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1
Guerra, Francisco. "Bloody Good: Pros of Synthetic Blood Substitutes." Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/243889.
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In today's society we unfortunately have and will continue to face the effects of issues such as war, poverty, trauma, and death; all of which have had an impact on the lives of people within these societies, be it religious, medical or social. An important, yet subtle common denominator present within these issues is blood. Blood and its transfusion have had an enormous impact on these issues and disappointingly, today doctors have been facing increasing difficulties with providing blood to those who need it; mainly shortages and donor complications. Today and in past decades researchers and medical doctors have been increasing their focus on the study of blood and its many fascinating features so as to create a relatively ideal blood substitute. The focus of this thesis is to acknowledge the progressions being made in the creation of blood substitutes and to gain an understanding of the positive impacts it would have on society as a whole. With blood substitutes one would not have to worry about donors, infections, or shortages. We delve into a world full of issues related to blood where scientists strive to create a substance that can meet the important goal blood accomplishes; maintaining life.
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Guerra, Andres. "Bad Blood: Cons of Synthetic Blood Substitutes." Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/243959.
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In recent years scientists have been attempting to develop synthetic blood substitutes in order to counter both the shortage in donor blood and the problems associated with infection and disease during allogeneic transfusion. Most attempts have been made at mimicking the oxygen carrying capabilities of red blood cells yet there is still a broad array of substances in use today that try to simulate the effects of whole blood, not just the red blood cell itself. This literature based thesis extensively discuses the importance of all blood components and reviews the recent developments and problems associated with volume expanders, oxygen carriers which are further subcategorized into hemoglobin-based substitutes and perfluorocarbons, erythropoietin use, and autologous blood transfusions. Their short term use has potential benefits but in the long term some of their shortcomings include hypertension, hypoproteinemia, thrombus formation, abnormal vasoactivity, anaphylaxis, and ischemic reperfusion injury, all of which tend to overshadow their benefits.
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Bentley, P. K. "Biocompatibility assessment of novel perfluorochemical emulsions." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293632.
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Armstrong, F. H. "Tissue responses to perfluorochemical emulsion components in rats." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276220.
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Ferreira, Margarida Lourenço. "New Artificial Blood Substitutes using Fluorinated Ionic Liquids." Master's thesis, Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica António Xavier, 2016. http://hdl.handle.net/10362/69823.
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"In the past decades, safe and effective artificial oxygen carriers (AOC), also named as “blood
substitutes”, have been proposed and extensively studied in chemistry and medical science. The constant
necessity of donor blood is crucial for diverse medical situations, such as accidents and casualties which
result in acute blood loss and the need to restore oxygen transport to the tissues. The inherent
complications associated to the traditional blood transfusion make urgent the formulation of new
suitable alternatives.(1–4)(...)"info:eu-repo/semantics/publishedVersion
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Alayash, Abdu I. "Hemoglobin-based blood substitutes : redox, signalling and clearance mechanisms." Thesis, University of Essex, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528868.
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Ning, Jing 1953. "Studies of perfluorochemical surfactant XMO-10 : effect on perfluorochemical blood substitutes." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=64471.
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Mobed, Maryam. "Purification and characterization of carboxymethylchitin-coated liposomes encapsulating hemoglobin as potential blood substitutes." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=60008.
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To increase the survival time of the liposome-based artificial red blood cells in vivo, bovine hemoglobin-loaded liposomes (LEHb) are coated with a polyanionic polymer. The purpose is to simulate the presence of a protective negative charge on the surface of living cells arising from the carboxylic extremities of sialoglycoproteins. In order to predict the in vivo response, the necessary experiments for the in vitro system characterization have been carried out.The purified LEHbs display a unimodal size distribution in the submicron range. Analysis of the lipid/Hb content of the liposomes reveals that the variations in the Hb encapsulation efficiency (E$ sb{ rm Hb}$) as a function of the initial Hb concentration (Hb) $ sb{ rm o}$ are insignificant compared to the net augmentation of E$ sb{ rm Hb}$ as a function of the increasing initial lipid concentration. Meanwhile high (Hb) $ sb{ rm o}$s are necessary for the preservation of oxyhemoglobin. A comparative study suggests that FT-IR spectroscopy gives a more accurate quantitative adsorption index while the chitinase-based enzymatic assay should be used as a qualitative detection tool.
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Rainbow, Willa Augusta. "Regulation of circulation in the presence of blood substitutes: hormonal and renal influences." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 1986. http://digitalcommons.auctr.edu/dissertations/2803.
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Oxy-Pherol-ET (OP-ET) is an artificial blood substitute composed of perfluoro~ributylamine (FC-43) emulsified with pluronic (FC-68) and hydroxyethyl starch as a plasma expander. This blood substitute is quite unique in that it has a high oxygen and carbon dioxide carrying capacity and is inert. In order for OP-ET to work, it must co-exist in circulation with blood components. This research project has been an investigation of the effect of OP-ET on the circulation regulatory agents (hormonal, etc). The aorta and vena cava were examined to assess the influence of OPET on the structural components of circulation. Since the kidney plays an important role in the overall regulation of circulation, the influence of the OP-ET on its function and structure were examined also.
Stimulation of the renin-angiotensin system by hemorrhage, low sodium diet (LSD), and reduced renal perfusion pressure resulted in an increased release of renin in animals treated with OP-ET. Animals previously exchange-transfused with OP-ET were subsequently monitored daily for changes in weight, water intake, and urinary salt and water output. In OP-ET treated animals weight increase was when slow compared to control animals. The water intake of the animals exchange-transfused animals was substantially greater than control animals for the same time period.
Animals prepared with indwelling catheters and exchange-transfused with OP-ET were monitored for their ability to respond to pharmacological concentrations of
catecholamines and angiotensin II. Under these conditions animals showed no significant difference in blood pressure response when compared to control animals that were exchange-transfused with donor animals' RBCs and treated similarly with angiotensin and catecholamines. Previously transfused animals were monitored to determine the effect of OP-ET on the kidney. Under these conditions there was a diuretic-induced immediate increase in urinary sodium excretion and a gradual increase in urinary potassium. These were expected responses for this diuretic agent.
Scanning electron microscopy (SEM) of exchange-transfused animals did not reveal observable differences within the endothelium of the aorta. The vena caval endothelium of the exchange-transfused animals showed no significant changes. There were no observable alterations in the glomerular capillaries by 7 days post-transfusion.
The data warrant the conclusion that mechanisms which normally regulate the circulation still function in the presence of the blood substitutes used in this study. The use of OP-ET has great potential in emergency medicine and remote areas of the world where whole blood would be difficult to maintain.
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Hernandez, Adrian V., Erin E. Emonds, Brett A. Chen, Alfredo J. Zavala-Loayza, Priyaleela Thota, Vinay Pasupuleti, Yuani M. Roman, Antonio Bernabe-Ortiz, and J. Jaime Miranda. "Effect of low-sodium salt substitutes on blood pressure, detected hypertension, stroke and mortality." BMJ Publishing Group, 2019. http://hdl.handle.net/10757/652462.
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Objective A systematic review and meta-analysis was conducted to assess the efficacy of low-sodium salt substitutes (LSSS) as a potential intervention to reduce cardiovascular (CV) diseases. Methods Five engines and ClinicalTrials.gov were searched from inception to May 2018. Randomised controlled trials (RCTs) enrolling adult hypertensive or general populations that compared detected hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), overall mortality, stroke and other CV risk factors in those receiving LSSS versus regular salt were included. Effects were expressed as risk ratios or mean differences (MD) and their 95% CIs. Quality of evidence assessment followed GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Results 21 RCTs (15 in hypertensive (n=2016), 2 in normotensive (n=163) and 4 in mixed populations (n=5224)) were evaluated. LSSS formulations were heterogeneous. Effects were similar across hypertensive, normotensive and mixed populations. LSSS decreased SBP (MD-7.81 mm Hg, 95% CI-9.47 to-6.15, p<0.00001) and DBP (MD-3.96 mm Hg, 95% CI-5.17 to-2.74, p<0.00001) compared with control. Significant increases in urinary potassium (MD 11.46 mmol/day, 95% CI 8.36 to 14.55, p<0.00001) and calcium excretion (MD 2.39 mmol/day, 95% CI 0.52 to 4.26, p=0.01) and decreases in urinary sodium excretion (MD-35.82 mmol/day, 95% CI-57.35 to-14.29, p=0.001) were observed. Differences in detected hypertension, overall mortality, total cholesterol, triglycerides, glucose or BMI were not significant. Quality of evidence was low to very low for most of outcomes. Conclusions LSSS significantly decreased SBP and DBP. There was no effect for detected hypertension, overall mortality and intermediate outcomes. Large, long-term RCTs are necessary to clarify salt substitute effects on clinical outcomes.Wellcome Trust
Revisión por pares
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Martinho, Susana Teresa Antunes. "Development of new oxygen therapeutics using fluorinated ionic liquids." Master's thesis, Faculdade de Ciências e Tecnologia, 2012. http://hdl.handle.net/10362/8482.
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Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau Mestre em
Engenharia BiomédicaThe last decade of the 20th century has yielded a remarkable progress in the field of first generation artificial blood substitutes. Emulsions based on perfluorocarbons (PFCs) became one of the main candidates for a safe and reliable artificial blood substitute. The final objective of the present work is to study the fluorinated ionic liquids (FILs) with the purpose of replacing, partially or totally, the PFCs actually used as artificial blood substitutes, thus providing new fluids with tailored advanced properties. With this goal in mind, the thermophysical and thermodynamic characterization of several FILs, was carried out with the aim to select the most appropriate candidate. This characterization involves the measurement and analysis of the decomposition and melting temperature, density, viscosity, refractive index, and ionic conductivity at atmospheric pressure in a temperature range from 298.15 to 353.15 K. Furthermore, the liquid-liquid equilibria of binary mixtures of PFCs and FILs were studied, at atmospheric pressure in a temperature range usually from 293.15 to 343.15 K. The knowledge of the phase behaviour is crucial to the formulation of emulsions used nowadays as suitable oxygen carriers. Finally, Non-Random Two Liquid (NRTL) thermodynamic model was successfully applied to correlate the behaviour of the binary mixtures of PFCs and FILs
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Zanusso, Ilenia. "Acellular matrices as tool for renal progenitor differentiation studies and tissue engineering of blood vessels." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3423024.
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AMs seem to be a very promising scaffold in TE and can be considered as temporary inductive site-appropriate templates to support the growth, differentiation, and function of the parenchymal cell population of each organ. Nowadays, TE techniques are used both to develop tissue substitutes ex vivo and as reliable tool to investigate cell behaviour, differentiation and proliferation in 3-dimentional environments.
In this work the following two different projects have investigated both potentialities using tissue-specific AMs:
1- influence of AMs on differentiation of kidney progenitor cells from amniotic fluid into mature renal cells;
2- AMs as biomaterial to develop vessel substitutes.
1- Kidney AMs (KAMs) were used to evaluate the differentiation of kidney progenitor cells from amniotic fluid into mature renal cells in order to better understand whether they could be suitable for future application in therapy. Renal progenitors were seeded into KAMs, which led them to proliferate, maintain podocyte phenotype and differentiate into tubular cells in vitro. To further evaluate the differentiative potential of KAMs, grafts composed of KAM with or without cells were intrarenal implanted into nude mice. In vivo, progenitors from amniotic fluid expressed mature renal markers, attracted inside KAMs murine cells presenting the same proteins and integrated into host structures.
2- Although autologous vascular grafts and artificial materials have been used for reconstruction of small diameter (5 mm) blood vessels, the poor availability of vessels and the occurrence of intimal hyperplasia and progressive atherosclerotic degeneration represent shortcoming of these vascular prostheses. Therefore, this study aimed to develop AM-based vascular grafts. Both AAMs alone and AAMs previously reendothelized with skin microvascular endothelial cells (ECs) were in vivo implanted and analyzed. The lack of reendothelization, leading to intimal hyperplasia and increased incidence of thrombosis observed in AAMs grafts, have indicated the need to provide in vitro an endothelial coverage of decellularized tissue. Indeed, grafts composed of AAM and skin microvasculature ECs shown good patency and no thrombi. Although these grafts appeared narrowed and a moderate hyperplasia has been detected in the inner layer, they presented two main advantages: they were obtained into a clinically relevant time frame and eliminated the need to remove healthy vessels for collecting autologous ECs.Le matrici acellulari rappresentano uno scaffold promettente per l’ingegneria tessutale. Infatti, la matrice extracellulare costituisce un supporto sito-specifico che favorisce la crescita e il differenziamento delle cellule di qualsiasi organo. Ad oggi, le tecniche dell’ingegneria tessutale sono utilizzate sia per lo sviluppo ex vivo di sostituti tessutali, che per studiare la proliferazione e la differenziazione delle cellule quando si trovano all’interno di uno scaffold tridimensionale. In questo lavoro di tesi, i due seguenti progetti sono andati a valutare entrambe le potenzialità di matrici acellulari tessuto-specifiche: 1- valutazione della capacità della matrice acellulare di indurre il differenziamento di progenitori renali da fluido amniotico in cellule renali mature; 2- valutazione della matrice acellulare per la sostituzione di vasi sanguigni. 1- La matrice acellulare renale è stata utilizzata per valutare la capacità differenziativa di progenitori renali da fluido amniotico in modo da valutarne una futura applicazione terapeutica. I progenitori renali sono stati seminati sulla matrice acellulare renale, che, in vitro, ne ha promosso la proliferazione, il mantenimento del fenotipo podocitario e la differenziazione in cellule tubulari. Per valutare in vivo il potenziale differenziativo di queste cellule, la matrice da sola o ripopolata con le cellule è stata impiantata all’interno di un rene di topo nudo. I progenitori renali si sono ulteriormente differenziati, si sono integrati all’interno delle strutture tubulari dell’ospite e hanno promosso la migrazione di cellule differenziate murine all’interno dello scaffold. 2- La matrice acellulare di aorta è stata utilizzata per lo sviluppo di sostituti vasali. Nonostante vasi autologhi o costituiti di polimeri sintetici vengano già utilizzati nella pratica clinica per la ricostruzione di vasi di piccolo diametro (5 mm), numerosi sono gli svantaggi legati al loro utilizzo, quali l’iperplasia della tonaca intima e la degenerazione arteriosclerotica. Lo scopo di questo studio è stato quello di sviluppare sostituti vasali utilizzando come scaffold vasi decellularizzati. Matrici acellulari da sole o ripopolate con cellule endoteliali da microcircolo sono state impiantate nell’aorta di ratto Lewis. Come osservato negli impianti di sola matrice acellulare, la mancanza della copertura endoteliale portava all’iperplasia dell’intima e all’aumento di incidenza dei processi trombotici, sottolineando la necessità di reendotelizzare in vitro il vaso decellularizzato prima dell’impianto in vivo. Infatti, i sostituti vasali costituiti da matrice acellulare e cellule endoteliali da microcircolo hanno dimostrato di avere una buona resistenza al flusso e non presentavano trombi al loro interno. Sebbene questi vasi fossero assottigliati e mostrassero una leggera iperplasia della tonaca intima, questo approccio presentava due principali vantaggi: permetteva di ottenere sostituti vasali in un tempo clinicamente utile ed eliminava la necessità di rimuovere vasi sani per ottenere cellule endoteliali autologhe.
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Styslinger, Thomas James. "The Development and Application of Novel Methods for the Chemical Glycosylation of Therapeutic Proteins & A Chemical Approach to Understanding Glycosyltransferases and Their Application in the Synthesis of Complex Carbohydrates." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313009079.
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Marques, Elsa Isabel Correia Cabo. "Moléculas simples com aplicação na medicina." Master's thesis, Universidade de Évora, 2009. http://hdl.handle.net/10174/19741.
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O trabalho apresentado, foi realizado no âmbito do mestrado em Química para o ensino, da Universidade de Évora e tem como tema " Moléculas Simples de Aplicação na Medicina". A abordagem deste tema deve-se à necessidade cada vez maior de um ensino que motive os alunos e lhes proporcione um gosto maior pelo estudo das ciências, uma vez que cada vez mais os jovens estudantes revelam pouca motivação e gosto pelo estudo das áreas científicas quer ao nível do ensino secundário quer ao nível do ensino superior. Pretende-se também tentar compreender e explicar o porquê das suas desmotivações e tentar adaptar novas abordagens a temas que suscitem nos jovens um maior interesse, uma melhor compreensão da importância das ciências, da tecnologia na vida quotidiana de todos nós no que respeita ao nosso bem-estar e à nossa saúde. Numa primeira parte é feita uma revisão sobre os principais conteúdos propostos a desenvolver em sala de aula, conteúdos esses que sustentam o estudo do xénon como anestésico e dos perfluorocarbonetos como substitutos do sangue. A segunda parte integra um programa orientador, seguindo as metodologias e estrutura do programa homologado pelo ME para o 12º ano de escolaridade, e protocolos de algumas actividades de carácter experimental laboratorial propostas. Estas actividades têm como finalidade estimular a curiosidade e facilitar a consolidação das matérias. ABSTRACT: The present study was carried out under the Master's Degree in Chemistry for Teaching, taught at the University of Évora under the theme "lmplementation of Simple Molecules in Medicine". The approach to this issue is due to an increasing need for teaching that motivates students and sharpen their senses for the study of science because, increasingly, young students show little motivation and passion for the study of science, both at secondary school and higher education terms. The aim is also trying to understand and explain the reason of their discouragement and try new approaches to issues that raise young in a better understanding of the importance of science and technology in everyday life for all of us in what concerns to our welfare and our health. ln the first part there is an overview of the major content areas to develop in the classroom. These contents support the study of xenon as an anesthetic and perfluorocarbons as blood substitutes. The second part includes the syllabus, following the methodologies and structure of the curriculum approved by the ME to the 12th grade and protocols of some activities for an experimental laboratory. These activities intend to stimulate curiosity and facilitate the consolidation of materials.
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Sathananthan, Saranya. "Modulating fibrin matrix properties via fibrin knob peptide functionalized microgels." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44905.
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Fibrin is the body's natural provisional matrix activated in response to vascular injury in which noncovalent knob:hole interactions between fibrin monomers lead to the assembly of fibrin for clot formation. In this study we aimed to exploit fibrin knob:hole affinity interactions with swelling, space filling microgels for the development of a potential bio-synthetic hybrid polymer system with hemostatic properties. Previous work has explored the inherent binding interactions of various fibrin knobs and their complementary polymerization holes, which have led to the development of fibrin knob peptide mimic (GPRPFPAC) with enhanced binding affinity for fibrin(ogen) holes. By coupling this enhanced fibrinogen binding peptide with a pNIPAm microgel system capable of being dynamically tuned and self-assembled, we hypothesized the specific and rapidly triggered formation of a bulk hydrogel in a wound environment (i.e. in the presence of fibrinogen). We found that at the peptide ligand density and concentrations of microgels used, that a rapid formation of a gel did not occur in the presence of fibrinogen alone. However with fibrinogen and thrombin, we found that fibrin network polymerization, structure, and viscoelastic properties were greatly altered in the presence of knob peptide-conjugated microgels.
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Shiu, Hoi Ting. "Controlling whole blood activation and resultant clot properties on various material surfaces : a possible therapeutic approach for enhancing bone healing." Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/63628/1/Shiu_Ting_Thesis.pdf.
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Injured bone initiates the healing process by forming a blood clot at the damaged site. However, in severe damage, synthetic bone implants are used to provide structural integrity and restore the healing process. The implant unavoidably comes into direct contact with whole blood, leading to a blood clot formation on its surface. Despite this, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing.
Surface chemistry of a biomaterial is a crucial property in mediating blood-biomaterials interactions, and hence the formation of the resultant blood clot. Surfaces presenting mixtures of functional groups carboxyl (–COOH) and methyl (–CH3) have been shown to enhance platelet response and coagulation activation, leading to the formation of fibrin fibres. In addition, it has been shown that varying the compositions of these functional groups and the length of alkyl groups further modulate the immune complement response.
In this study, we hypothesised that a biomaterial surface with mixture of –COOH/–CH3(methyl), –CH2CH3 (ethyl) or –(CH2)3CH3 (butyl) groups at different ratios would modulate blood coagulation and complement activation, and eventually tailor the structural and functional properties of the blood clot formed on the surface, which subsequently impacts new bone formation.
Firstly, we synthesised a series of materials composed of acrylic acid (AA), and methyl (MMA), ethyl (EMA) or butyl methacrylates (BMA) at different ratios and coated on the inner surfaces of incubation vials. Our surface analysis showed that the amount of –COOH groups on the surface coatings was lower than the ratios of AA prepared in the materials even though the surface content of –COOH groups increased with increasing in AA ratios. It was indicated that the surface hydrophobicity increased with increasing alkyl chain length: –CH 3 > –CH2CH3 > –(CH2)3CH3, and decreased with increasing –COOH groups. No significant differences in surface hydrophobicity was found on surfaces with –CH3 and –CH2CH3 groups in the presence of –COOH groups. The material coating was as smooth as uncoated glass and without any major flaws. The average roughness of material-coated surface (3.99 ± 0.54 nm) was slightly higher than that of uncoated glass surface (2.22 ± 0.29 nm). However, no significant differences in surface average roughness was found among surfaces with the same functionalities at different –COOH ratios nor among surfaces with different alkyl groups but the same –COOH ratios. These suggested that the surface functional groups and their compositions had a combined effect on modulating surface hydrophobicity but not surface roughness.
The second part of our study was to investigate the effect of surface functional groups and their compositions on blood cascade activation and structural properties of the formed clots. It was found that surfaces with –COOH/–(CH2)3CH3 induced a faster coagulation activation than those with –COOH/–CH3 and –CH2CH3, regardless of the –COOH ratios. An increase in –COOH ratios on –COOH/–CH3 and –CH2CH3 surfaces decreased the rate of activation. Moreover, all material-coated surfaces markedly reduced the complement activation compared to uncoated glass surfaces, and the pattern of complement activation was entirely similar to that of surface-induced coagulation, suggesting there is an interaction between two cascades. The clots formed on material-coated surfaces had thicker fibrin with a tighter network at the exterior when compared to uncoated glass surfaces. Compared to the clot exteriors, thicker fibrins with a loose network were found in clot interiors. Coated surfaces resulted in more rigid clots with a significantly slower fibrinolysis after 1 h of lysis when compared to uncoated glass surfaces. Significant differences in fibrinolysis after 1 h of lysis among clots on material-coated surfaces correlated well with the differences in fibrin thickness and density at clot exterior. In addition, more growth factors were released during clot formation than during clot lysis. From an intact clot, there was a correlation between the amount of PDGF-AB release and fibrin density. Highest amount of PDGF-AB was released from clots formed on surfaces with 40% –COOH/60% –CH 3 (i.e. 65MMA). During clot lysis, the release of PDGF-AB also correlated with the fibrinolytic rate while the release of TGF-â1 was influenced by the fibrin thickness. This suggested that different clot structures led to different release profiles of growth factors in clot intact and degrading stages.
We further validated whether the clots formed on material-coatings provide the microenvironment for improved bone healing by using a rabbit femoral defect model. In this pilot study, the implantation of clots formed on 65MMA coatings significantly increased new bone formation with enhanced chondrogenesis, osteoblasts activity and vascularisation, but decreased inflammatory macrophage number at the defects after 4 weeks when compared to commercial bone grafts ChronOSTM â-TCP granules. Empty defects were observed when blood clot formation was inhibited.
In summary, our study demonstrated that surface functional groups and their relative ratios on material coatings synergistically modulate activation of blood cascades, resultant fibrin architecture, rigidity, susceptibility to fibrinolysis as well as growth factor release of the formed clots, which ultimately alter the healing microenvironment of injured bones.
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MacDonald, Shirley Lynn. "Modified haemoglobin as a blood substitute." Thesis, Heriot-Watt University, 1994. http://hdl.handle.net/10399/1360.
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Barlag, Rebecca Eileen. "Analytical Measurements in a Blood Substitute." University of Cincinnati / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100013078.
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Davies, Anna. "Platelet function in the presence of Synthocytes : a novel platelet substitute." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324048.
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Powanda, Doi Douglas. "Polyhemoglobin-superoxide dismutase-catalase blood substitute for ischemia-reperfusion in brain." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33826.
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Cerebrovascular disease, as manifested by stroke, is the most common acute neurological illness in the North America. The ischemic insult results in an interruption of blood flow to the central nervous system (CNS). Transient global cerebral ischemia-reperfusion is known to cause disruption of the blood-brain-barrier (BBB) and edema formation. Past investigations have indicated that following reperfusion, oxygen free radicals, superoxide in particular, are formed and played a major role in the development of neurological disorders and brain dysfunctions. The present first generation blood substitute consisting of a cross-linked hemoglobin (PolyHb) solution is useful for perfusing obstructed regions of vessels; however, this solution is not able to scavenge reactive oxygen radicals.Since our newly developed second-generation hemoglobin-based blood substitute, PolyHb cross-linked with superoxide dismutase and catalase (PolyHb-SOD-CAT), has the ability to scavenge reactive oxygen radicals, we hypothesize that this oxygen-carrying agent is able to deliver the required oxygen to brain tissue and remove the harmful oxygen free radicals in the same instance. In this investigation, we compare the physiological effects of this formulation with that of the first-generation hemoglobin-based blood substitute (PolyHb) on rat brain tissue using a 60-minutes transient global ischemia-reperfusion rat brain model.
Comparative molecular distribution was performed to observe the cross-linking process. Verifications of superoxide dismutase (SOD) and catalase (CAT) activity and oxygen-carrying property of PolyHb-SOD-CAT were also conducted. Tracking of cerebral water contents and colorimetric assay of Evans blue influx into brain tissue were used to evaluate the integrity of the blood-brain-barrier (BBB). This study shows that PolyHb-SOD-CAT can supply oxygen to ischemic tissues without causing reperfusion injury in a global stroke model.
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Ottarson, Alan. "The role of nitric oxide scavenging in hemoglobin-based oxygen carrier induced hypertension: systemic and microvascular effects." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3545.
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The purpose of this study was to identify the effects of a hemoglobin-based oxygen carrier, HBOC-201, on the cardiovascular system. Systemic cardiovascular parameters of mean arterial pressure (MAP), pulse pressure, heart rate, and oxygen saturation, as well as vascular resistance, were examined. A murine model of the cardiovascular system and microvasculature was employed. Sprague-Dawley rats (male; 230-530g; N = 13) were anaesthetised and surgically prepared for intravital microscopy of the spinotrapezius muscle. Increasing doses of HBOC-201 (2 mg/kg, 22 mg/kg, 230 mg/kg, and 780 mg/kg) and an iso-oncotic volume control were administered to assess for a dose-response relationship. MAP displayed a significant increase from baseline for both treatment groups, with no significant difference between the two. Arteriolar diameter displayed no changes from baseline, or between treatment groups or across doses. Based on these results, the noted changes in MAP were due to hypervolemia, and not a property of HBOC-201, itself.
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Keipert, Peter E. "Physiological effects of pyridoxylated polyhemoglobin solution as a blood substitute in rats." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=73967.
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D'Agnillo, Felice. "A novel red blood cell substitute based on crosslinked hemoglobin, superoxide dismutase, and catalase." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0024/NQ29915.pdf.
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Wong, Naomi Sie-Wan. "The Development of PolyHb-Fg: a novel blood substitute with the potential to support coagulation." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95667.
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Polyhemoglobin (polyHb) is one of the most promising blood substitutes in development It is awaiting approval from the FDA and has already been approved for routine surgical use in South Africa. Though it has been successful as an oxygen carrier, we have shown in the present study that with the lack of platelets and coagulation factors in the current polyHb formulations, there could be a risk of coagulation problems when large volumes ofpolyHb are administered. We therefore develop a novel blood substitute that would solve potential coagulation problems in a hemodiluted setting, while still being able to support oxygen transport. We developed polyhemoglobin-fibrinogen (polyHb-Fg), by crosslinking hemoglobin and fibrinogen with glutaraldehyde. Our in vitro tests showed that platelet aggregation was not potentiated by the addition ofpolyHb or polyHb-Fg. Using in vitro whole blood coagulation tests, hemodilution with polyHb adversely delayed the clotting mechanism. On the other hand a formulation ofpolyHb-Fg was able to achieve similar clotting times as whole blood, even with hemodilution. Thus, this formulation of polyHb-Fg has the potential for applications in the infusion of large volumes of blood substitute without interfering with coagulation.La polyhémoglobine (polyHb) est l'un des substituts du sang les plus prometteurs à l'étude. Ce composé attend l'approbation de la FDA et a déjà été approuvé pour l'usage chirurgical courant en Afrique du Sud. Bien que la polyHb ait connu un succès comme porteur de l'oxygène, nous avons montré dans la présente étude que le manque de plaquettes et des facteurs de coagulation dans les formulations courantes de polyHb, il pourrait y avoir un risque de problèmes de coagulation quand de grands olumes de polyHb sont administrés. Nous développons donc un nouveau substitut du sang qui résoudrait les problèmes potentiels de coagulation dans une situation d'hémodilution, tout en continuant d'assurer le transport de l'oxygène. Nous avons développé le polyhémoglobine-fibrinogène (polyHb-Fg), en réticulant l'hémoglobine et le fibrinogène avec du glutaraldéhyde. Nos essais in vitro ont prouvé que l'agrégation de plaquette n'a pas été augmentée par l'addition du polyHb ou du polyHb-Fg. Lors d'essais in vitro de coagulation de sang entier, l'hémodilution avec le polyHb retarde défavorablement le mécanisme de coagulation. D'autre part une formulation de polyHb-Fg permet d'obtenir un temp de coagulation semblable à celui du sang entier, même en cas d'hémodilution. Ainsi, cette formulation de polyHb-Fg a le potentiel requis pour des applications dans l'injection de grands volumes de produits de remplacement du sang sans interférer avec la coagulation.
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Elmer, Jacob James. "Expression, Purification, and Characterization of Mammalian and Earthworm Hemoglobins." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1321458620.
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Hionis, Veronique C. "The Effects of Hemoglobin-Based Oxygen Carriers On Mean Arterial Pressure, Arteriolar Diameter, and Nitric Oxide in the Microcirculation." VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd/1467.
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In the US today, blood transfusion is safer than ever. Nevertheless, the century-old quest for a suitable blood substitute persists. The elimination of unwanted side effects, especially transfusion-transmitted diseases, the problems and high cost factor involved in collecting and storing human blood, the pending worldwide shortages, and the need for compatibility testing are the driving forces contributing towards the development of blood substitutes. The leading research is focusing on hemoglobin-based oxygen carriers (HBOCs), which are limited in clinical application due to the pressor effect they induce. In this study, the mechanisms through which HBOCs affect mean arterial pressure (MAP), arteriolar diameter, and nitric oxide levels in the microcirculation were investigated, using Oxyglobin (HBOC-301), a third generation glutaraldehyde-polymerized bovine hemoglobin. The spinotrapezius muscle of female Sprague-Dawley rats was exteriorized for microcirculatory observations. HBOC in doses of 0.1, 1.0, 10.0, and 100.0 μM i.v., LNAME (30 mg/kg, i.v.), and papaverine (100 μM, topically) were given to the rat. Heparinized saline (0.1 ml and 0.5 ml, i.v.) served as control. MAP was monitored continuously through a cannula in the right carotid artery. Images of the feed, arcade and transverse arterioles were captured using a Zeiss Axioplan microscope, equipped with a digital camera, and imaging software. All doses of HBOC produced an overall vasoconstriction of the arterioles leading to an elevated MAP. Following L-NAME pretreatment, HBOC administration alone and with papaverine produced no significant elevation in MAP, indicating that the increase in resistance required basal amounts of nitric oxide (NO). This study concludes that the constriction of the arterioles correlated with the level of hypertension, and that these effects occur in a dose-dependent manner as a consequence of NO scavenging.
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Riha, Johanna. "Feasibility studies to inform a salt substitute intervention to lower blood pressure in rural Ugandan communities." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709032.
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Sallach, Rory Elizabeth. "Recombinant elastin-mimetic protein polymers as design elements for an arterial substitute." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/29614.
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Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2008.Committee Chair: Elliot Chaikof; Committee Member: Marc Levenston; Committee Member: Robert Nerem; Committee Member: Vincent Conticello; Committee Member: Yadong Wang. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Zhou, Yipin. "Synthesis and Biophysical Characterization of Polymerized Hemoglobin Dispersions of Varying Size and Oxygen Affinity as Potential Oxygen Carriers for use in Transfusion Medicine." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1321406529.
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Belcher, Donald Andrew. "Oxygenation of Solid Tumor Tissue Facilitated by Polymerized Human Hemoglobins." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu156294520544597.
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Magnan, Laure. "Développement, par ingénierie tissulaire, d’un substitut vasculaire entièrement biologique et humain grâce à l’utilisation d’une approche textile." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0284.
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Lorsque des vaisseaux autologues ne sont pas disponibles pour faire un pontage, des greffons synthétiques sont utilisés mais avec des taux d’échec élevés. En effet, malgré leurs bonnes propriétés mécaniques, la surface synthétique de ces greffons entraîne de la thrombose et de l’hyperplasie intimale ayant pour conséquence une mauvaise perméabilité du substitut à long terme pour de nombreuses applications. Par ingénierie tissulaire, des greffons vasculaires entièrement biologiques et humains ont déjà été produits par roulage de feuillets de matrice extracellulaire synthétisée par des fibroblastes dermiques humains in vitro. Grâce à une nouvelle méthode d’assemblage basée sur une approche textile, des greffons ont été produits trois fois plus rapidement. Pour ce faire, le feuillet a été découpé en fils afin de permettre la construction d’un substitut vasculaire par tissage. Cette thèse comporte trois articles. Le premier visait à montrer la composition riche de la matrice, décrire l’organisation de son réseau complexe de collagènes et démontrer que la dévitalisation par séchage de la matrice n’a pas affecté significativement cette organisation. Le deuxième avait pour but de décrire les propriétés mécaniques des fils en fonction du torsadage et/ou de l’âge de la matrice ainsi que l’effet sur la force de différents traitements nécessaires au processus de fabrication. Les différentes applications de l’approche textile dans la construction de structures complexes ainsi que les propriétés mécaniques des substituts tissés ont également été évaluées. Le troisième article a montré la faible réponse inflammatoire ainsi que le potentiel d’intégration et de remodelage de la matrice in vivo. Par ailleurs, la décellularisation n’a pas montré de résultats supérieurs à la dévitalisation, permettant ainsi de s’affranchir d’une étape de fabrication supplémentaire et potentiellement délétère à l’organisation biologique de cette matrice. En conclusion, cette thèse constitue la première démonstration de la fabrication de textiles humains mécaniquement très forts mais sans utilisation de matériel exogène. La dévitalisation couplée à l’approche textile ont permis de créer un modèle allogénique plus simple, plus rapide et moins coûteux mais avec un potentiel d’intégration in vivo intact. Ce modèle sera très prochainement étudié par implantation à long terme dans la circulation sanguineWhen autologous blood vessels are not available for bypass surgery, synthetic grafts are used but display high failure rates. Indeed, despite their good mechanical properties, their synthetic surface lead to thrombosis and intimal hyperplasia, which cause poor long-term patency in many applications. Using tissue engineering, completely biological and human vascular grafts have been produced by rolling sheets of extracellular matrix synthesized by dermal human fibroblasts in vitro. Using a new assembly technique based on a textile approach, grafts were produced three-time faster. To do so, sheets were cut into yarns to construct vascular substitute by weaving. This manuscript includes three articles. The first one aimed at showing the rich composition of the matrix, describing the organization of its complex network of collagens and demonstrating that the devitalization by drying the matrix did not significantly affect this organization. The second one described the mechanical properties of the yarns depending on the twisting, matrix age or different treatments useful for the manufacturing process. It also demonstrated some of the assembly techniques possible with this human yarn, as well as its possible use as a suture or to build a vascular graft. The third article showed the survival of the yarns subcutaneously implanted for 6 month in nude rats. The implants created little inflammatory response, were mildly remodeled and kept a significant mechanical strength. Decellularization did not show results improvement compared to the simple devitalization, demonstrating that the remaining cellular fragments were not a meaningful activator of the innate immune system. To conclude, this thesis is the first demonstration of the production of human textiles, without using any exogenous material and that are mechanically very strong. Both the devitalization and the textile approach have allowed to create a simpler allogeneic model, faster and cheaper but with an intact potential of integration in vivo, that will be studied very soon with a long-term implantation of the textile in the bloodstream
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Faivre, Béatrice. "Un transporteur d'oxygène a visée transfusionnelle : l'hémoglobine-dextran 10-benzène-tetracarboxylate évaluation préclinique chez le cobaye." Vandoeuvre-les-Nancy, INPL, 1993. http://www.theses.fr/1993INPL086N.
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L'hémoglobine conjuguée au dextran-benzène-tetracarboxylate (hb-dex-btc) est un transporteur d'O2 dont les objectifs sont de se substituer, de façon temporaire, à la fonction oxyphorique des hématies et de contribuer à la restauration de la volémie. Notre travail consiste à réaliser l'évaluation pharmaco-toxicologique de cette hémoglobine. Tout d'abord, nous présentons l'historique de la recherche sur les substituts du sang, la physiologie de l'hémoglobine dans le globule rouge et dans le plasma (structure, mécanismes d'oxygénation, d'oxydation, de réduction, catabolisme) ainsi que les principales modifications chimiques de l'hémoglobine et leurs résultats pharmacologiques. Par la suite, nous décrivons la préparation de la solution d'hb-dex-btc et nous réalisons l'étude pharmaco-toxicologique de celle-ci chez le cobaye a partir de chocs hémorragiques, d'échanges transfusionnels et d'intestins isolés. Ainsi, la demi-vie plasmatique de l'hb-dex-btc, son élimination urinaire, ses effets hémodynamiques, sa capacité à oxygéner l'organisme et à maintenir l'intégrité histologique de l'intestin sont déterminés. Pour finir nous étudions la stabilité de la molécule d'hb-dex-btc dans la circulation (auto-oxydation et dissociation). Dans ce travail, nous avons démontré la capacité de l'hb-dex-btc à assurer les deux fonctions principales du sang. Ce transporteur d'o2 permet d'obtenir des résultats similaires a deux présentés pour des hémoglobines actuellement en phase i du développement clinique
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Cunha, Armando dos Santos. "Emprego de veias preservadas em glicerol como substituto de enxerto de nervo: estudo experimental em ratos." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5158/tde-23012008-170513/.
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Grandes perdas de tecido neural não permitem a reparação por meio de anastomose primária. Nesses casos, a auto-enxertia de nervo é considerado o melhor tratamento. A despeito de um tratamento cirúrgico adequado, déficits funcionais são observados e melhoras quanto à recuperação funcional e diminuição das seqüelas são desejáveis. Várias são as técnicas que almejaram esse propósito. A interposição de condutores tubulares, como ponte entre os cotos proximal e distal do nervo seccionado, apresenta-se como uma técnica alternativa que oferece vantagens teóricas. A veia é um material estudado como possível condutor tubular avaliado experimentalmente e em casos clínicos. Estudos recentes têm dado importância na utilização de transplantes de tecidos armazenados em banco de tecidos. O glicerol é utilizado para preservação de tecidos, tendo sido relatado seu uso em nervos e vasos. Entretanto, não há relatos da utilização de veias preservadas em glicerol como substituto de enxerto de nervo. O objetivo deste trabalho foi comparar, em ratos, o grau de regeneração neural, utilizando análise histológica e análise funcional, obtida com a interposição de enxerto autógeno de nervo, veia autógena, veia autógena preservada em glicerol e veia alógena preservada em glicerol. Com técnica microcirúrgica, foram criados defeitos de 5 mm do nervo fibular de ratos da raça Lewis. Os animais foram divididos em quatro grupos de seis, de acordo com o tratamento empregado para correção do defeito: nos animais do Grupo A (grupo controle), foi realizado o reposicionamento do fragmento de nervo retirado (auto-enxerto); nos animais do Grupo B, foi interposto um segmento de 1 cm de veia jugular externa autógena; nos animais do Grupo C, foi interposto a veia jugular externa autógena preservada em glicerol a 98% a 4ºC por sete dias; no Grupo D os animais doadores foram ratos da raça Sprague-Dawley que tiveram a veia jugular externa preservada em glicerol de forma igual ao Grupo C e utilizadas para reconstrução do defeito neural em ratos da raça Lewis, sendo considerado um enxerto alógeno preservado em glicerol. Os animais foram sacrificados após seis semanas para realização dos estudos histológicos. Para a avaliação da recuperação funcional foram estudados os padrões de deambulação dos ratos (\"walking track analysis\") no pós-operatório imediato, 3 e 6 semanas de pós-operatório. O grupo controle (auto-enxerto) apresentou resultados histológicos semelhantes aos grupos de veias preservadas em glicerol (autógena e alógena), entretanto apresentou uma maior reação tecidual perineural e maior presença de escape axonal se comparada a todos os grupos. A utilização de veia autógena sem preservação demonstrou padrão histológico com maior neoangiogênese e áreas de rarefação axonal com presença de tecido conectivo no estroma neoformado. O padrão histológico foi semelhante nos demais grupos. O grupo que utilizou veia autógena (sem glicerol) apresentou menor recuperação funcional quando comparado com os demais grupos para 3 e 6 semanas. O resultado funcional foi estatisticamente semelhante entre os grupos de veias preservadas (autógena e alógena) e o auto-enxerto.Great losses of neural tissue cannot be repaired by primary conventional suturing. In such cases, nerve autografting is considered to be the treatment of choice. In spite of adequate surgical treatment, functional deficits occur. Also, improvement in functional recuperation and decrease in sequelae are expected. There are many techniques aiming at this purpose. The interposition of tubular conduits, as a bridge between the ends of a sectioned nerve, among these the vein graft, is an alternative technique which offers theoretical advantages. The vein is a studied material as possible evaluated tubular conductor experimentally and in clinical cases. Recent studies have given importance in the use of tissues transplants stored in banks. Glycerol is used for tissue preservation, having been told to its use in nerves and vessels. However, it does not have studies of the use of glycerol reserved veins in as substitute of nerve graft. The purpose of this study was to compare, in rats, the neural regeneration degree, using histological analysis and functional analysis, obtained after interposition of a nerve graft, autogenous vein, autogenous vein preserved in glycerol and allograft vein preserved in glycerol. A 5 mm neural gap in the fibular nerve of rats (Lewis breed) has been created under microsurgical techinique. Four groups of six animals each have been divided according to the treatment employed: Group A - control group: replacement of the fibular nerve itself (autograft); Group B - a 1omm segment of external jugular vein was interposed; Group C - a preserved external jugular vein in glycerol 98% per 7 days was interposed in the fibular nerve gap; Group D - external jugular vein preserved in glycerol of Sprague-Dawley rats had been used equal form to group C in Lewis rats. The animals had been sacrificed after 6 weeks for accomplishment of the histological studies. The functional walking track analysis was performed after in the pre-op, and in the pos-op (immediately, 3 and 6 weeks). The control group (autograft) presented similar histological results to the groups of glycerol preserved veins (autogenous vein and allograft vein), however it presented a bigger perineural tecidual reaction and bigger presence of escape axonal if compared with all the groups. The use of autogenous vein without preservation demonstrated histological results with greater neoangiogenesis and presence of connective tissue inside the neo-formed stroma. Histological pattern was similar to other studied groups. The group that used autogenous vein (without glycerol) presented little functional recovery for 3 and 6 weeks. No statistical difference was seen between groups A (autograft) and groups C and C(preserved veins) in the degree of functional recovery.
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Malet-Martino, Marie-Catherine. "La resonance magnetique nucleaire du fluor-19 appliquee a l'etude du metabolisme de medicaments fluores." Toulouse 3, 1986. http://www.theses.fr/1986TOU30204.
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Application de la spectrometrie rmn du fluor-19 a l'etude de la pharmacocinetique des fluoropyrimidines antitumorales (fluorouracil et doxifluridine), d'un antifongique (flucytosine) chez l'homme et du fluosol 43 chez la souris
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Chang, Wen-Hsiang, and 張文祥. "Polymerized Hemoglobin as Blood Substitutes." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/92600120220449355619.
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博士國立清華大學
化學工程學系
91
ABSTRACT Hemoglobin has been used as raw materials for manufacturing blood substitutes. However, because of its high oxygen affinity and short vascular retention time, limitations on hemoglobin as a blood substitute in clinical therapy have been reported in the literature. To decrease its oxygen affinity, hemoglobin has been modified by pyridoxylation (PLP-Hb) and followed by polymerization with glutaraldehyde. It was reported that the polymerized hemoglobin showed a P50 value of 19 to 22 mm Hg. Nevertheless, the reaction rate of hemoglobin with glutaraldehyde is too fast to control its molecular weight distribution. Additionally, the glutaraldehyde-polymerized hemoglobin is relatively unstable and may release glutaraldehyde residues during storage or sterilization. It was reported that glutaraldehyde is cytotoxic even at low doses. This may impair the biocompatibility of the polymerized products. In an attempt to overcome the aforementioned problems, two naturally occurring crosslinking agents, genipin and reuterin, were used by our group to polymerize hemoglobin. The first study was to investigate the feasibility of using genipin to polymerize hemoglobin as a blood substitute. The results indicated that the rate of hemoglobin polymerization by glutaraldehyde was significantly faster than that by genipin and it readily produced polymers with molecular masses greater than 500,000 daltons. It was found that the maximum degree of hemoglobin polymerization by genipin was approximately 40% if over-polymerization is to be prevented. With increasing the reaction temperature, hemoglobin concentration, and genipin-to-hemoglobin molar ratio, the duration taken to achieve the maximum degree of hemoglobin polymerization by genipin became significantly shorter. The P50 value of the unmodified hemoglobin was 9 mm Hg, while that of the genipin-polymerized PLP-hemoglobin increased to 21 mm Hg. It was found in a rat model that the genipin-polymerized PLP-hemoglobin increased the survive ratio of rats in a 50% blood exchange. The half-life of the unpolymerized hemoglobin in circulation was about 1.5 h, while that of the genipin-polymerized PLP-hemoglobin was approximately 12.5 h. In the second study, we used another naturally occurring crosslinking agent, reuterin, to polymerize hemoglobin. The results indicated that the rate of hemoglobin polymerization by reuterin was significantly slower than that by glutaraldehyde. In an animal study, it was found that animals transfused with the reuterin-polymerized PLP-hemoglobin up to a 50% blood exchange all survived (n = 6), while animals transfused with allograft plasma died in 3~5 h after transfusion (n = 6) and those transfused with phosphate buffered saline (pH 7.4, n = 6) and unpolymerized hemoglobin (n = 6) survived one out of six. The half-life of the unpolymerized hemoglobin in circulation was about 1.5 h, while that of the reuterin-polymerized hemoglobin was approximately 12 h. In conclusion, genipin and reuterin are promising agents to polymerize hemoglobin as blood substitutes.
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Page, Thomas Carey. "Oxygen transport by hemoglobin-based blood substitutes." Thesis, 1997. http://hdl.handle.net/1911/19193.
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A dual track approach has been applied to the study of oxygen transport behavior of erythrocyte/hemoglobin mixtures flowing in microvessels. The method includes experimental and theoretical modeling of the microcirculation. An experimental in vitro 27 $\mu$m diameter capillary model was developed to provide detailed oxygen flux measurements for homeglobin solutions, erythrocyte suspensions, and erythrocyte/hemoglobin solution mixtures. The experimental apparatus includes computerized data acquisiton and control coupled to a Leitz Toolmaker Microscope-based, dual wavelength microspectrophotomer. Fractional oxygen saturation may be determined for various axial positions, and the resulting experimental data have been shown to agree well with simulations calculated from previously developed theoretical models of oxygen transport in hemoglobin solutions and rbc suspensions. Direct comparison of hemoglobin solutions with rbc suspensions of the same overall hemoglobin concentration and oxygen affinity shows that hemoglobin solutions are more efficient transporters of oxygen. Experiments on polymerized hemoglobin suggests that some heme pockets may have not be available for oxygen transport. The quality and quantity of the experimental data represent a significant improvement over previous experimental designs, and the results confirm existing oxygen transport models.
Ultrapurified, native and polymerized bovine hemoglobin/red blood cell mixtures were studied in the capillary. Dose response plots were generated by varying the extracellular to intracellular hemoglobin distribution ratio. Increased extracellular hemoglobin concentration increased oxygen transport efficiency for both uptake and release. When only 10% of the total hemoglobin was extracellular, half of the increased efficiency of pure hemoglobin solutions was reached. When half the hemoglobin was extracellular, the mixtures behaved like hemoglobin solutions.
A mathematical model of the mixture experiments initially failed to fully predict the enhancement of oxygen uptake, but well described release experiments. Consideration of shear induced augmentation led to a new hypothesis for the relative importance of extracellular mixing in rbc/hemoglobin mixtures flowing in arteriolar sized conduits. The resulting semi-predictive model matches experimental data for a variety of conditions. This model may be used to predict performance of hemoglobin-based blood substitutes.
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Tsai, Lin-Wei, and 蔡令緯. "Hemoglobin Based Artificial Blood Substitutes Using Nanodiamond." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/86031550231972656847.
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碩士國立東華大學
物理學系
101
The basics material properties of nanodiamond (ND) are researched for many years. Nowadays, many groups want to apply this material in biomedical application using its advantages such as low cytotoxicity, intrinsic photoluminescence, sharp characteristic Raman signal, only carbon atoms composition and well-developed synthesis technologies. Due to these advantages, nanodiamond could be a potential material on cancer therapy and targeting drug delivery. Studying the ND potential for drug delivery, the first problem we would face is nanodiamonds large aggregation. We can observe it in buffer solution (Phosphate buffered saline, PBS as well as cell growth mediums) or blood plasma. In this work we use blood protein albumin (rat serum albumin, RSA) adsorbed on nanodiamonds surface to prevent the ND aggregation. This effect has been analyzed using UV-visible spectrometer to measure RSA adsorption on nanodiamonds. Particle size and -potential are measured using dynamic light scattering analyzer (DLS analyzer) to evaluate the size of aggregates and the surface charge of cND and cND-RSA complexes. If this method to decrease the aggregation is feasible, in the future it could be used in pre-clinical preparation of ND to prevent the side effects which can arise due to large size aggregation. In bio-medical applications nanodiamonds and their complexes have to be transported by blood circulation to reach the target tissues. If we want to apply any ND complexes in pre-clinical/ clinical studies, the second question we have to face is “does nanodiamonds affect the blood cells, first of all red blood cells (RBC) or not?” In this part of work, we used Raman spectroscopy to measure the oxygenation process of RBC. RBC’s function is to carry or release oxygen, which is bound by protein hemoglobin (Hb) contained in RBC. Hemoglobin conformation depends on oxygenation state and the structure and oxygenation state can be characterized by Raman spectroscopy. We use Raman spectroscopy to estimate the RBC function, using spontaneous oxygenation in the air oxygen-containing atmosphere and purging nitrogen for deoxygenation. Raman spectra were measured every five minutes and the changes of oxygen saturation was calculated using characteristic peaks of oxygenated or deoxygenated state to observe the effects of various treatments on the oxygenation/deoxygenation process. In the third part of work, we try to develop an oxygen carrier based on hemoglobin and cND-RSA, using rat hemoglobin. Using spectroscopic methods we analyzed its adsorption on ND and estimated the oxygenated and deoxygenated states of hemoglobin adsorbed on nanodiamonds surface. We show that 50 nm cND(RSA)-Hb can carry oxygen successfully, however, due to the complicate physiology condition, further use of this kind of oxygen carrier in-vivo needs more preliminary in-vitro investigations.
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Arifin, Dian Respati. "Cellular hemoglobin-based oxygen carriers as potential artificial blood substitutes." 2005. http://etd.nd.edu/ETD-db/theses/available/etd-05232005-205232/.
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Thesis (Ph. D.)--University of Notre Dame, 2005.Thesis directed by Andre F. Palmer for the Department of Chemical and Biomolecular Engineering. "May 2005." Includes bibliographical references (leaves 146-158).
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Kan, Pei, and 甘霈. "Separation and Purification of Hemoglobin as the Raw Material of Blood Substitutes." Thesis, 1996. http://ndltd.ncl.edu.tw/handle/95717985284184810047.
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Eike, Julie Hughes. "High oxygen affinity polymerized bovine hemoglobin-based oxygen carriers as potential artificial blood substitutes." 2005. http://etd.nd.edu/ETD-db/theses/available/etd-05202005-100650/.
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Thesis (Ph. D.)--University of Notre Dame, 2005.Thesis directed by Andre F. Palmer for the Department of Chemical and Biomolecular Engineering. "May 2005." Includes bibliographical references (leaves 122-135).
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Lui, Francine Evelyn. "Enhancing the Nitrite Reductase Activity of Modified Hemoglobin: Bis-tetramers and their PEGylated Derivatives." Thesis, 2011. http://hdl.handle.net/1807/31844.
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The need for an alternative to red cells in transfusions has led to the creation of hemoglobin-based oxygen carriers (HBOCs). However, evaluations of all products tested in clinical trials have noted cardiovascular complications, raising questions about their safety that led to the abandonment of all those products. It has been considered that the adverse side effects come from the scavenging of the vasodilator – nitric oxide (NO) by the deoxyheme sites of the hemoglobin derivatives. Another observation is that HBOCs with lower oxygen affinity than red cells release oxygen prematurely in arterioles, triggering an unwanted homeostatic response. Since the need for such a product remains critical, it is important to understand the reactivity patterns that contribute to the observed complications.
Various alterations of the protein have been attempted in order to reduce HBOC-induced vasoconstriction. Recent reports suggest that a safe and effective product should be pure, homogenous and have a high molecular weight along with appropriate oxygenation properties. While these properties are clearly important, vasodilatory features of hemoglobin through its nitrite reductase activity may also act as an in situ source of NO. It follows that HBOCs with an enhanced ability to produce NO from endogenous nitrite may serve to counteract vasoactivity associated with NO-scavenging by hemoglobin.
Here we characterize the effects of different protein modifications on the nitrite reductase activity of hemoglobin. We produced a variety of HBOCs that include cross-linked tetramers, polyethylene glycol (PEG) conjugates and bis-tetramers of hemoglobin. We report that the rate of NO production strongly depends on the conformational state of the protein, with R-state stabilized proteins (PEG-Hbs), exhibiting the fastest rates. In particular, we found that PEGylated bis-tetramers of hemoglobin (BT-PEG) exhibit increased nitrite reductase activity while retaining cooperativity and stability. Animal studies of BT-PEG demonstrated that this material is benign: it did not cause significant increases in systemic blood pressure in mice, the major side effect associated with existing HBOCs. BT-PEG exhibits an enhanced nitrite reductase activity together with sample purity and homogeneity, molecular size and shape, and appropriate oxygenation properties, characteristics of a clinically useful HBOC.
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Lin, Yen-lin, and 林延霖. "Peptide-polyethyleneglycol Hemoglobin as a Blood Substitute." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/83591441796104123193.
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碩士國立中正大學
化學工程研究所
91
Although the current blood supply is much safer due to the improved process of blood screening and testing, people are still concerned about the transmission of HIV or hepatitis virus via blood transfusion. The oxygen-carrying blood substitutes have been intensively studied and hemoglobin-based blood substitutes is most attractive and promising. Hemoglobin solution lacking 2,3-diphosphoglycerate (2,3-DPG) cannot release sufficient oxygen in human body. In this study, therefore, peptides composed of 7~11 amino acids was designed to act like 2,3-DPG, and was crosslinked to the outer structure of hemoglobin through Maleimide — polyethyleneglycol — N-hydroxysuccinimidyl (MAL-PEG-NHS). MAL was the functional group to crosslink with cysteine in the peptide, whereas NHS to crosslink between peptide-PEG and hemoglobin. The results of the oxygen dissociation curve demonstrated that peptide-modified hemoglobin has higher P50 value than unmodified hemoglobin. Hence the peptide-modified hemoglobin can, therefore, become a better product for the red cell substitutes.
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Lee, Wen-Long, and 李文龍. "Polymerization of Hemoglobin by Genipin as Blood Substitute." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/81494813122166358762.
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Tsai, Ching Hsuan, and 蔡靚璇. "Polymerization of Hemoglobin by Genipin for Blood Substitute." Thesis, 1996. http://ndltd.ncl.edu.tw/handle/98281214161793759646.
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Hu, Meighen, and 胡思元. "Dynamic Measurement System for Oxygen Saturation for Blood Substitute." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/96873164719099836461.
Full textAbstract:
碩士中原大學
醫學工程學系
87
The purpose of this research is to develop a dynamic measurement system for the oxygen saturation in blood substitute. The system is helpful to the development of blood substitute. A sensing probe was designed to carry out the measurement with blood substitute inside a conducting tube. Its working principle is similar to that of a pulse oximeter. Blood pulses were generated by pressing the rubber tube with an electromagnetic device. Light transmission of red and near infrared through the blood sample were measured while changing its oxygen saturation. The dissolved oxygen was monitored by an dissolved oximeter as a reference, and the related oxygen saturation was calculated by using the Hill''s equation. The oxygen saturation calculated from the light transmission was correlated to the value evaluated from the dissolved oximeter.
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Chen, Nai-Ming, and 陳乃鳴. "Characterization of Acetyl-Glutathione-Polyethyleneglycol Hemoglobin as a Blood Substitute." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/5bvvts.
Full textAbstract:
碩士國立中正大學
化學工程所
93
Because the public concern for the possible transmission of HIV or hepatitis virus via blood transfusion, the oxygen-carrying blood substitutes have been extensively studied and developed. Among various blood substitutes, hemoglobin-based blood substitutes are most promising. There are two protein structures of hemoglobin, R and T states. Hemoglobin has greater affinity for oxygen in R state than in T state. Inside the red blood cells (RBCs), 2,3-diphosphoglycerate (2,3-DPG) gifted with five negative charges binds to hemoglobin, stabilizing hemoglobin in T state and helping oxygen release from hemoglobin for the rest of tissues. Our goal is to crosslink hemoglobin with the 2,3-DPG-like molecule for better oxygen release. Glutathione (GSH) consisted of three amino acids presents in a substantial amount in cells, serving as an anitoxidant. In physiological condition, the net charge of glutathione is positive one, two negative charges from carboxylic groups and one positive charge from amino group. If we eliminate the positive charge in the amino group by acetylation, we can make acetylated GSH carries two negative charges, which may become a good oxygen modulator for hemoglobin. In this study, acetyl-GSH was crosslinked to the outer structure of hemoglobin through Maleimide— polyethyleneglycol—N-hydroxysuccinimidyl (MAL-PEG-NHS). MAL was the functional group to crosslink PEG with cysteine in GSH, whereas NHS is to crosslink PEG with lysines in hemoglobin. Our results show that the oxygen dissociation curve of hemoglobin crosslinked with acetyl-GSH-PEG shifts to the right as compared to the control. Although the reactivities with nitric oxide are similar between hemoglobin and acetyl-GSH-PEG-hemoglobin, the greater viscosity and particle size of PEG modified hemoglobin will exhibit a better blood vessel response due to the increase of endothelial nitric oxide release and the avoidance of extravascalation of hemoglobin.
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Chang, Kun Yu, and 張坤玉. "A Cross-Over Study on the Effects and Mechanisms of Sodium Restricted and Salt Substitute Diets on Blood Pressure." Thesis, 1993. http://ndltd.ncl.edu.tw/handle/20164751411616913460.
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YungHsu-Chan and 詹詠絮. "The feasibility of liposomes with cholesterol substituted by phytosterols and the effect of antihypertensive oligopeptides encapsulated in liposomes on blood pressure of spontaneously hypertensive rats." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/09351080049537964457.
Full textAbstract:
碩士輔仁大學
食品營養學系
91
Liposomes that are made up with multilamellar phosphobilayers have cell-membrane-like hollow sphere. Their special characteristics and structure can be used to encapsulate substances to transport and protect materials. The purpose of this study was to use phytosterols, such as β-sitosterol and stigmasterol, as a substitute for cholesterol in liposomes. Their physicochemical properties such as encapsulation efficiency (EE), stabilities of storage, pH, oxidization and pepsin were investigated to assess it possibility. Liposomes prepared with phytosterols or cholesterol exhibited higher encapsulation efficiency of bovine serum albumin (BSA) (EE: 24-36% and 28%, respectively) than those prepared without addition of sterols (EE: 19%). The EE of glucose in liposomes increased with the increasing level of cholesterol or phytosterols added in liposomes, but EE values were not so good as in BSA. In addition, EE of liposomes were increased with repeating dehydration-rehydration cycle in five times. Liposomes at pH 6 or 7 were most stable, irrespective of their sterol compositions. Liposomes storage at 4℃ had a higher residual percentage than those of storage at -20℃ or room temperature. Sterols-containing liposomes were more stable during long-term storage at various temperatures than sterol-free counterparts. Addition of sterols to liposomes was effective in decreasing the TBARS during storage periods, it effects was more markedly when α-tocopherol was added. Fatty acid compositions were comparable after storage, no matter what sterols or α-tocopherol were added or not. Liposomes containing cholesterol or phytosterols were effective in protecting encapsulated oligopeptide from pepsin digestion. Furthermore, Encapsulated oligopeptide in sterols-containing liposomes orally administrated to spontaneously hypertensive rats (SHR) lowered blood pressure slowly but sustainedly, and it blood pressure-lowering effect was similar to that induced by Captopril. The results indicated that replacing cholesterol with phytosterols in preparing liposomes is feasible and recommended.