contained a large number of ductal cells, as well as other pancreatic cell types. To evaluate insulin secretion by human islet-like clusters, a static incubation system was set up and tested using Min6 cells, a known insulin-secreting cell line. Using static incubation, significant increases in insulin secretion by islet-like clusters were observed when the clusters were exposed to higher glucose levels and GLP-1, a known insulin secretagogue. Presence of corresponding C-peptide secretion demonstrated that de novo insulin secretion occurred. Furthermore, basal insulin secretion increased as culture stages progressed. An attempt was made to generate islet-like clusters using ductal cells purified by fluorescent activated cell sorting or magnetic activated cell sorting. Nevertheless, it was difficult to ensure survival and proliferation of purified ductal cells. Further studies will be necessary to confirm the role of ductal cells in the generation of islet-like clusters using the crude exocrine tissue, as well as to identify factors that can promote ductal cells proliferation after cell sorting.