Dissertations / Theses on the topic 'Uremic toxin'
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Bollinger, Laurie M. "Factors affecting prevalence of Shiga toxin-producing Escherichia coli in cattle /." abstract and full text PDF (UNR users only), 2008. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3329564.
Full textMorigi, Marina. "Unravelling molecular and biochemical dysfunction by Shiga toxin: implication for thrombotic microangiopathy in Hemolytic Uremic Syndrome." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 2006. http://arno.unimaas.nl/show.cgi?fid=7590.
Full textKarpman, Diana O. "Studies of the pathogenesis of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura." Lund : Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/68945090.html.
Full textLeeper, Molly Maitland. "Trends in Toxin Profiles of Human Shiga Toxin-Producing Escherichia Coli (STEC) O157 Strains, United States, 1996-2008." Atlanta, Ga. : Georgia State University, 2009. http://digitalarchive.gsu.edu/iph_theses/57/.
Full textTitle from file title page (Digital Archive@GSU, viewed June 16, 2010) Karen Giseker, committee chair; Peter Gerner-Smidt, committee member. Includes bibliographical references (p. 101-105).
Gomes, Priscila Aparecida Dal Pozo. "Desenvolvimento de uma nova estratégia vacinal contra síndrome hemolítica urêmica utilizando linhagens geneticamente modificadas de Bacillus subtilis capazes de expressar a toxina Stx2 de EHEC." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/42/42132/tde-04062008-102629/.
Full textThe Hemolytic Uremic Syndrome (HUS) is the main disease associated with infections with Shiga toxin (Stx) - producing Escherichia coli strain and no effective vaccine or treatment exist. The Stx toxin consist of an enzymatically active A subunit and a pentameric B subunit responsible toxin binding to host cells. In this work we propose the use of Bacillus subtilis, a harmless spore form bacteria as a vaccine vehicle for the expression atoxic forms of Stx2, under the control of stress inducible (PgsiB) promoter. BALB/c mice immunized with vegetative cells and spores of the B. subtilis vaccine strain using different immunization routes elicited low specific antibody levels at serum (IgG) or fecal extracts (IgA). We also investigated the immunogenic potencial of StxB purified from recombinant E. coli strain, but the induced anti-StxB antibodies did not neutralize the native toxin. The results indicate that alternative expression system or the incorporation of the adjuvants are required for the generation of vaccine formulation active against HUS.
McGannon, Colleen M. "Antibiotic Therapy in the Treatment of E. coli O157:H7." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1230919332.
Full textFogo, Verônica Simões. "Prevalência e caracterização de Escherichia coli O157:H7 e outras cepas produtoras de toxina de Shiga (STEC) na linha de abate de carne bovina destinada à exportação." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/9/9131/tde-27012017-123850/.
Full textEscherichia coli is a microorganism present in the intestinal tract of humans and warm-blood animals, being part of the normal microbiota and harmless to the host. However, some strains are able to cause human and animal infections. Shiga toxin-producing E. coli (STEC), regarded as foodborne pathogens, can cause since mild or severe and bloody diarrhea to major complications, such as hemorrhagic colitis (HC), hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Cattle are considered the main reservoir of this pathogen and the transmission to humans happens, most of the times, due to the consumption of contaminated food or water. The aim of the present research was to determine the prevalence of E. coli O157:H7 and other STEC on hide samples of beef cattle and on their corresponding carcasses, sampled prior to evisceration, and half-carcasses, sampled after evisceration; identity the genes that code for the virulence factors (stx1, stx2, eaeA e ehxA) of the isolates; detect E. coli O157:H7 strains using the gene uidA as epidemiological marker; identify the serotypes of the STEC isolates; verify the citotoxicity of the isolates in Vero cells and evaluate their resistance to different antibiotics. From 198 animals sampled, seven (3.5%) carried STEC strains. In six (3%) of them, STEC was detected on hide and in one (0.5%) it was isolated from half-carcass. The 23 strains isolated from hide presented the profile stx2, eaeA, uidA e ehxA, and were regarded as enterohemorrhagic Escherichia coli (EHEC), and the one isolated from half-carcass presented the profile stx2, uidA e ehxA. From the 24 isolated strains, 13 (54.2%) belonged to the serotype O157:H7. Besides this serotype, other strains belonging to serotypes that have been previously described and associated with severe human infections in Brazil and other countries, such as O174:H21 , O6:H49, ONT:H7, ONT:H8 and OR:H10, were isolated. From seven animals with strains harboring stx2, and ehxA, five (71.4%) presented verocytotoxigenic strains and one (14.2%) presented enterohemolisin producing strains. Regarding the antibiotics tested, four (16.7%) of the 24 isolated strains were resistant to some antibiotic, being three (12.5%) to streptomycin and one (4.2%) to streptomycin and ampicilin. Faced with these results, the production of enterohemolisin and the search of the genes ehxA and uidA can not be considered good epidemiological markers for the serotype O157:H7. The isolation of STEC strain from the half-carcass alerts for the need of surveillance on the presence of these microorganisms, since they may contaminate the final product, representing a risk to consumers health.
ASTORI, EMANUELA. "IN VITRO AND IN VIVO APPROACHES TO STUDY OXIDATIVE STRESS, ANEMIA AND DYSBIOSIS IN CHRONIC KIDNEY DISEASE." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/818976.
Full textLoganathan, Narasimhan. "Adsorption of protein bound uremic toxins in zeolites : a molecular simulation study." Aix-Marseille 1, 2010. http://www.theses.fr/2010AIX11120.
Full textThe paracresol as a free molecule is a uremic toxin that may cause critical cell damages which can eventually lead to heart failures. The treatment of renal insufficiency is essentially based on the utilisation of the dialysis techniques. However, it appears that, this process does not allow the effective elimination of the molecule. A possible alternative would be to use zeolites to sequestrate the molecule in order to eliminate it. This PhD thesis presents a theoretical investigation of the adsorption of paracresol and water in the silicalite-1 and faujasite NaX and NaY zeolites. The computer simulations were performed using the Monte Carlo technique in both the grand-canonical and canonical ensembles at a temperature of 98. 6° (310 K). The results show that, a cooperative effect could appear between both molecules during the coadsorption in silicalite-1. The detailed study of the energetic intermolecular interactions seems to confirm this hypothesis. The simulations show that, the mechanism of adsorption in the faujasite zeolites is somewhat different
Yi, Dan. "Contribution to the study of uremic toxins in the context of chronic kidney disease." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEI054.
Full textChronic kidney disease (CKD) is a condition characterized by progressive loss of kidney function. CKD is associated with the accumulation of various uremic toxins. Uremic toxins or uremic retention solutes are compounds that accumulate in patients with CKD due to impaired renal clearance and exert deleterious biological effects. Protein-bound uremic toxins (PBUT) is poorly removed by hemodialysis because of its binding to plasma proteins, particularly human serum albumin. As a result, protein-bound uremic toxins accumulate in patients with CKD and their concentration can hardly be reduced in patients with end-stage renal disease (ESRD). My work focuses mainly on uremic toxins, particularly protein-bound uremic toxins such as indoxyl-sulfate (IS), phenylacetic acid (PAA) and p-cresyl-glucuronide (p-CG); and zinc-alpha2-glycoprotein (ZAG) which is a "middle molecule". We investigated the role of IS in the development of insulin resistance and other metabolic disorders associated with CKD, as well as its effects on inflammation and oxidative stress. We have investigated the binding properties of PAA and p-CG to serum albumin, which is the most abundant protein in human plasma. Finally, we tried to develop a new strategy to eliminate PBUTs, using chemical displacers / competitors
Hussain, Mohamed Siyab Eldin Elsadig Ahmed [Verfasser], and F. [Akademischer Betreuer] Lang. "Induction of eryptosis by uremic toxins / Mohamed Siyab Eldin Elsadig Ahmed Hussain ; Betreuer: F. Lang." Tübingen : Universitätsbibliothek Tübingen, 2013. http://d-nb.info/1160684499/34.
Full textRoche, Iain. "Nanoporous polymeric adsorbents for blood purification." Thesis, Loughborough University, 2009. https://dspace.lboro.ac.uk/2134/8143.
Full textRodrigues, Gabriela Gomes Cardoso. "Efeito da toxina urêmica indoxil sulfato em cultura de mioblastos c2c12 tratados ou não com laser de baixa potência." Universidade Nove de Julho, 2015. http://bibliotecadigital.uninove.br/handle/tede/1298.
Full textMade available in DSpace on 2016-05-17T20:42:43Z (GMT). No. of bitstreams: 1 Gabriela Gomes Cardoso Rodrigues.pdf: 623885 bytes, checksum: 3da3d1230fd77beffc9c12f00be889bb (MD5) Previous issue date: 2015-02-04
Chronic kidney disease (CKD) is characterized by progressive and irreversible loss of renal function and often progresses with a muscular weakness, whose set of signs and symptoms is generally referred to as uremic myopathy. Possible risk factors for the uremic myopathy are the uremic toxins. Among uremic toxins, indoxyl sulfate (IS) is a derivative of tryptophan metabolism by intestinal bacteria. Because skeletal muscle tissue undergo constant remodeling due differentiation of myoblasts in myotubes, it is possible that uremic toxins have a deleterious effect to influence this process, exacerbating the uremic myopathy. Low level laser therapy (LLLT) is regarded as a growth promoter feature widely used in the treatment of chronic diseases and has shown positive effects on the modulation of skeletal muscle repair process and also in the process of inflammation. However, in the context of CKD, the LLLT has not yet been explored. The aim of this study was to evaluate the effects of the IS on cell viability and on oxidative stress on cellular differentiation in cultured C2C12 myoblasts. In addition, to verify the action of the LLLT as a protective alternative to the cells. The C2C12 myoblasts were cultured in DMEM culture medium containing 10% fetal bovine serum and were induced to differentiation process by adding 2% horse serum. Three different IS concentrations were used to mimic the plasma concentrations of normal individual, CKD patients with moderate uremia and CKD patients with advanced uremia (0.6 mg/l and 53 mg/l and 236 mg/l, respectively), at different times of incubation (24 h, 48 h and 72 h). Subsequently, the cells were subjected to treatment with LLLT GaAlAs 780 nm (output power 10 mW, 20 seconds application time and energy density of 0.5 J / cm2). In terms of analysis, we used MTT method to assess the viability of the cells, flow cytometry to assess the viability/cell death and oxidative stress, nitrite dosing to evaluate nitric oxide production and real-time PCR to analyze IL-6, myogenin and MyoD expression (inflammation and cell differentiation markers). The results demonstrate that the IS at the maximum concentration was toxic to C2C12 cells, because it significantly decreased cell viability by MTT and by flow cytometry and by increasing the percentage of necrosis. This effect was present throughout the three incubation periods. With respect to oxidative stress, was not any conclusion, probably by the time the samples, but do not rule out the possibility of IS induce this type of stress. Although the IS has induced death to C2C12 cells, the remaining had no change in cell differentiation markers. Treatment with BPL the IS sensitized cells, reducing cell viability. We conclude that the IS acts directly on C2C12 myoblasts with toxic effect and may be the one factor responsible for uremic myopathy. Treatment with LLLT was not effective in protecting the cells.
A doença renal crônica (DRC) é caracterizada pela perda progressiva e irreversível da função renal e que frequentemente cursa com um quadro de fraqueza muscular, cujo conjunto de sinais e sintomas é globalmente designado como miopatia urêmica. Possíveis fatores predisponentes para a miopatia urêmica são as toxinas urêmicas. Dentre as toxinas urêmicas, o indoxil sulfato (IS) é uma derivada do metabolismo do triptofano presente em bactérias intestinais. Devido ao fato do tecido muscular esquelético sofrer constante remodelação graças à diferenciação de mioblastos em miotubos, é possível que toxinas urêmicas tenham um efeito deletério por influenciar este processo, agravando a miopatia urêmica. A terapia a laser de baixa potência (LBP) é considerada como um recurso bioestimulante amplamente utilizado no tratamento de doenças crônicas e tem demonstrado efeitos positivos sobre a modulação do processo de reparo muscular esquelético e também no processo da inflamação. Entretanto, no contexto de DRC, o LBP não foi ainda explorado. O objetivo do presente estudo foi avaliar dos efeitos do IS sobre a viabilidade celular, sobre o estresse oxidativo e sobre a diferenciação celular em cultura de mioblastos C2C12. Além disso, verificar a ação do LBP como forma de proteção às células. Os mioblastos C2C12 foram cultivados em meio de cultura de DMEM, contendo 10% de soro fetal bovino e foram induzidos ao processo de diferenciação por meio da adição de 2% soro de cavalo. Três diferentes concentrações de IS foram usadas para mimetizar as concentrações plasmáticas de indivíduo normal, paciente DRC com uremia moderada e paciente DRC com uremia avançada (0,6 mg/l; 53 mg/l e 236 mg/l, respectivamente), em diferentes períodos de incubação (24 h, 48 h e 72 h). Posteriormente, as células foram submetidas ao tratamento com laser de baixa potência AsGaAl 780 nm (potência de saída de 10 mW, tempo de aplicação de 20 segundos e densidade de energia de 0,5 J/cm2). Como análise, foi utilizado o método MTT para acessar a viabilidade das células, citometria de fluxo para avaliar a viabilidade/mortalidade das células, bem como o estresse oxidativo, dosagem de nitrito para avaliar a produção de óxido nítrico e PCR em tempo real para analisar a expressão de IL-6, miogenina e MyoD (marcadores de inflamação e diferenciação celular). Os resultados demonstram que o IS na concentração máxima foi tóxico para as células C2C12, pois diminuiu significativamente a viabilidade das células, tanto por MTT como por citometria de fluxo, aumentando a porcentagem de necrose. Este efeito foi presente nos três períodos de incubação. Com relação ao estresse oxidativo, não foi possível nenhuma conclusão, provavelmente pelo tempo das amostras , porém não descartamos a possibilidade do IS induzir este tipo de estresse. Embora o IS tenha induzido morte às células C2C12, as remanescentes não tiveram alteração dos marcadores de diferenciação celular. O tratamento com LBP sensibilizou as células ao IS, diminuindo a viabilidade das células. Concluímos que o IS age diretamente sobre mioblastos C2C12 com efeito tóxico, podendo ser um dos responsáveis pela miopatia urêmica. O tratamento com LBP não foi eficiente na indução de proteção às células.
Gallice, Philippe. "Toxines uremiques : leur role dans l'inhibition de la pompe a sodium chez les patients insuffisants renaux chroniques traites par hemodialyse." Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX22952.
Full textDevine, Eric [Verfasser], and Detlef H. [Akademischer Betreuer] Krieter. "Increased removal of protein bound uremic toxins through reversible modification of the ionic strength during hemodiafiltration / Eric Devine. Betreuer: Detlef H. Krieter." Würzburg : Universitätsbibliothek der Universität Würzburg, 2013. http://d-nb.info/1043906606/34.
Full textPanahi, Tayyebeh. "Glutamic Acid Resorcinarene-based Molecules and Their Application in Developing New Stationary Phases in Ion Chromatography." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6436.
Full textGuichard-Koppe, Laetitia. "Rôle d'une toxine urémique, le p-cresyl sulfate dans l'insulinorésistance associée à la maladie rénale chronique." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10097.
Full textAlthough insulin resistance is a well-documented feature of chronic kidney disease (CKD), the underlying mechanisms remain poorly understood. p-cresol is a toxic by product generated by transformation of tyrosine by intestinal microbiota. Its conjugate p-cresyl sulfate (PCS) is identified as the main circulating metabolite of p-cresol and a major protein bound uremic toxin. PCS is independently associated with mortality and cardiovascular disease in CKD patients. The aim of this study was to determine the role of PCS in CKD-associated insulin-resistance. Chronic administration of PCS (10mg/kg, twice daily for 4 weeks) in mice with normal kidney function triggered insulin resistance, fat mass loss and ectopic lipid redistribution in muscle and liver (lipotoxicity) mimicking those associated to CKD. PCS mice revealed altered insulin signaling in skeletal muscle through ERK1/2 activation. Exposition of C2C12 myotubes to PCS at CKD-relevant concentrations (40 μg/ml) caused insulin resistance, also through a direct activation of ERK1/2. Mouse models of surgically induced renal failure displayed insulin resistance and dyslipidemia, and treatment with a prebiotic (arabino-xylo-oligosaccharide) reducing p-cresol intestinal production and thus serum PCS, prevented these metabolic defects. These data suggest that although PCS is poorly removed by the common dialysis techniques, alternative therapeutic such prebiotics ttargeting of PCS may prevent metabolic abnormalities associated to end-stage renal disease
Sheremet, Andriy. "Bioinspired polyethersulfone-based hollow fiber membranes as the scaffolds in renal assist device for protein-bound toxins removal from blood." Master's thesis, Faculdade de Ciências e Tecnologia, 2014. http://hdl.handle.net/10362/13308.
Full textErasmus Mundus Master in Membrane Engineering
Using bioartificial kidney is the promising approach for removal of non-dializable, proteinbound uremic toxins, which are responsible for high mortality and morbidity in treating kidney failure related conditions. Additionaly, bioartificial kidney device could perform the physiological roles of the kidney such as metabolic replacement, endocrine function and immunomodulation. In the current work two commercial polyethersulfone-based membranes, Gambro HCO 1100 and Membrana MicroPES TF10 used in haemofiltration and plasma separation applications respectively were investigated. To provide adequate cytocompatibility of the membrane biomimetic, biomimetic double layer coating was developed. First, the membranes were coated with musselinspired synthetic polydopamine film, following with the coating of Collagen Type IV. Transport properties of the coated and native membranes were investigated. Increase in pure water permeability of the coated HCO 1100 membranes was observed. Membrane surface hydrophilization was assumed as the major factor responsible for the effect. Membrane permeabilities for bovine serum albumin and immunoglobulin G solutions were studied. Significant increase in protein rejection was observed for double coated HCO 1100 membranes with small or no effect of the double coated MicroPES TF10 membranes. Next, formation of confluent monolayers of the renal epithelial cells on the membrane scaffolds was studied. Cell seeding strategy was developed and two seeding conditions were tested. Specifically, the cells were allowed to adhere to the biomimetic membranes passively, and the negative pressure was applied to facilitate cell adhesion. After cultivation in semi-batch conditions the monolayer formation was examined. Confluent monolayers were observed for the conditions with passive cell adherence for the both membranes. Cell contacts formation and cell polarization were confirmed with the staining for ZO-1 protein. Applying the pressure to facilitate cell adhesion, on the contrary, resulted in the loss of cell ability to form functional monolayers.
EM3E Master is an Education Programme supported by the European Commission, the European Membrane Society (EMS), the European Membrane House (EMH), and a large international network of industrial companies, research centres and universities
Mallick, Emily M. "A New Murine Model For Enterohemorrhagic Escherichia coli Infection Reveals That Actin Pedestal Formation Facilitates Mucosal Colonization and Lethal Disease: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/601.
Full textEbah, Leonard. "Extraction and analysis of interstitial fluid, and characterisation of the interstitial compartment in kidney disease." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/extraction-and-analysis-of-interstitial-fluid-and-characterisation-of-the-interstitial-compartment-in-kidney-disease(8e9ce4a2-8ec4-41ee-ac22-bc142ca9e0b0).html.
Full textHoibian, Elsa. "Impact de l'insuffisance rénale chronique et de l'urémie sur la motilité et la perméabilité intestinale." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEI066.
Full textChronic Kidney Disease (CKD) result from a progressive kidney dysfunction. CKD is associated with an increase in the concentration of uremic toxins inducing CKD-associated metabolic alterations. Our work focused on the impact of renal dysfunction on gut permeability and gut motility. In vivo, CKD was induced in mice by chemical nephrectomy (adenine-enriched diet); In vitro, Caco-2 cells were incubated for 24h with 10% (v/v) of uremic plasma to mimic the uremic environment. Gastrointestinal transit time, gut motility, intestinal permeability and expression of tight junction proteins were explored. In vivo, kidney failure was associated with an impaired gastrointestinal transit and an increased intestinal permeability associated with a dysregulation of tight junction proteins (mainly claudine-1 overexpression). The Caco-2 monolayer permeability was significantly increased in cell monolayers incubated with uremic plasma. Claudine-1 expression and abundance was increased. In CKD, gut motility and gut permeability (e.g. « leaky » gut) are significantly impaired. Generally speaking, these gut dysfunctions could promote the production and the absorption of uremic toxins contributing to the uremic syndrom
Santos, Diego Borba dos. "Desenvolvimento de método analítico para a determinação simultânea de para-cresol e compostos guanidínicos em plasma de cães." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/75/75135/tde-06052015-152108/.
Full textPara-cresol (4-methylphenol) and guanidino compounds are involved in a series of biochemical and physiological cycles. Under ordinary conditions, these compounds are excreted from the body by healthy kidneys. However, in uremic patients, the concentration of these compounds is highly increased in biological fluids and tissues and is of hard removal, increasing the mortality rate in dialysis patients. Gas chromatography (GC) and high performance liquid chromatography (HPLC) are the most used techniques for separation and quantification of p-cresol and guanidino compounds. For the guanidines determination, derivatizing reactions are usually employed to enhance the absorbance, fluorescence or volatility of these compounds, allowing the quantification. Ninhydrin is one of the most used reagents for derivatization because it shows high sensitivity and presents water solubility. The procedure employed for the derivatization reaction is simple, allowing the automation of sample preparation system, when it is required. There are few studies quantifying the concentration of guanidino compounds and p-cresol in blood of uremic dogs, therefore, a better understanding of the role of these compounds in the metabolism of dogs are needed. For this reason, it is important to develop an analytical method for the quantification of these compounds in dog\'s blood. The development of a method for simultaneous determination of these compounds, which is not reported in the literature, can improve the analytical productivity, decreasing the time spent with sample preparation and analysis. Here, a method based in reversed-phase HPLC for simultaneous quantification of guanidino compounds and free p-cresol in plasma of uremic dogs with fluorescence detection was developed, validated and applied. For this purpose, the ninhydrin derivatization reaction was reviewed, characterized by mass spectrometry (MS) and optimized using central composite design (CCD). A total of 63 samples of dog plasma, including healthy and uremic groups, were analyzed. The mean concentration of guanidine, methylguanidine and free p-cresol determined by the validated method, for the uremic group, were higher than the healthy group, alike usual for humans, suggesting a similar metabolic behavior of these compounds in dogs. The obtained method is relatively simple avoiding complex sample preparation and the experimentally designed optimization of the ninhydrin reaction by CCD yielded a gain of area as high as 1000% for the chromatographic peaks.
Cheddani, Lynda. "Comparaison du risque cardiovasculaire et de la mortalité entre patients transplantés rénaux et malades rénaux chroniques à fonction rénale équivalente. Uremic Toxins and Clinical Outcomes: The Impact of Kidney Transplantation Higher mortality risk among kidney transplant recipients than among estimated glomerular filtration rate-matched patients with CKD – preliminary results Less arterial stiffness in kidney transplant recipients than chronic kidney disease patients matched for renal function." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASR006.
Full textChronic kidney disease (CKD) is associated with a very high cardiovascular (CV) risk, and CV disease is one of the main causes of death with a functioning transplant after kidney transplantation. Glomerular filtration rate (GFR) influences CV risk. The objective of this work was to compare for the first time CKD-patients and renal transplant recipients (RTR) with similar GFR level: 1) on the risk of overall mortality; 2) on aortic stiffness level (assessed by carotid-femoral pulse wave velocity, CF-PWV), a CV risk biomarker. The third objective was to compare pulse pressure (PP) and its evolution according to renal replacement therapy modality (dialysis or preemptive renal transplantation, PRT) in CKD patients pre-emptively registered on the kidney transplant waiting list.Methods. This work is based on the analysis of several cohorts. For the first objective, data came from CKD-REIN and DIVAT. CKD-REIN is a French prospective cohort performed in 40 nephrology consultations, including 3033 patients with moderate to severe CKD. The DIVAT register prospectively collects data of transplant recipients from 8 French centers, our study focused on the Nantes’ register. The second objective was studied in part of the prospective Parisian NephroTEST cohort of CKD-patients who were referred to the Physiology Unit of Tenon Hospital (Paris) for a one-day standardized evaluation, and of the RTR TransplanTEST cohort (retrospective cohort of 168 TR patients at Foch Hospital-Suresnes) evaluated in the same Physiology Unit. For these two objectives, RTR and CKD-patients were matched on a propensity score which included GFR among others. For the third objective, CKD-REIN patients who were pre-emptively registered on the kidney transplant waiting list were compared on PP level and on its evolution, according to the renal replacement therapy (RRT) modality initiated during the follow-up (dialysis or PRT). Results. In our first study, RTR was associated with an increased risk of overall mortality relative to the matched CKD-patients (HR: 2.6 [1.54-4.56], p=0.001 after adjusting for age, GFR and protide/creatinine urinary ratio). The increased risk appeared to be more related to an increased frequency of severe infections and neoplasms than to an increased CV risk. There was no difference between the two groups concerning the occurrence of at least one non-fatal CV event during the follow-up (HR: 0.8 [0.44-1.50], p=0.501). On the other hand, in the second study, RTR presented a significantly lower CF-PWV at 12-months after kidney transplant than the CKD-matched patients (10.1m/s vs 11.0m/s, p=0.008), unlike the evaluation performed at 3 months post-transplant (10.5m/s vs 11.0m/s, p=0.242). The improvement occurring within the 1st year of RT conferred to RTR assessed at 12 months a lower aortic stiffness level in comparison to the CKD-matched patients with similar GFR. After adjustment for age, mean arterial pressure, measured GFR, body mass index, diabetic status and serum PTH level, RT was associated with a 60% reduction in the risk of CF-VOP > 10.6m/s (median) at 12 months after RT (OR: 0.4 [0.23-0.68]). Finally, our latest (preliminary) results (third study) did not find any association between the RRT modality and PP evolution within the 6 months following RRT initiation in patients who were pre-emptively registered on the kidney transplant waiting list. The GFR decline in the year prior to RRT initiation was faster in-group of patients who initiate dialysis (with comparable CKD etiologies). Conclusion. Our results support the idea that, RT does not offset the excess mortality risk observed in CKD patients. At the same level of GFR, post-TR CV complications appear to be different from CV complications in CKD patients. Therefore, we believe that prevention and slowing CKD progression strategies must remain a priority in nephrology
Devine, Eric. "Increased removal of protein bound uremic toxins through reversible modification of the ionic strength during hemodiafiltration." Doctoral thesis, 2013. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-83583.
Full textEine große Zahl von Stoffwechselprodukten akkumuliert im Blut urämischer Patienten mit Nierenversagen. Da diese Moleküle schädliche Wirkungen auf die biologischen Funktionen haben, werden sie als Urämietoxine bezeichnet. Man teilt sie in drei Gruppen ein: 1) kleine wasserlösliche Substanzen (MG < 500 Da), 2) kleine, proteingebundene Substanzen (MG < 500 Da), 3) Mittelmoleküle (500 Da < MG < 60 kDa). Proteingebundene Urämietoxine werden wegen ihrer starken Proteinbindung und ihres Verteilungsvolumen durch klassische Hämodialyseverfahrens nur schlecht entfernt. Die prototypischen proteingebundenen Urämietoxine Indoxylsulfat (IS) und p-Cresylsulfat (pCS) sind bei chronischen niereninsuffizienten Patienten mit dem Fortschreiten der Niereninsuffizienz, Herz-Kreislauf-Erkrankungen und der Mortalität verbunden. Außerdem sind diese beiden Toxine an Albumin, dem wichtigsten Plasmaprotein, durch elektrostatische und/oder Van-der-Waals-Kräfte gebunden. Das Ziel der vorliegenden Arbeit war es, ein Dialyseverfahren basierend auf einer reversiblen Modifikation der Ionenstärke im Blut durch Erhöhung der Natriumchlorid (NaCl)-Konzentration zu entwickeln, um die Entfernung von proteingebundenen Molekülen wie IS und pCS zu erhöhen und dadurch eine Verbesserung des klinischen Verlauf der Patienten zu erreichen. Die Erhöhung der NaCl-Konzentration ([NaCl]) sowohl in normalem als auch in urämischem menschlichem Plasma war geeignet, um den proteingebundenen Anteil von IS und pCS durch Schwächung ihrer Bindungsaffinität zu Albumin zu verringern. Die Erhöhung der Ionenstärke während einer modifizierten Prädilutions-Hämodiafiltration (HDF) konnte durch eine Erhöhung der [NaCl] in der Substitutionslösung umgesetzt werden; dabei wurde der NaCl-Überschuss innerhalb des Dialysators vollständig entfernt. Dieses Verfahren war effektiv, um die Entfernungsrate beider proteingebundenen Urämietoxine zu steigern; seine Ex-vivo-Hämokompatibilität war allerdings aufgrund des osmotischen Schocks infolge der hohen [NaCl] im Substituat begrenzt. Deshalb wurde eine Iteration der modifizierten Prädilutions-HDF durch Einbau eines zweiten, seriellen Dialysators vorgenommen, bezeichnet als serielles Dialysator System (SDial). Diese letzte Methode wurde dann bezüglich der Durchführbarkeit, der Hämokompatibilität und Toxinentfernung validiert. Durch das SDial-System konnte, verglichen mit der modifizierten Prädilutions-HDF, eine bessere Hämokompatibilität bei ähnlicher Wirksamkeit erzielt werden. Beide Methoden, modifizierte Prädilutions-HDF und SDial System, wurden abschließend in ein Tierdialysemodell mit Schafen transferiert, wobei eine zufriedenstellende Biokompatibilität demonstriert werden konnte. Beide, zur vorübergehenden Erhöhung der Ionenstärke im Blut entwickelten Dialyseverfahren zeigten bei zufriedenstellender Biokompatibilität eine verbesserte Entfernung proteingebundener Urämietoxine durch Reduktion ihrer proteingebundenen Fraktion. In einem nächsten Schritt sind klinische Studien erforderlich, die diese Konzepte bezüglich ihrer In-vivo-Wirksamkeit und ihrer langfristigen Wirkung auf den Krankheitsverlauf untersuchen
Keepers, Tiffany Rae. "Renal inflammation in a shiga toxin plus lipopolysaccharide induced murine model of hemolytic uremic syndrome." 2007. http://proquest.umi.com/pqdweb?did=1801471441&sid=4&Fmt=2&clientId=3507&RQT=309&VName=PQD.
Full textHsieh, Chin-Wen, and 謝晉文. "The Effect of Uremic Toxin Indoxyl Sulfate on Osteogenesis in Bone Marrow Mesenchymal Stem Cells." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/7dx6h3.
Full text高雄醫學大學
醫學研究所碩士班
106
Background: Renal osteodystrophy is a serious health concern for patients with chronic kidney disease (CKD). Low turnover bone disease, which is one of the histological categories of renal osteodystrophy, are becoming more prevalent. Clinical studies have proven the negative correlation between the serum levels of uremic toxin indoxyl sulfate (IS) and bone-specific alkaline phosphatase in chronic hemodialysis patients, which indicates that IS relating to the decrease of bone formation. In vivo studies have also demonstrated that IS inhibits bone formation. However, few in vitro studies evaluated osteogenic differentiation using a non-cytotoxic concentrations of IS in bone marrow-derived mesenchymal stem cells (BMSCs). Accordingly, the molecular mechanisms of IS affecting osteogenesis in BMSCs requires further investigation. Methods: D1 cells are mouse BMSCs and were used for this study. MTT assay and lactate dehydrogenase assay were used to search the non-cytotoxic concentrations of IS. The effect of IS on osteogenic differentiation of D1 cells was evaluated by osteogenic gene expression using quantitative real-time polymerase chain reaction and mineralization using alizarin red S staining. Results: The results of IS affecting D1 cells viability showed that IS at concentrations of 100 to 400, 75 to 400, and 75 to 400 μM significantly decreased MTT activity (P < 0.05, P < 0.01, and P < 0.05, respectively) and at concentrations of 75 to 400 μM elevated lactate dehydrogenase leakage of D1 cells at 1, 2, and 3 days (P < 0.05) after starting the cell culture, respectively. The IS at concentrations of 25 to 400 μM was used to test osteogenic differentiation of D1 cells. The results showed that the quantity of D1 cells which was measured by DNA quantification assay was not affected by IS at concentrations ranging from 25 to 400 μM during osteogenic differentiation. IS at concentrations of 25 and 50 μM, which did not affect the viability of D1 cells during proliferation, reduced osteogenic differentiation without influencing cell quantity at 7 and 10 days (P < 0.01) after osteogenic induction. In mechanistic studies, IS at concentrations of 50 to 200 μM (P < 0.05) downregulated BMP-2 expression during the early stages of osteogenic differentiation, and IS at concentrations of 25 to 200 μM (P < 0.01) downregulated ALP and OC expression during the late stages of osteogenic differentiation. Conclusions: In this study, we found that IS of 25 to50 μM reduced osteogenic differentiation of BMSCs without influencing cell viability. The effective concentrations of IS found in this study are at the average serum concentrations of IS in patients with CKD. From this finding, we suggest that IS is a crucial factor contributing to low bone turnover in patients with CKD. Abbreviation: MTT: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide BMP-2: bone morphogenetic protein 2 ALP: alkaline phosphatase OC: osteocalcin
Psotka, Mitchell Adam. "The pathophysiology of renal failure in a shiga toxin plus lipopolysaccharide induced murine model of hemolytic uremic syndrome." 2008. http://proquest.umi.com/pqdweb?did=1805440271&sid=3&Fmt=2&clientId=3507&RQT=309&VName=PQD.
Full textThompson, Morgan Paige. "Changes in tissue expression of coagulation-related molecules after challenge with coagulopathic Shiga toxin-2." Thesis, 2017. https://hdl.handle.net/2144/23879.
Full textJhuang, Kai-Fu, and 莊凱富. "Study the effect of a uremic toxin p-Cresyl sulfate on mouse bone marrow-derived dendritic cells." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/4t7dg9.
Full text國立臺灣大學
免疫學研究所
106
p-Cresol sulfate is a toxin produced by bacteria in the intestine. It is usually filtered by the renal glomerulus in the kidney. However, if the function of the kidney is impaired, these toxins will continuously accumulate to form uremia and the immune system will become abnormal. There are some reports on the cause of the decline in immunity caused by p-Cresol sulfate, but there have been no studies on dendritic cells. Since dendritic cells play an important role in initiating the immune response, we investigated whether p-Cresol sulfate affects the function of dendritic cells. Preliminary studies have found that p-Cresol sulfate does not cause dendritic cell death at high concentrations, but inhibits the activation process induced by lipopolysaccharide, including the inhibition of CD40 expression, and the production of some cell cytokines. In the condition of co-culture with T cells, the ability to proliferate is not affected, whereas IFN- has a tendency to decrease and reach significant differences.It is speculated that p-Cresol sulfate may impair the function of the dendritic cells and reduce the immunity. The research of p-Cresol sulfate in dendritic cells continues to be further explored.
Parello, Caitlin Suzanne Leibowitz. "Investigating the contributions of leukocyte responses and kidney cell stress on Shiga- toxin pathogenesis." Thesis, 2015. https://hdl.handle.net/2144/15616.
Full textPai, Yi-Hsin, and 白憶欣. "Effect of potential probiotics on reducing uremic toxin indoxyl sulfate using the cisplatin-induced acute kidney injury rat model." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/60117169221621554162.
Full text國立臺灣大學
動物科學技術學研究所
102
Numerous molecules that are either excreted or metabolized by the kidney accumulated in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) is a protein bound uremic toxin, which is unable to effectively eliminate by haemodialysis (HD). The accumulation of protein-bound uremic toxins has been suggested to be related to complications and mortality in HD patients. Indole, the precursor of IS, are produced by intestinal bacteria, such as Escherichia coli, from tryptophan. Since uremic toxins might be reduced by modulating microbiota in the colon, probiotics seem to be potential to reduce the concentration of intestinal nitrogenous metabolites. Thus, the aim of this study was to find potential probiotics which may improve renal function by reducing IS production. Three strains, Lactobacillus plantarum, L. paracasei and Streptococcus thermophilus, were selected to have the ability to reduce indoxyl sulphate in vitro. Combination of strains (Pm-1) demonstrated a better IS removing ability than individual strains. We further investigated the uremic toxin-reducing probiotics by the cisplatin-induced acute kidney injury (AKI) rat model. Results indicated that oral administration of Pm-1 in cisplatin-induced acute kidney injury model significantly suppressed the accumulation of IS in the serum. Oral administration of Pm-1 also decreased in the number of E. coli and coliforms in feces. We further optimized growth medium by response surface methodology (RSM) with sequential quadratic programming (SQP). Results indicated that the media with sugar yeast, maltodextrin and dipotassium as major component could yield the highest cell numbers to 9.01、8.71 and 8.94 log/mL, respectively. The cost of medium was reduced to less than 20% when compared with commercial MRS medium. Our findings suggest that long term treatment with the strain combination Pm-1 might be a useful approach to decreasing IS accumulation in the serum and kidney. The possible mechanisms involved might include the binding/metabolizing IS in intestine and/or the modulation of bacterial growth in colon by Pm-1, both of which could decrease IS accumulation. The stimulation of anti-inflammatory cytokines and release of oxidative stress by Pm-1 might also be involved in the amelioration of AKI symptoms.
Niu, Shuo. "Regulation Of Innate Immune Cell Response Under Sub-acute/Chronic Inflammatory Conditions." 2017. http://scholarworks.gsu.edu/biology_diss/191.
Full textWU, SHU-CING, and 吳書晴. "Toxic effects of uremic toxins and antioxidants on renal tubular epithelial cell." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/p8utf5.
Full text弘光科技大學
營養醫學研究所
107
The uremic toxins existed in human body which can be produced from food digestion and metabolism. The accumulation of toxins can worsen kidney function in chronic kidney patients. The most well-known toxins in the world are the protein-bound organic compounds such as indoxyl sulfate and p-cresyl sulfate. These toxins cannot be removed by hemodialysis. The uremic toxins induce oxidative substances increases leading to oxidative stress and inflammation. Therefore, uremic toxins can induce cellular senescence and cell death of renal tubular epithelial cells. Curcumin and γ-tocopherol have anti-oxidative and anti-inflammation function. Therefore, the aim of the present study was to observe the cell growth, morphological change, cell cycle, and apoptosis-related proteins levels on PCS- and IS-treated renal tubular epithelial cells (NRK-52E) and human proximal tubular epithelial cells (HK-2) with curcumin or γ-tocopherol treatment. Our data shows that PCS and IS could inhibit cell growth in NRK-52E cells and HK-2 cells. Compared to the control group, 8μΜ curcumin could decrease viability of NRK-52E cell. Combination treatments with 8μΜ curcumin and high concentration of PCS displayed the synergistic effects. However, 10μΜ γ-tocopherol did not influence viability on PCS-treated NRK-52E cell. Interestingly, 10 μΜ γ-tocopherol could promote cytotoxic effects on PCS-treated HK-2 cells while the 8 μΜ curcumin had no synergistic effects on PCS-treated HK-2 cell. Observation on cell cycle by using flow cytometry, our result showed that 8μΜ curcumin and 10μΜ γ-tocopherol could increase sub-G1 and S phase whereas could decrease G1 phase on PCS-treated cells. In addition, the proteins levels of cleaved PARP、cleaved caspase 3 were increased by 8μΜ curcumin and 10μΜ γ-tocopherol treated on PCS-treated cells.
Ting, Ke Ya, and 柯雅婷. "The effect of Uremic Toxins Indoxyl Sulfate and Asymmetrical Dimethylarginine on Renal Cells." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/92325055168413594674.
Full text國防醫學院
生物化學研究所
102
Chronic kidney disease is a common complication in diabetes who have problems not only in glucose metabolic but also in protein and fat metabolize resulting in the nutritional imbalance. Most metabolites must be reabsorbed and exclusion to the urine by the kidney . This phenomenon commonly is known as uremic poisoning (uremia). Indoxyl sulfate (IS) and asymmetric dimethylarginine (ADMA) are two mainly components of uremia. IS is primarily transported by organic anion transporters (OATs) to urine excreted via the kidney , and ADMA is transported by organ ic cation transporter 2 (OCT2). My thesis was aimed to determine whether IS and ADMA have the ability to modulate the specific transporter proteins or progress the renal failure. Experimental result showed that the specificrenal transporter proteins were downregulated when renal proximal tubule cells treated with IS and ADMA. In addition, we also observed that both IS and ADMA induced the phosphorylation of histone H3 serine residue 10. Our results suggest that IS and ADMA can reduce the expression of transporter proteins which may increase themselves accumulation and more progression renal failure. We will further examine whether IS and ADMA-induced the phosphorylation of histone H3 serine residue 10 which is responsible for previous study of glucose transporter 1 by IS. Our work will provide novel insights of uremic toxin in human physiopathologic roles.
SAHOO, SRAVANI, and 夏凡妮. "Fabrication of Heparin Mimic PEDOT:PSS and Zeolite for the Removal of Uremic Toxins." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/vsmu4f.
Full text明志科技大學
材料工程系碩士班
108
Removal of uremic toxins using polymeric based haemodialysis membrane is implied to be the most constructive approach presently. In pursuit of a proper haemodialysis membrane possessing the characteristic of biocompatibility and effective capability of purification of blood, herein we have developed a polymeric membrane comprising of composite Nano fibre mats embedded with zeolite and PEDOT: PSS, which removes the uremic toxins effectively in the treatment of renal failure. We have fabricated these fibres with zeolite and poly (3,4ethylenedioxythiophene): poly (styrenesulfonate) by the process of electrospinning on a filtering PES membrane. Through the process of electro spinning, the zeolite and PEDOT: PSS fibres were uniformly spread on the PES membrane and were annealed at 130 0C successively. Condensation reaction between the poly (styrenesulfonate) PSS and poly (ethyl oxide) PEO occurred during the process of annealing, which provided the fibres with greater wet stability in PBS buffer. These fibres were distributed uniformly in the matrix on PES membranes as revealed by the images of scanning electron microscopy. This zeolite and PEDOT: PSS fibres were then introduced in haemodialysis bio-electronic device equipped with a peristaltic pump. The temperature of the dialyzer was maintained at 37ᴼC. Here, the adsorption of uremic toxins occurs through diffusion. These zeolite and PEDOT: PSS fibres exhibits excellent performance in filtering out and removing the free uremic toxins. These filtered uremic samples were collected at one hour interval for four hours. The UV-vis absorption spectroscopy of the samples reveals the successful exclusion of uremic toxins. The experimental results indicate that the proposed zeolite and PEDOT: PSS hybrid nano fibres provide greater efficiency as a suitable haemodialysis membrane. KEYWORDS: ZEOLITES, PEDOT: PSS, PES, ELECTROSPINNING, COMPOSITE FIBRES, HEMODIALYSIS, BIOCOMPATIBILITY.
Garcia, Andreia Sofia Rodrigues. "Influence of uremic toxins on microbial intestinal epithelial barrier translocation in chronic kidney disease." Master's thesis, 2019. http://hdl.handle.net/10773/28406.
Full textDoença renal crónica (DRC) é um termo geral para distúrbios que afetam a estrutura e a função do rim. A perda progressiva da função renal conduz à acumulação de toxinas, toxinas urémicas, normalmente excretadas pelos rins. É nessas circunstâncias que o "estado urémico" é estabelecido. Estudos recentes relacionam o plasma urémico ao dano da função da barreira intestinal e à depleção dos constituintes proteicos das junções de oclusão (JO). No lúmen intestinal, a ureia é hidrolisada pela urease microbiana, formando grandes quantidades de amónia, o principal mediador da disrupção da barreira intestinal em condições urémicas, causando uma depleção das proteínas das JO epiteliais intestinais na DRC. Quando o ecossistema microbiano é afetado, espécies microbianas prejudiciais podem crescer excessivamente, assim como os seus produtos do metabolismo, conduzindo a um desequilíbrio do microbioma intestinal. Estudos recentes sugerem que o microbioma intestinal exerce influência na produção de toxinas urémicas e na progressão da DRC. Na DRC, o dano da função da barreira intestinal pode permitir a translocação de microrganismos intestinais, endotoxinas, antigénios e outros produtos microbianos do lúmen intestinal para a circulação sistémica, contribuindo para a patogénese de inflamação sistémica, risco cardiovascular e progressão da DRC. O nosso principal objetivo foi avaliar a aplicação de dois modelos in vitro de barreira epitelial intestinal para o estudo da translocação microbiana e avaliar o impacto de diferentes condições urémicas presentes na DRC nessa translocação microbiana. Para isso, analisamos o efeito do plasma de doentes com DRC e da toxina urémica ureia na translocação intestinal microbiana, assim como na integridade, permeabilidade e localização e quantidade das proteínas das JO nos modelos intestinais in vitro, monocultura Caco-2 e modelo triplo Caco-2/HT29-MTX/Raji B. Os resultados mostraram que as condições urémicas experimentais simuladas neste estudo não potenciaram a translocação microbiana, embora tenham interferido em certa medida com a integridade e a permeabilidade dos modelos de barreira epitelial intestinal. A translocação microbiana foi maior na monocultura Caco-2 do que no modelo triplo, sugerindo que o modelo triplo cria uma barreira mais eficaz e, portanto, aparentemente representa um modelo intestinal mais robusto do intestino humano. Este estudo permitiu concluir que o estado urémico influencia a integridade da barreira intestinal, mas que essa influência pode não estar diretamente relacionada com um aumento da translocação microbiana através do epitélio intestinal nos modelos in vitro estudados.
Mestrado em Biomedicina Molecular
CHUNG, CHUAN-KAI, and 鍾傳鎧. "Development of Conductive Polymer Composite materials Sponge for Removal of Protein-bound Uremic Toxins." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/m5k48c.
Full text明志科技大學
材料工程系碩士班
107
For hemodialysis treatment, protein-bound uremic toxins (PBUTs) are difficult to eliminate by dialysis. Therefore, these toxin accumulations will become participants in numerous pathological changes observed in patients with kidney disease. In this work, we have developed an efficient and safe and biocompatible hemoperfusion (HP) device for the removal of protein-bound uremic toxins from artificial biological fluids. Adsorbent Blood Perfusion Device Through Quantitative GOPS (3-Glycidyloxypropyl) (trimethoxysilane) and Different Doping Agents [Multiwalled Carbon Nanotubes (MWCNTs); Zeolite; Graphene Oxide (GO)]-Poly (3,4) - Ethylenedioxythiophene : poly (styrene sulfonic acid) (PEDOT: PSS) nanocomposite technology applied freeze drying process to produce conductive polymer nano composite sponge. In this study, we first evaluated the static behavior of urea toxins with different adsorbents [zeolite; carbon nanotubes; graphene oxide] against urine toxin (P-cresol, Indoxyl sulfate, hippuric acid, creatinine) and observed adsorption. effectiveness. For material analysis, we performed morphological analysis of the material by scanning electron microscopy and electroanalyzed the material using a four-point probe and potentiostat. Finally, we performed a perfusion experiment for more than four hours to evaluate the dynamic adsorption efficiency of four urea toxins with polymer conductive polymer nanocomposite sponges.
Wang, Sheng Chuan, and 王生銓. "Clearance of Uremic Toxins from Simulated Serum Using Electrospun and Electrosprayed Cellulose Triacetate Fibrous Membrane." Thesis, 2019. http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107CGU05063030%22.&searchmode=basic.
Full textMotomochi, Amanda. "Cell stress markers during development of hemolytic uremic syndrome and acute kidney injury." Thesis, 2014. https://hdl.handle.net/2144/14397.
Full textMayer, Chad. "Shiga toxins and damage-associated molecular patterns leading to endothelial dysfunction." Thesis, 2016. https://hdl.handle.net/2144/15270.
Full textYEN, SHIH-CHIEH, and 顏士傑. "Studies on Electrospun Carbon Nanotube-Conducting Polymer Composite Nanofiber Membranes for Efficient Removal of Protein-bound Uremic Toxins." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/9bvn57.
Full text明志科技大學
材料工程系碩士班
106
Herein we have developed an integrated electrospinning approach for producing a wide-range of high quality three-dimensional (3D) carbon nanotube/conducting polymer composite nanofiber mats as the bioelectronic interfaces (BEIs), which can be further assembled on ultrafiltration membranes for efficient removal of uremic toxin. We use the multiwalled carbon nanotubes (MWCNT)-poly(ethylene oxide) (PEO)- poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) quaternary blends made of nanofiber membranes. By a condensation reaction between poly (styrenesulfonate) PSS and poly (ethylene oxide) (PEO) under a high temperature treatment (130 oC for 6 hours) to form a chemical crosslinking reaction, Nanofiber mats to improve long term wet stability in PBS buffer. Finally, we integrated the nanofiber-based samples on the dialysis membrane and further assembled into a hemodialysis (HD) bioelectronic device with the use of peristaltic pump for evaluating the influence of various MWCNT additives on the removal efficiency of uremic toxins.
Peng, Yu-Sen, and 彭渝森. "Effects of Protein-bound Uremic Toxins on the Adherens Junctions of Vascular Endothelial Cells and Cardiomyocytes and the Underlying Mechanisms." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/99477639803172952417.
Full text國立臺灣大學
解剖學暨細胞生物學研究所
101
Chronic kidney disease patients have a much higher risk of cardiovascular diseases and death than general population. Uremic toxins are probably involved in the development of vascular endothelial dysfunction and cardiac arrhythmia. Indoxyl sulfate (IS) and p-cresol are both uremic toxins that accumulate with deterioration of renal function. This study explored the effects and underlying mechanisms of IS and p-cresol on the adherens junctions (AJs) of vascular endothelial cells and cardiomyocytes, respectively. In the first section of study, bovine pulmonary artery endothelial cells (BPAECs) model was adopted. After treatment with IS, the immunofluorescence study showed significantly decreased staining of vascular endothelial cadherin (VE-cadherin), p120-catenin, and β-catenin. IS treatment resulted in disruption of intercellular contacts between BPAECs with prominent parallel-oriented intracellular stress fiber formation. Intracellular free radical levels which measured by flow cytometry increased after IS treatment. Pre-treatment with antioxidant, MnTMPyP, and an ERK pathway inhibitor, U0126, both significantly prevented IS-induced disruption of intercellular contacts. Western blotting analyses demonstrated that IS induced phosphorylation of myosin light chain kinase (MLCK) and myosin light chains (MLC) as well as activation of extracellular-signal-regulated protein kinase (ERK1/ERK2). Pretreatment with MnTMPyP prevented ERK2 phosphorylation. U0126 prevented the IS-induced MLCK and MLC phosphorylation. MEK-ERK acted as the upstream regulator of the MLCK-MLC pathway. These findings suggest that the superoxide anion-MEK-ERK-MLCK-MLC signaling mediates IS-induced cell contraction and junctional dispersal of BPAECs. The second section of study was carried in the model of neonatal rat cardiomyocytes. The p-cresol treatment decreased cardiomyocyte contraction rates and resulted in arrhythmic contraction. In immunofluorescence experiment, a loss of N-cadherin and p120-catenin immunostaining from cell-cell contact sites was noted after p-cresol treatment. P-cresol disrupted AJs and caused the formation of intercellular gap formation. Flow cytometry and Western blotting analyses revealed that p-cresol treatment increased intracellular calcium levels and protein kinase Cα (PKCα) phosphorylation. The immunoprecipitation experiment revealed that PKCα activation induced serine dephosphorylation of p120-catenin, dissociation of p120-catenin and N-cadherin, and AJs disassembly. Inhibition of PKCα by Go 6976 blocked the above effects. Thus, p-cresol caused AJs disassembly between cardiomyocytes, which was mediated by intracellular calcium influx-PKCα activation-p120catenin serine dephosphorylation. This cascade was further confirmed in the study of H9c2 cells by siRNA approach. siRNA knockdown of PKCα prevented p-cresol-induced intercellular gaps formation, AJs disassembly, and serine dephosphorylation of p120-catenin. Our study showed that uremic toxin indoxyl sulfate and p-cresol caused vascular endothelial cell and cardiomyocyte AJ disassembly, respectively. These findings agree with the previously reported findings that indoxyl sulfate and p-cresol are associated with cardiovascular disease in chronic kidney disease populations.Additional studies are needed to elucidate the detailed molecular pathways and possible treatment policy.
Lin, Cheng-Jui, and 林承叡. "The effects of GI-related protein-bound uremic toxins on endothelial progenitor cell function and clinical outcomes in chronic kidney disease." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/7z7437.
Full text國立臺北科技大學
工程科技研究所
102
Cardiovascular diseases (CVD) are still the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Development of accelerated atherosclerosis involves multiple risk factors. However, traditional risk factors could not fully account for the high risk of CVD in CKD patients. Recent studies supported the idea of non-traditional risk factors, which included renal anemia, oxidative stress and uremic toxins. Protein-bound uremic toxins including indoxyl sulfate (IS) and p-cresyl sulfate (PCS) accumulated while renal function decline have been reported having adverse effect on endothelial cells (ECs) function by increasing production of oxidative stress and free radical. Endothelial dysfunction has been regarded to be the essential step resulting in CVD. However, recent studies also showed endothelial progenitor cells (EPCs) could function to restore the endothelial function damaged during coronary ischemia. It is still unclear whether IS or PCS will lead to EPCs dysfunction. Thus, our purpose is to further investigate the pathological effects of IS and PCS from in vitro to in vivo study. Our results showed that IS had obvious negative effect on angiogenesis of human umbilical vein endothelial cells (HUVECs) and EPCs. The ability of EPCs migration, colony forming unit and proliferation were also inhibited by IS and PCS in a dose dependent manner. In addition, we also found the human endothelial function evaluated by flow mediate dilation (FMD) was significantly decreased in advanced CKD. The FMD value was negatively correlated to serum IS and PCS levels after adjusting other confounding factors. Moreover, we also explore the effects of IS and PCS on multiple clinical outcomes in CKD. Form our research, it showed IS and PCS were capable of predicting CVD event and kidney function deterioration in patients with CKD stage 3-5. For hemodialysis patients, PCS was strongly associated with CVD event, hospitalization event and vascular access failure. Both toxins were also a valuable surrogate to evaluate the event of CVD, mortality and peritoneal dialysis (PD) failure in PD cohort. From our results above-mentioned, it indicated that higher serum IS and PCS levels were closely related to worse clinical outcomes. We speculate that these adverse outcomes may contribute directly or indirectly to the loss of endothelial cell function owing to inhibition of EPCs function by IS or PCS.
You, Hong Lin, and 游鴻霖. "Preparation of Porous Polymer Inclusion Membranes by Non-solvent Induced Phase Inversion for Selective Clearance of Uremic Toxins from Simulated Serum." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/vjer56.
Full textKe, Jia Wen, and 柯佳妏. "Preparation of Porous Mixed-Matrix Membrane by Non-solvent Introduced Phase Inversion for the Clearance of Small Uremic Toxins from Simulated Serum." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/9x5ekj.
Full textPage, Andrea Vaughn. "Angiopoietin-1 and -2 in Infectious Diseases associated with Endothelial Cell Dysfunction." Thesis, 2012. http://hdl.handle.net/1807/32274.
Full textLee, Yun-Wei, and 李芸維. "I. Development of capillary electrophoresis for determination of protein-bound uremic toxins in the serum of hemodialysis patientsII. Synthesis of fluorescence polymer dots for analysis of deferiprone in human plasma." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/12293914764285367838.
Full text高雄醫學大學
藥學系碩士班
105
One capillary electrophoresis (CE) method had been developed for simultaneous determination of protein-bound uremic toxins in the serum of hemodialysis patients. The other method, chemical sensor, had also been developed for determination of iron chelating medicine in the plasma of β-thalassemia patients. The first part of the thesis is determination of four uremic toxins in the serum of chronic kidney disease (CKD) patients, including indole-3-acetic acid (IAA), para-cresol sulfate (pCS), 3-indoxyl sulfate (3-INS), and hippuric acid (HA), by field-amplified sample stacking-sweeping-micellar electrokinetic chromatography (FASS-sweeping-MEKC). Chemometric experimental design was used to determine the optimal condition for analysis. The p value of the concentration of phosphate buffer and SDS and pH value of phosphate buffer were less than 0.05, indicating that the factors affected the separation in statistical significance. In a further discussion, the optimal condition was set at 100.00 mM NaH2PO¬4 (pH 4.0) containing 150.00 mM SDS and 7.50% MeOH. The separation could be finished within 15 minutes. The calibration curves were established by standard addition method. The limit of detection (LOD) of IAA, pCS, 3-INS and HA were 0.08, 0.28, 0.34, and 0.25 μg/mL, respectively. The relative standard deviation (RSD) was less than 14.15% and the relative error (RE) was less than 13.71%. The proposed method could be successfully applied in quantitative determination of the four uremic toxins in the serum of 100 hemodialysis patients. The second part of the thesis is determination of iron chelating medicine in the plasma of β-thalassemia patients by fluorescent polymer dots (Pdots). The PFBT (poly(fluorene-alt-benzothiadiazole)) polymer dots functionalized with PSMA (poly(styrene-co-maleic anhydride)) polymer was synthesized by reprecipitation. The optimal condition for pretreatment of plasma samples was deproteinized with acetonitrile and salting-out with ammonium sulfate. The optimal condition for analysis is using 50.00 μg/mL copper ions to quench the fluorescence of the Pdots which diluted with 10.00 mM HEPES buffer (pH 6.0) and the fluorescence was recovered by adding the pretreated plasma samples containing deferiprone (DFP). The pretreatment time of plasma samples was only 10 minutes and the reaction time was less than 1 minutes, indicating that the proposed method could be applied in the rapidly screening plasma samples from β-thalassemia patients. The LOD was 2.50 μg/mL and the linear range was 5.00-30.00 μg/mL. The RSD and RE were lower than 12.23% and 14.82%, respectively. The specificity of the method was good. The proposed method could be successfully applied in quantitative determination of the DFP in the plasma of 2 β-thalassemia patients. The specificity test was ongoing.