• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 9
  • 3
  • 2
  • 2
  • 2
  • 2
  • Tagged with
  • 24
  • 24
  • 7
  • 6
  • 6
  • 5
  • 4
  • 4
  • 4
  • 4
  • 4
  • 3
  • 3
  • 3
  • 3
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Structural Optimization of Bell Crank using Adaptive Response Surface Optimization

Konda Ram Kumar, Ram Suraj 04 June 2024 (has links)
This research contributes to the development of a structural optimization software system designed to support design optimization. The focus of this thesis work is on formulating strategies to obtain accurate solutions and enhance the efficiency of the optimization process, particularly when dealing with large and complex finite element (FE) models, utilizing statistical concepts. A potential avenue explored in this study is the adaptive response surface optimization process. The adaptive response surface optimization method involves the adaptive control of samples selected through the design of experiments and empirical models constructed via the response surface methodology, with the sampling of the design space and empirical model terms dynamically adjusted throughout the optimization progression. The empirical models are constructed with statistically significant terms to maximize the utilization of information from each sample generated using the design of experiments. If the available information is fully utilized by the empirical model and the adaptive response surface optimization process needs to progress further until an optimal solution is identified, additional samples are generated. The methodology is applied to a benchmark bell crank problem, optimizing the bell crank for maximum operational value by simultaneously increasing fatigue life and reducing the overall component cost. This demonstration showcases the structural optimization software's capability to handle both design and manufacturing aspects seamlessly. The approach to solving the structural optimization problem involves constructing a constrained parametric bell crank part in Abaqus/CAE as it facilitates easy manipulation of the geometry. The entire process of geometry generation, meshing, simulation, and output extraction was supported by developing Python scripts. Response surface model building and other statistical analyses are conducted using the JMP statistical software. Nonlinear constrained optimization is executed through the sequential quadratic programming (SLSQP solver) from the SciPy library, allowing optimization on the response surfaces representing the objective function and constraints to identify the optimal solution. The optimal solution is obtained utilizing a small composite design with individual response surface models for the objective function and each constraint, is compared with results from the Abaqus finite element model, and the percentage difference was 0.9% at the optimal design variable values. / Master of Science / Optimization processes, in general, require multiple iterations to converge to the optimal solution. Structural optimization, dealing with large and complex computationally intensive models are typically very time-consuming. To address this challenge, approximations of the actual design space, called response surfaces, are created using the statistical concept known as response surface methodology. Response surfaces are developed by selecting specific regions within the design space and studying them using complex computational models. The results obtained from these computational models are combined with statistical tools to build a response surface that approximately represents the actual design objective function and the associated constraints of the design within the specified design space. In this research, an adaptive approach called adaptive response surface optimization is implemented. In this approach, the regions studied and the response surfaces are dynamically adjusted based on the progression of the optimization process. Such adaptability significantly accelerates the structural optimization process and yields successful results. To illustrate this method, a benchmark problem was solved using the finite element solver Abaqus, the statistical software JMP, and the optimization toolbox from the Scipy library.
2

The Adaptive Response of Endothelial Cells to Shear Stress Alteration

Zhang, Ji January 2010 (has links)
<p>The adaptive response of vascular endothelial cells to shear stress alteration induced by global hemodynamic changes is an essential component of normal endothelial physiology in vivo; and an understanding of the transient regulation of endothelial phenotype during adaptation will advance our understanding of endothelial biology and yield new insights into the mechanism of atherogenesis. The objective of this study was to characterize the adaptive response of arterial endothelial cells to acute increases in shear stress magnitude and frequency in well-defined in vitro settings. Porcine endothelial cells were preconditioned by a basal level shear stress of ±15dynes/cm^2 at 1 Hz for 24 hours, and an acute increase in shear stress magnitude (30 ±15 dynes/cm^2) or frequency (2 Hz) was then applied. Endothelial permeability to bovine serum albumin was measured and gene expression profiling was performed using microarrays at multiple time points during a period of 6 hours after the shear stress alteration. The instantaneous endothelial permeability was found to increase rapidly in response to the acute increase in shear stress magnitude. Endothelial permeability nearly doubled after 40 minutes exposure to the elevated shear magnitude, and then decreased gradually. However, less dependency of endothelial permeability on shear stress frequency was observed. Endothelial permeability increased slowly from 120 minutes to 6 hours after exposure to the elevated shear frequency, but the increase was not statistically significant and was relatively small (1.2 fold increase at 6 hours). The transcriptomics studies identified 86 genes that were sensitive to the elevated shear magnitude and 37 genes sensitive to the elevated frequency. A significant number of the identified genes are previously unknown as sensitive to shear stress. The acute increase in shear magnitude promoted the expression of a group of anti-inflammatory and anti-oxidative genes; while the acute increase in shear frequency upregulated a set of cell-cycle regulating genes and angiogenesis genes. The adaptive response of global gene expression profile to the elevated shear magnitude is found to be triphasic, consisting of an induction period, an early adaptive response (ca. 45 minutes) and a late remodeling response. However, no apparent temporal regulation pattern of global gene expression was found during the adaptation to the elevated shear frequency. The results from this dissertation suggest that endothelial cells exhibit a specific phenotype during the adaptive response to changes in shear stress; and the transient phenotype is different than that of fully-adapted endothelial cells and may alter arterial atherosusceptibility.</p> / Dissertation
3

Envelope as Climate Negotiator: Evaluating adaptive building envelope's capacity to moderate indoor climate and energy

January 2013 (has links)
abstract: Through manipulation of adaptable opportunities available within a given environment, individuals become active participants in managing personal comfort requirements, by exercising control over their comfort without the assistance of mechanical heating and cooling systems. Similarly, continuous manipulation of a building skin's form, insulation, porosity, and transmissivity qualities exerts control over the energy exchanged between indoor and outdoor environments. This research uses four adaptive response variables in a modified software algorithm to explore an adaptive building skin's potential in reacting to environmental stimuli with the purpose of minimizing energy use without sacrificing occupant comfort. Results illustrate that significant energy savings can be realized with adaptive envelopes over static building envelopes even under extreme summer and winter climate conditions; that the magnitude of these savings are dependent on climate and orientation; and that occupant thermal comfort can be improved consistently over comfort levels achieved by optimized static building envelopes. The resulting adaptive envelope's unique climate-specific behavior could inform designers in creating an intelligent kinetic aesthetic that helps facilitate adaptability and resiliency in architecture. / Dissertation/Thesis / Ph.D. Environmental Design and Planning 2013
4

Étude de la réponse adaptative rénale et des mécanismes sous-jacents après exposition chronique à de faibles concentrations d'uranium ou de fluor / Study of the adaptive response in the kidney and the underlying mechanisms after chronic exposure to low doses of uranium and fluoride

Bontemps, Alice 09 December 2019 (has links)
L’uranium (U) et le fluor (F) sont des substances néphrotoxiques naturelles et anthropogéniques auxquelles la population peut être exposée quotidiennement. Cependant, leurs effets à faibles doses restent méconnus et des études précédentes suggèrent qu’une exposition chronique à de faibles doses pourrait induire une réponse adaptative (RA). Afin de mettre en évidence cette RA rénale in vivo, un protocole d’exposition prime à faibles doses suivie d’un traitement challenge néphrotoxique a été mis en place. Une première étude dose-réponse aiguë a permis de définir nos conditions challenge, avec des doses néphrotoxiques de 5 et 7.5 mg/kg d’U et de F, et un temps d’analyse de 72h post-injection. Pour l’étude de la RA, les souris ont été contaminées 6 mois via l’eau de boisson à des doses prime d’U (0, 10, 20 et 40 mg/L) ou de F (0, 15, 30 et 50 mg/L), puis traitées aux concentrations « challenge ». Une RA est observée aux doses respectives de 20 et 50 mg/L d’U et de F, avec un retour à la normale de l’expression et de la sécrétion de biomarqueurs de néphrotoxicité KIM-1 et CLU en comparaison aux animaux non pré-exposés. Une diminution de l’apoptose ou de l’expression in situ de VCAM est observée chez les animaux pré-exposés respectivement à 20 mg/L d’U ou à 50 mg/L de fluor, concentrations auxquelles la RA a été identifiée. L’autophagie, la réponse UPR et le recrutement de cellules inflammatoires sont des mécanismes induits par l’U alors que seule la réponse UPR est induite par le F. Cependant, nos résultats ne permettent pas de les identifier comme des mécanismes impliqués dans la RA, car ces derniers sont induits avec ou sans préexposition. En conclusion, cette étude montre l’existence d’une RA dans le cadre d’une exposition chronique à de faibles doses d’U ou de F chez la souris, avec l’induction de mécanismes adaptatifs tels que la régulation de l’apoptose et de l’inflammation. Ces résultats permettent de mieux appréhender les effets de faibles expositions chroniques chez l’Homme, et d’apporter de nouvelles connaissances pour la radioprotection de l’Homme. / Human population can be daily exposed to uranium (U) and fluoride (F) because of their natural and anthropogenic presence in the environment. Although U and F are known to be nephrotoxicant at high doses, their effects after low dose exposures are still unknown and previous studies suggested that chronic exposures to low doses of U or F could induce adaptive responses (AR). Therefore, a mouse in vivo study was designed and carried out to examine whether exposure to chronic low priming doses of U and F can induce AR in the kidney upon exposure to nephrotoxic challenge treatment. A pilot dose-response study allowed selecting the nephrotoxic challenge treatments (5 mg/kg U and 7.5 mg/kg F), with a time of analysis of 72h post treatment. To study the AR, mice were exposed through drinking water for 6 months to priming doses of U (10, 20 and 40 mg/L) or F (15, 30 and 50 mg/L), and subsequently challenged. An AR was observed at the doses of 20 mg/L U and 50 mg/L F, with a return to normal gene expression and urinary levels of nephrotoxicity biomarkers KIM 1 and CLU in comparison with the non-pre-exposed mice. Apoptosis was reduced in animals pre-exposed to 20 mg/L U and a decrease of VCAM in situ expression was observed in animals pre-exposed to 50 mg/L F. These concentrations correspond to the appearance of AR. The unfolded protein response (UPR), autophagy and inflammatory cell recruitment were the mechanisms induced by U whereas only UPR was induced by F. However, these mechanisms were induced in challenged animals irrespective of pre-exposure. Thus, our results do not allow us to identify these mechanisms as those involved in the AR. In summary, our data showed the existence of an AR to low doses of U and F delivered chronically to mice, with the induction of adaptive mechanisms such as apoptosis and inflammatory regulation. Results of this study allow for better understanding of the potential effects chronic low-dose exposures of U and F on human population, and provide new knowledge for informing the radioprotection system.
5

MODELING ANTI-CANCER DRUG RESISTANCE USING TUMOR SPHEROIDS

Shahi Thakuri, Pradip January 2019 (has links)
No description available.
6

IMMUNE SYSTEM MODULATION BY LOW DOSE IONIZING RADIATION

Dawood, Annum January 2021 (has links)
The historical narrative and our understanding about the low dose effects of radiation on the immune system has changed drastically from the beginning of the 20th century to now. A paradigm shift from the DNA target hit model to the one that also considers non-targeted effects (NTE) has attracted a lot of interest recently. Investigations to delineate mechanisms of NTE in the biological tissue have been carried out by various research groups where radiation induced genomic instability (RIGI), bystander effect (RIBE) and abscopal effect (AE) are the effects with most evidence available. This thesis addresses the question of whether low dose ionizing radiation (LDIR) stimulates or suppresses the immune system and how NTEs contribute to this immune modulation by adopting a two-pronged approach where first a narrative review constituting the introduction and literature review was performed followed by a systematic review using PRISMA guidelines to synthesize existing LDIR literature. This was prompted by our recent discovery that UVA photons are emitted by the irradiated cells and that these photons can trigger bystander effects in unirradiated recipients of these photons. Given the well-known association between UV radiation and the immune response, where these biphotons may pose as bystander signals potentiating processes in deep tissues as a consequence of ionising radiation, it is timely to revisit the field with a fresh lens. After reviewing various pathways and immune components that contribute to the beneficial and adverse effects induced by LDIR, it was found that these modulations can occur by way of NTE. However, the exact mechanistic underpinnings are still unclear and the literature examining low to medium dose effects of ionising radiation on the immune system is complex and controversial. Early work was compromised by lack of good dosimetry while later work mainly focuses on the involvement of immune responses in radiotherapy which typically uses high dose radiation. There is a lack of research in the LDIR/NTE field focussing on immune responses although bone marrow stem cells and lineages were critical in the identification and characterisation of NTE. This may be in part, a result of the difficulty of isolating NTE in whole organisms which are essential for good immune response studies. Models involving inter organism transmission of NTE are a promising route to overcome these issues. It is concluded that the simple question of whether LDIR stimulates or suppress the immune system is not as simple as initially hypothesized. An attempt was made to analyze if LDIR shifts the balance to immune suppression or enhancement via systematic review but, due to too many differences in the experimental methods in the current radiation and immune studies, a cookie-cutter answer was not possible. However, this thesis did point out the areas of concern such as lack of standardised tools in the field of radiobiological experimental research and quality of methods used which requires urgent attention. / Thesis / Master of Science (MSc)
7

The combined effects of thermal and radiological stress on the embryonic development of lake whitefish (Coregonus clupeaformis)

Kulesza, Adomas January 2017 (has links)
Lake whitefish (Coregonus clupeaformis; LWF) are a cold-adapted freshwater species that are of both economic and cultural value. These fish spawn in lake areas where their embryos are exposed to thermal power plant effluents that may contain low levels of thermal, radiological and chemical stressors. Many studies on LWF embryonic development have looked at the individual effects of these stressors, but few have looked at the potential for combined effects. The combined effects of thermal and radiological stress were of interest due to growing evidence that mild thermal stress can produce an adaptive response, through the induction of the heat shock response (HSR), when followed with subsequent ionizing radiation stress. This thesis examined the combined impacts of thermal and radiological stress during LWF embryogenesis. LWF embryos were exposed to mild heat shocks (HS; Δ3 or 9°C) prior to a high dose of acute 137Cs gamma rays at 2, 6 and 24 hours post heat shock during the gastrulation or eyed stage. Heat shocked embryos were collected at each developmental stage and assessed for induction of heat shock protein (Hsp) genes. Following exposure, embryos were raised until hatch where mortality, morphometry, and embryo weight were measured. Mild HS induced Hsp70 mRNA expression at gastrulation, but not at the eyed stage. Embryos at hatch were not impacted by thermal or radiological exposure at the gastrulation stage. During the eyed stage, acute radiation treatment increased mortality and decreased body size at hatch. Mild HS prior to radiation did not provide protective effects and no adaptive response was observed. This thesis better defines the combined effects of thermal and radiological stress on the embryonic development of LWF. It also suggests that the ontogeny aspects of heat shock responses and radiosensitivity are important to consider for future adaptive response studies. / Thesis / Master of Science (MSc)
8

The Cytochrome P450 2A5:Induction by Cadmium and its Role as Hepatic Bilirubin Oxidase

Abu Bakar, A'edah Unknown Date (has links)
Cadmium (Cd), is a non-essential metal with no known physiological function. It is known to alter redox state by disrupting the mitochondrial electron transport chain, as well as inactivating protein and non-protein thiols. It is thus believed that oxidative stress may comprise an important part of the mechanism of Cd toxicity. Accordingly, the initial cellular response to acute Cd exposure is defensive, where various anti-oxidant defence systems are triggered. One of the induced systems is the haem oxygenase-1 (HO-1). Its activation is mediated by the transcription factor Nrf2, which is the general regulator of cellular defence against oxidative stress. The protective effects of HO-1 are mediated, in part, through the generation of potent anti-oxidant bilirubin (BR) and its metabolites, which exploit the intrinsic antioxidant properties of these species at a cellular level. The oxidative metabolism of BR is an important route of detoxification in addition to glucuronidation. However, the major enzyme(s) involved in this oxidative degradation are not known. This thesis presents evidence for a major role of the hepatic cytochrome P450 2a5 (Cyp2a5) in BR degradation during Cd intoxication, where the BR levels are elevated following induction of HO-1. Treatment of DBA/2J male mice with CdCl2 induced both the Cyp2a5 and HO-1, and increased the microsomal BR degradation activity. By way of contrast, the total cytochrome P450 (CYP) content and the expression of Cyp1a2 were down-regulated by the treatment. The induction of the HO-1 and Cyp2a5 was significant at the mRNA, protein and enzyme activity levels. In each case, the up-regulation of the HO-1 preceded that of the Cyp2a5 with a 5-10 hr interval. In addition, BR totally inhibited the microsomal coumarin hydroxylase activity (a Cyp2a5-catalysed reaction) with an IC50 approximately equal to the substrate concentration. The MROD activity, catalysed mainly by the Cyp1a2, was inhibited up to 36% by BR. The microsomal BR degradation was inhibited by coumarin and by a monoclonal antibody against the Cyp2a5 by about 90%. In addition, 7-methoxyresorufin, a substrate for Cyp1a2, inhibited BR degradation activity by approximately 20%. A study using Nrf2 null mutant mice suggests that Cd-mediated induction of Cyp2a5 is dependent on the transcription factor Nrf2. Additionally, acute exposure to Cd activated localisation of Nrf2 from the cytoplasm to the nucleus. Furthermore, electrophoretic mobility shift assay (EMSA) analysis suggests that Cd induced sequence-specific binding of various species of the StRE-binding proteins on the 5’-flanking region of the Cyp2a5 gene. Collectively, these observations strongly suggest that BR may act as a substrate for the hepatic Cyp2a5, a major catalyst for BR degradation under conditions of substantial elevation of BR levels following induction of HO-1 by Cd. Secondly, the concurrent up-regulation of the HO-1 and Cyp2a5 during Cd-mediated injury implicates a coordinated regulation of two enzyme systems in the maintenance of balancing BR production and elimination. Finally, StRE-binding proteins, in particular Nrf2, may be involved in the regulation of the Cyp2a5 gene, which leads to the oxidation of BR. However, the respective roles of these factors in the regulation of the Cyp2a5 gene, as well as the coordinated regulation of ho-1 and Cyp2a5 genes remain an open question, requiring further investigations.
9

Resposta adaptativa e efeitos das substâncias oxidantes - K2TeO3, H2O2 e paraquate - na produção de biofilme de amostras de Corynebacterium diphtheriae isolados de origens diversas / Adaptative response and effects of oxidizing substances - K2TeO3, H2O2 and paraquat the production of biofilm samples of Corynebacterium diphtheria isolated from different sources

Aparecido Donizeti Teixeira 27 March 2013 (has links)
A difteria é uma doença imunoprevinível que permanece endêmica em diversas regiões do mundo. Além dos casos de difteria clássica, doenças invasivas como endocardite, osteomielite, pneumonia e infecções relacionadas à cateter, tem acometido indivíduos adultos parcialmente imunizados. A natureza multifatorial dos fatores de virulência que favorecem a formação de biofilme e sobrevivência em macrófagos tem sido evidenciada para o Corynebacterium diphtheriae. Entretanto, escassos são os trabalhos que investigaram a influência de condições ambientais na virulência do patógeno. Uma vez que agentes oxidantes são capazes de gerar radicais livres e levar ao estresse oxidativo que, consequentemente, podem resultar em resposta adaptativa e influenciar na formação do biofilme e na virulência bacteriana, o presente trabalho teve como objetivo geral avaliar os efeitos do peróxido de hidrogênio (H2O2), paraquate e telurito de potássio (K2TeO3) em propriedades biológicas de cepas de C. diphtheriae de origens diversas. Os resultados demonstraram que as amostras de C. diphtheriae apresentaram níveis de resistência ao K2TeO3, H2O2 e paraquate, porém em intensidades variadas e independentes da capacidade de produção da toxina diftérica. Algumas amostras, toxinogênicas ou não, isoladas do trato respiratório superior demonstraram resposta adaptativa para H2O2 passando, portanto, a expressar resistência aumentada após uma prévia exposição ao referido agente oxidante. C. diphtheriae não exibiu respostas adaptativas para o K2TeO3 e paraquate. C. diphtheriae foi capaz de produzir biofilme na superfície de substratos abióticos de natureza hidrofílica (vidro) e hidrofóbica (poliestireno) na presença de agentes oxidantes K2TeO3, H2O2 e paraquate. A presença dos agentes oxidantes influenciou na formação de biofilme de algumas amostras. O paraquate inibiu a produção de biofilme de todas amostras. A amostra TR241 teve a produçao de biofilme inibida na presença dos três agentes oxidantes analisados. Por outro lado, a presença de H2O2 e do K2TeO3 estimulou a produção de biofilme de algumas amostras. Para todas as amostras de C. diphtheriae testadas, independentes das origens, biotipos e da capacidade de produção de toxina diftérica, os ensaios moleculares indicaram a presença de sequências gênicas cromossômicas homólogas, codificadores da proteína DIP 0906 (TeR) e da proteína DIP 1421 (OxyR), envolvidos na resistência ao telurito e na proteção contra o estresse oxidativo, respectivamente. Não foi observada correlação da suscetibilidade e a resposta adaptativa aos agentes oxidantes com as diferentes características bacterianas: origem, sítio de isolamento, produção de toxina diftérica, metabolização de sacarose e produção de biofilme. Em conclusão, o estresse oxidativo foi capaz de influenciar fatores de virulência do C. diphtheriae, como a capacidade de produçao de biofilme, que podem estar contribuindo para a patogenia da difteria clássica assim como de doenças invasivas causadas por cepas atoxinogênicas. / Diphtheria is a disease it could be preventable by immunization although remains endemic in many regions of the world. Besides the classical cases of diphtheria, invasive diseases such as endocarditis, osteomyelitis, pneumonia and catheter-related infections, has affected adults partially immunized. The multifactorial nature of virulence factors that promote biofilm formation and survival in macrophages have been shown to Corynebacterium diphtheriae. However, few are the studies that investigated the influence of environmental conditions on the virulence of the pathogen. Since oxidants are capable of generating free radicals lead to oxidative stress and, consequently, may result in adaptive response and influence in biofilm formation and bacterial virulence, this study aimed to evaluate the effects of hydrogen peroxide (H2O2), paraquat and potassium tellurite (K2TeO3) in biological properties of strains of C. diphtheriae of different origins. The results show that the strains of C. diphtheriae showed levels of resistance K2TeO3, H2O2 and paraquat, but in varying intensities and independent production capacity of diphtheria toxin. Some samples, toxigenic or non-toxigenic, isolated respiratory tract demonstrated adaptive response to H2O2 passing thus expressing increased resistance after exposure prior to said oxidizing agent. C. diphtheriae seemed not display adaptive responses to K2TeO3 and paraquat. C. diphtheriae was able to produce biofilm on the surface of substrates abiotic hydrophilic in nature (glass) and hydrophobic (polystyrene) in the presence of oxidizing agents - K2TeO3, H2O2 and paraquat. The presence of oxidizing agents influence the biofilm formation of some samples.The paraquat inhibited the production of biofilm from all samples. The sample TR241 had inhibited the production of biofilm in the presence of oxidizing agents three analyzed. Moreover, the presence of H2O2 and K2TeO3 stimulated biofilm production of some samples. For all samples C. diphtheriae tested, independent of the origins and biotypes production capacity of diphtheria toxin, molecular assays indicated the presence of chromosomal gene sequences homologous to genes involved in tellurite resistance and protection against oxidative stress present in other bacterial species, genes encoding protein DIP 0906 (Ter) and protein DIP 1421 (oxyR). No correlation was observed susceptibility and adaptive response to oxidants with different biological activities bacterial: origin, isolation site, production of diphtheria toxin, sucrose metabolism and biofilm production. In conclusion, oxidative stress was able to influence virulence factors of C. diphtheriae, as the capacity of production of biofilm, which may be contributing to the pathogenesis of diphtheria classical as well as invasive disease caused by strains non-toxigenic.
10

Resposta adaptativa e efeitos das substâncias oxidantes - K2TeO3, H2O2 e paraquate - na produção de biofilme de amostras de Corynebacterium diphtheriae isolados de origens diversas / Adaptative response and effects of oxidizing substances - K2TeO3, H2O2 and paraquat the production of biofilm samples of Corynebacterium diphtheria isolated from different sources

Aparecido Donizeti Teixeira 27 March 2013 (has links)
A difteria é uma doença imunoprevinível que permanece endêmica em diversas regiões do mundo. Além dos casos de difteria clássica, doenças invasivas como endocardite, osteomielite, pneumonia e infecções relacionadas à cateter, tem acometido indivíduos adultos parcialmente imunizados. A natureza multifatorial dos fatores de virulência que favorecem a formação de biofilme e sobrevivência em macrófagos tem sido evidenciada para o Corynebacterium diphtheriae. Entretanto, escassos são os trabalhos que investigaram a influência de condições ambientais na virulência do patógeno. Uma vez que agentes oxidantes são capazes de gerar radicais livres e levar ao estresse oxidativo que, consequentemente, podem resultar em resposta adaptativa e influenciar na formação do biofilme e na virulência bacteriana, o presente trabalho teve como objetivo geral avaliar os efeitos do peróxido de hidrogênio (H2O2), paraquate e telurito de potássio (K2TeO3) em propriedades biológicas de cepas de C. diphtheriae de origens diversas. Os resultados demonstraram que as amostras de C. diphtheriae apresentaram níveis de resistência ao K2TeO3, H2O2 e paraquate, porém em intensidades variadas e independentes da capacidade de produção da toxina diftérica. Algumas amostras, toxinogênicas ou não, isoladas do trato respiratório superior demonstraram resposta adaptativa para H2O2 passando, portanto, a expressar resistência aumentada após uma prévia exposição ao referido agente oxidante. C. diphtheriae não exibiu respostas adaptativas para o K2TeO3 e paraquate. C. diphtheriae foi capaz de produzir biofilme na superfície de substratos abióticos de natureza hidrofílica (vidro) e hidrofóbica (poliestireno) na presença de agentes oxidantes K2TeO3, H2O2 e paraquate. A presença dos agentes oxidantes influenciou na formação de biofilme de algumas amostras. O paraquate inibiu a produção de biofilme de todas amostras. A amostra TR241 teve a produçao de biofilme inibida na presença dos três agentes oxidantes analisados. Por outro lado, a presença de H2O2 e do K2TeO3 estimulou a produção de biofilme de algumas amostras. Para todas as amostras de C. diphtheriae testadas, independentes das origens, biotipos e da capacidade de produção de toxina diftérica, os ensaios moleculares indicaram a presença de sequências gênicas cromossômicas homólogas, codificadores da proteína DIP 0906 (TeR) e da proteína DIP 1421 (OxyR), envolvidos na resistência ao telurito e na proteção contra o estresse oxidativo, respectivamente. Não foi observada correlação da suscetibilidade e a resposta adaptativa aos agentes oxidantes com as diferentes características bacterianas: origem, sítio de isolamento, produção de toxina diftérica, metabolização de sacarose e produção de biofilme. Em conclusão, o estresse oxidativo foi capaz de influenciar fatores de virulência do C. diphtheriae, como a capacidade de produçao de biofilme, que podem estar contribuindo para a patogenia da difteria clássica assim como de doenças invasivas causadas por cepas atoxinogênicas. / Diphtheria is a disease it could be preventable by immunization although remains endemic in many regions of the world. Besides the classical cases of diphtheria, invasive diseases such as endocarditis, osteomyelitis, pneumonia and catheter-related infections, has affected adults partially immunized. The multifactorial nature of virulence factors that promote biofilm formation and survival in macrophages have been shown to Corynebacterium diphtheriae. However, few are the studies that investigated the influence of environmental conditions on the virulence of the pathogen. Since oxidants are capable of generating free radicals lead to oxidative stress and, consequently, may result in adaptive response and influence in biofilm formation and bacterial virulence, this study aimed to evaluate the effects of hydrogen peroxide (H2O2), paraquat and potassium tellurite (K2TeO3) in biological properties of strains of C. diphtheriae of different origins. The results show that the strains of C. diphtheriae showed levels of resistance K2TeO3, H2O2 and paraquat, but in varying intensities and independent production capacity of diphtheria toxin. Some samples, toxigenic or non-toxigenic, isolated respiratory tract demonstrated adaptive response to H2O2 passing thus expressing increased resistance after exposure prior to said oxidizing agent. C. diphtheriae seemed not display adaptive responses to K2TeO3 and paraquat. C. diphtheriae was able to produce biofilm on the surface of substrates abiotic hydrophilic in nature (glass) and hydrophobic (polystyrene) in the presence of oxidizing agents - K2TeO3, H2O2 and paraquat. The presence of oxidizing agents influence the biofilm formation of some samples.The paraquat inhibited the production of biofilm from all samples. The sample TR241 had inhibited the production of biofilm in the presence of oxidizing agents three analyzed. Moreover, the presence of H2O2 and K2TeO3 stimulated biofilm production of some samples. For all samples C. diphtheriae tested, independent of the origins and biotypes production capacity of diphtheria toxin, molecular assays indicated the presence of chromosomal gene sequences homologous to genes involved in tellurite resistance and protection against oxidative stress present in other bacterial species, genes encoding protein DIP 0906 (Ter) and protein DIP 1421 (oxyR). No correlation was observed susceptibility and adaptive response to oxidants with different biological activities bacterial: origin, isolation site, production of diphtheria toxin, sucrose metabolism and biofilm production. In conclusion, oxidative stress was able to influence virulence factors of C. diphtheriae, as the capacity of production of biofilm, which may be contributing to the pathogenesis of diphtheria classical as well as invasive disease caused by strains non-toxigenic.

Page generated in 0.0876 seconds