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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Avaliação sistemática do uso do Dried Blood Spot para determinação de elementos químicos em sangue capilar visando estudos de biomonitoramento no Brasil / Systematic evaluation of the use of Dried Blood Spot for determination of chemical elements in capillary blood in order biomonitoring studies in Brazil

Caran, Nara da Cruz Carolli 24 March 2016 (has links)
A biomonitorização humana ou biomonitoramento (BH) é definido como a medida periódica de determinada substância química ou seu metabólito em fluidos biológicos, principalmente sangue e urina, de uma população com o objetivo de avaliar a exposição e os riscos à saúde. Tal método tem se tornado comum em países desenvolvidos, porém ainda é uma prática pouco utilizada no Brasil. Isso ocorre pela dificuldade de coleta, armazenamento e transporte das amostras, principalmente em regiões sem infraestrutura e de difícil acesso. Diante disso, alguns procedimentos alternativos de coleta de amostra vêm sendo propostos. Um destes procedimentos é o Dried Blood Spot (DBS) ou coleta e armazenamento de amostra em papel-cartão. Este método oferece uma série de vantagens sobre os procedimentos de coleta convencionais, principalmente por reduzir consideravelmente o volume de amostra coletada. Entretanto, pouco se sabe sobre a estabilidade dos analitos após a deposição da amostra no cartão e do risco de contaminação da amostra pelo substrato sólido. Além disso, procedimentos de extração dos analitos do papel, para posterior quantificação, ainda não estão totalmente estabelecidos. Neste sentido, o presente trabalho avaliou de forma sistemática o procedimento de coleta de sangue por DBS visando sua futura aplicação em programas de biomonitoramento no Brasil para determinação dos elementos químicos As, Cd, Cu, Hg, Mn, Pb, Se e Zn por espectrometria de massas com plasma indutivamente acoplado (ICP-MS). Para isso, no estudo foram utilizadas três diferentes marcas comerciais de cartão coletor: Whatman 903(TM), Munktell(TM), e DMPK-C(TM). Todas as marcas de cartão apresentaram baixas concentrações dos elementos químicos. Após a deposição da amostra no papel cartão verificou-se que a concentração dos elementos químicos manteve-se estável por um período de pelo menos 60 dias (temperatura ambiente e ao abrigo da luz). Foi otimizado o método de extração dos analitos do substrato, com melhor condição obtida após a imersão do papel (corte circular de diâmetro de 1/2´´) por 60 minutos em solução extratora (0,5% v/v HNO3 e 0,01% v/v Triton(TM) X-100) na proporção de 1:50 v/v, seguida de 10 segundos de agitação por vortex. Após a extração, a solução resultante contendo os analitos foi diretamente injetada no ICP-MS. Cabe também destacar que não foram observadas diferenças estatísticas nas concentrações dos elementos químicos com coleta de sangue da veia do antebraço (sangue venoso) ou do dedo (sangue capilar). Os resultados obtidos no presente estudo, devem contribuir para a implementação deste procedimento em análises de elementos químicos (biomonitoramento da população brasileira), principalmente considerando as dificuldades de coleta, armazenamento e transporte de amostras clínicas em nosso país por sua extensão territorial. Além disso, este procedimento pode facilitar estudos com populações vulneráveis e que vivem em áreas remotas e de difícil acesso. / Human biomonitoring or biomonitoring (BH) is defined as the measurement of a particular chemical or metabolites in biological fluids, especially blood and urine, in a population to assess the level of exposure and health risks. Human biomonitoring is a common activity in developed countries, but is still an uncommon practice in Brazil. It mainly occurs due to the difficulty of collection, storage and transport of samples, particularly in regions without infrastructure and difficult access. Therefore, some alternative procedures for sample collection have been proposed. One of the procedures is the Dried Blood Spot (DBS). This method offers distinct advantages over conventional sample collection procedures, including the reduced sample volume required for analysis. However, little is known about the stability of analytes after sample deposition on the card and the possible risk of sample contamination by the solid substrate. In addition, the extraction procedures of elements from the substrate surface before determination are not yet fully established. In this sense, the present study evaluated systematically the DBS blood collection procedure aiming at its future application in biomonitoring studies in Brazil to determine the chemical elements As, Cd, Cu, Hg, Mn, Pb, Se and Zn by inductively coupled plasma mass spectrometry (ICP-MS). For this, the study used three different brands of collecting cards: Whatman 903(TM), Munktell(TM), and DMPK-C(TM). All card brands presented low concentrations of chemical elements. After sample deposition on cardboard it was found that the concentration of chemical elements remained stable for at least 60 days (at room temperature and protected from light). It was optimized the method of analytes extraction from the substrate, with the best condition obtained after immersing the paper (circular cutting diameter of 1/2 \'\') for 60 minutes in an extraction solution containing 0,5% v/v HNO3 and 0,01% v/v Triton(TM) X-100 in the ratio 1:50 v/v, followed by 10 seconds of vortex. After extraction, the resulting solution containing the analytes was directly injected into the ICP-MS. It can also be pointed out that no statistical differences was found between the concentrations of elements determined in forearm vein blood (venous blood) and finger blood (capillary blood). Taken together, the results of the present study can contribute to the employment of the DBS procedure for the screening of chemical elements in the Brazilian population, especially considering the difficulties of collection, storage and transport of clinical specimens in our country. Moreover, studies in vulnerable populations living in remote areas and of difficult access should be simplified.
2

Exercício físico progressivo e equilíbrio ácido-base em sangue capilar

Brandão, Alexandre Fonseca 17 December 2010 (has links)
Made available in DSpace on 2016-08-17T18:39:46Z (GMT). No. of bitstreams: 1 4891.pdf: 1632573 bytes, checksum: b04ec9266cb36baa5931b37060461b26 (MD5) Previous issue date: 2010-12-17 / The analysis of gases and metabolites in arterial and venous blood reflects the condition of homeostasis of the organism and which instantaneous energy demand required, indicating how biological systems behave in front of some physical stress, including the variation of intensity and volume of physical activity performed. Reactions of these compounds maintenance of constant blood pH by neutralization and / or elimination of organic acids derived from the metabolism momentary. It was an objective method, minimally invasive, to evaluate the acid-base resulting from the progressive increase of physical exercise from 100μL of blood capillary. The methodology used was the Balke protocol for cycle ergometer adapted to the operational needs of the equipment Gas Analyzer Radiometer ABL 800. The progressive increase of the load was 50 by 50 Watts until voluntary exhaustion with collecting and analyzing samples of capillary blood. Volunteers are 13 active students (5 women and 8 men) and three amateur athletes UFSCar aged between 20 and 30 years 25 ± 2, and body mass index 24 ± 4. The results are presented in the acid base nomogram Siggaard-Andersen, developed by the pH values between 7.43 ± 0.02 and 7.35 ± 0.04, ABE (Excess Base Real) between 4.16 ± 1 44 and -7.75 ± 3.17 mmol / L, pCO2 between 35.48 ± 2.61 and 37.20 ± 4.67 mmHg and [HCO3-] between 24 and 17 ± 0.6 ± 2.2 mmol / L with analysis of statistical tools ANOVA and Student's t test. The concentration of gases and metabolites present in blood capillary, presents the characteristic behavior expected during graded exercise as the exponential increase of lactate concentration and pH of the linear decay. / A análise de gases e metabólitos, de sangue arterial e venoso, reflete a condição de homeostase instantânea do organismo e qual a demanda energética exigida, indicando como os sistemas biológicos se comportam frente a algum stress físico, entre eles a variação da intensidade e volume da atividade física executada. Reações destes analitos garantem a manutenção do pH sanguíneo através da constante neutralização e/ou eliminação dos ácidos orgânicos derivados do metabolismo momentâneo. Foi objetivo um método, minimamente invasivo, para avaliar o equilíbrio ácido base conseqüente do aumento progressivo do exercício físico a partir de 100μL de sangue capilar. A metodologia utilizada contempla o protocolo de Balke para ciclo ergômetro adaptado as necessidades operacionais do equipamento Analisador de Gases ABL 800 Radiometer. O incremento progressivo da carga foi de 50 em 50 Watts até a exaustão voluntária com coleta e análise das amostras de sangue capilar. Os voluntários são 13 universitários ativos (5 mulheres e 8 homens) e 3 atletas amadores da UFSCar com idade entre 20 e 30 anos 25±2, e índice de massa corporal 24±4. Os resultados são apresentados no nomograma ácido base de Siggaard- Andersen, desenvolvidos através dos valores de pH entre 7,43±0,02 e 7,35±0,04, ABE (Excesso de Base Real) entre 4,16±1,44 e -7,75±3,17 mmol/L, pCO2 entre 35,48±2,61 e 37,20±4,67 mmHg e [HCO3 -] entre 24±0,6 e 17±2,2 mmol/L com análise das ferramentas estatísticas ANOVA e Teste T de Student. A concentração dos gases e metabólitos, presentes no sangue capilar, apresenta comportamento característico ao esperado durante o exercício físico progressivo como o crescimento exponencial da concentração de lactato e o decaimento linear do pH.
3

Avaliação sistemática do uso do Dried Blood Spot para determinação de elementos químicos em sangue capilar visando estudos de biomonitoramento no Brasil / Systematic evaluation of the use of Dried Blood Spot for determination of chemical elements in capillary blood in order biomonitoring studies in Brazil

Nara da Cruz Carolli Caran 24 March 2016 (has links)
A biomonitorização humana ou biomonitoramento (BH) é definido como a medida periódica de determinada substância química ou seu metabólito em fluidos biológicos, principalmente sangue e urina, de uma população com o objetivo de avaliar a exposição e os riscos à saúde. Tal método tem se tornado comum em países desenvolvidos, porém ainda é uma prática pouco utilizada no Brasil. Isso ocorre pela dificuldade de coleta, armazenamento e transporte das amostras, principalmente em regiões sem infraestrutura e de difícil acesso. Diante disso, alguns procedimentos alternativos de coleta de amostra vêm sendo propostos. Um destes procedimentos é o Dried Blood Spot (DBS) ou coleta e armazenamento de amostra em papel-cartão. Este método oferece uma série de vantagens sobre os procedimentos de coleta convencionais, principalmente por reduzir consideravelmente o volume de amostra coletada. Entretanto, pouco se sabe sobre a estabilidade dos analitos após a deposição da amostra no cartão e do risco de contaminação da amostra pelo substrato sólido. Além disso, procedimentos de extração dos analitos do papel, para posterior quantificação, ainda não estão totalmente estabelecidos. Neste sentido, o presente trabalho avaliou de forma sistemática o procedimento de coleta de sangue por DBS visando sua futura aplicação em programas de biomonitoramento no Brasil para determinação dos elementos químicos As, Cd, Cu, Hg, Mn, Pb, Se e Zn por espectrometria de massas com plasma indutivamente acoplado (ICP-MS). Para isso, no estudo foram utilizadas três diferentes marcas comerciais de cartão coletor: Whatman 903(TM), Munktell(TM), e DMPK-C(TM). Todas as marcas de cartão apresentaram baixas concentrações dos elementos químicos. Após a deposição da amostra no papel cartão verificou-se que a concentração dos elementos químicos manteve-se estável por um período de pelo menos 60 dias (temperatura ambiente e ao abrigo da luz). Foi otimizado o método de extração dos analitos do substrato, com melhor condição obtida após a imersão do papel (corte circular de diâmetro de 1/2´´) por 60 minutos em solução extratora (0,5% v/v HNO3 e 0,01% v/v Triton(TM) X-100) na proporção de 1:50 v/v, seguida de 10 segundos de agitação por vortex. Após a extração, a solução resultante contendo os analitos foi diretamente injetada no ICP-MS. Cabe também destacar que não foram observadas diferenças estatísticas nas concentrações dos elementos químicos com coleta de sangue da veia do antebraço (sangue venoso) ou do dedo (sangue capilar). Os resultados obtidos no presente estudo, devem contribuir para a implementação deste procedimento em análises de elementos químicos (biomonitoramento da população brasileira), principalmente considerando as dificuldades de coleta, armazenamento e transporte de amostras clínicas em nosso país por sua extensão territorial. Além disso, este procedimento pode facilitar estudos com populações vulneráveis e que vivem em áreas remotas e de difícil acesso. / Human biomonitoring or biomonitoring (BH) is defined as the measurement of a particular chemical or metabolites in biological fluids, especially blood and urine, in a population to assess the level of exposure and health risks. Human biomonitoring is a common activity in developed countries, but is still an uncommon practice in Brazil. It mainly occurs due to the difficulty of collection, storage and transport of samples, particularly in regions without infrastructure and difficult access. Therefore, some alternative procedures for sample collection have been proposed. One of the procedures is the Dried Blood Spot (DBS). This method offers distinct advantages over conventional sample collection procedures, including the reduced sample volume required for analysis. However, little is known about the stability of analytes after sample deposition on the card and the possible risk of sample contamination by the solid substrate. In addition, the extraction procedures of elements from the substrate surface before determination are not yet fully established. In this sense, the present study evaluated systematically the DBS blood collection procedure aiming at its future application in biomonitoring studies in Brazil to determine the chemical elements As, Cd, Cu, Hg, Mn, Pb, Se and Zn by inductively coupled plasma mass spectrometry (ICP-MS). For this, the study used three different brands of collecting cards: Whatman 903(TM), Munktell(TM), and DMPK-C(TM). All card brands presented low concentrations of chemical elements. After sample deposition on cardboard it was found that the concentration of chemical elements remained stable for at least 60 days (at room temperature and protected from light). It was optimized the method of analytes extraction from the substrate, with the best condition obtained after immersing the paper (circular cutting diameter of 1/2 \'\') for 60 minutes in an extraction solution containing 0,5% v/v HNO3 and 0,01% v/v Triton(TM) X-100 in the ratio 1:50 v/v, followed by 10 seconds of vortex. After extraction, the resulting solution containing the analytes was directly injected into the ICP-MS. It can also be pointed out that no statistical differences was found between the concentrations of elements determined in forearm vein blood (venous blood) and finger blood (capillary blood). Taken together, the results of the present study can contribute to the employment of the DBS procedure for the screening of chemical elements in the Brazilian population, especially considering the difficulties of collection, storage and transport of clinical specimens in our country. Moreover, studies in vulnerable populations living in remote areas and of difficult access should be simplified.
4

Development and Validation of Bioanalytical Methods : Application to Melatonin and Selected Anti-Infective Drugs

Römsing, Susanne January 2010 (has links)
This thesis describes bioanalytical methods for measuring melatonin and some anti-infective drugs in biological fluids. Solid-phase extraction (SPE) or protein precipitation was used for enrichment and purification of the analytes and Liquid Chromatography (LC) was used to analyze the samples. Developed methods were validated according to international guidelines. Melatonin is a hormone secreted by the pineal gland with a robust circadian rhythm. Bioanalytical methods for determination of melatonin in plasma and saliva have been developed which were used for monitoring melatonin levels in volunteers and patients suffering from sleep related diseases. Eflornithine (DFMO) is a chiral drug used for the treatment of human African trypanosomiasis. A bioanalytical method for determination of the DFMO enantiomers in plasma, after precolumn derivatization with o-phtalaldehyde and N-acetyl-L-cystein has been developed. The method has been used to study the L- and D-DFMO pharmacokinetics, in order to investigate the possible development of an oral treatment of DFMO. A method for simultaneous determination of three antiretroviral drugs i.e. Lamivudine (3TC), Zidovudine (AZT) and Nevirapine (NVP) in dried blood spots (DBS) was developed. The method was used for drug determination in two subjects after receiving standard antiretroviral treatment. The method seemed well suitable for the determination of 3TC and NVP and in some extent for AZT. Lumefantrine (LF) is one of the active components in a new fixed drug combination recommended by the WHO as a replacement to older drugs that has lost their effect. A method for the determination of LF in DBS was developed. The method is suitable for monitoring of drug treatment in rural settings. Tafenoquine is a new promising antimalarial drug under development. A method for the determination of Tafenoquine in plasma and in DBS is described. The method may be useful in future clinical studies in laboratory environment as well as in rural settings. / Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 703
5

Hållbarhet på kapillära blodprover för analys av hemoglobin, leukocyter och trombocyter / Shelf life for analysis of haemoglobin, leukocytes and platelets in capillary blood samples

Johansson, Sara January 2022 (has links)
Inom klinisk verksamhet är det av stor betydelse att känna till hållbarheten på olika analyter för att säkerställa att analysen inte genomförs på för gamla prover. Vid litteratursökning framgick att bland de publicerade studier som undersökt hållbarheten på blodprover har de flesta undersökt hållbarheten på venösa men inte kapillära blodprover. En vanligt förekommande analys med både venösa och kapillära prover är blodstatus, som inkluderar bland annat bestämning av hemoglobinkoncentrationen (Hb-), leukocyt- samt trombocytpartikelkoncentrationen (LPK och TPK). Analys av blodets celler kan ge allmän information om hälsotillståndet hos patienter och är därav viktiga och vanligt förekommande analyser. Syftet med examensarbetet var att undersöka hållbarheten för analyserna Hb, LPK och TPK på kapillära blodprover efter fyra och sex timmars förvaring i rumstemperatur. Provmaterialet utgjordes av 100 kapillära prover som analyserades på hematologiinstrumentet Sysmex XN-10. Analysmetoden för Hb var fotometri med natriumlaurylsulfat- (SLS-) metoden. LPK bestämdes med flödescytometri medan TPK bestämdes med impedansmetoden alternativt flödescytometri. Resultatet visade att det för Hb inte förekom någon signifikant statistisk skillnad mellan den initiala analysen och efter fyra respektive sex timmar. Analysresultatet för Hb var därmed stabilt under förhållandena i denna studie. För LPK och TPK förekom statistiskt signifikanta skillnader mellan resultatet vid den initiala analysen jämfört med efter fyra respektive sex timmar. Analysresultaten för LPK och TPK var därmed inte lika stabila som Hb är under förhållandena i studien. Den statistiska skillnaden bedömdes däremot inte ha någon klinisk betydelse, vilket ledde till slutsatsen är att kapillära prover för analys av Hb, LPK och TPK är hållbara i sex timmar vid förvaring i rumstemperatur. / One important factor in clinical practice is understanding the stability of analytes and for how long blood samples can be stored before analysis. Most published studies are based on venous blood samples rather than capillary. The knowledge about storage time for cells in capillary blood is therefore limited. Plenty of information can be obtained by analysing the blood cells and its components, including haemoglobin, white blood cells and platelets. These analyses are therefore some of the most common in clinical practice. The aim of this study was to evaluate the effect of the analysis result for haemoglobin, white blood cells and platelets in capillary blood samples after storage at room temperature for four and six hours, respectively. In the study, 100 capillary samples from anonymous patients were analysed with the haematology analyser Sysmex XN-10. The method for analysing haemoglobin was the sodium lauryl sulphate (SLS) detection method with spectrophotometry. White blood cells were analysed with fluorescens flow cytometry. Platelets were analysed with either impedance or fluorescens flow cytometry. The result of the study showed no statistically significant difference between the initial analysis results in haemoglobin and at four and six hours, concluding that within the conditions of this study, the analysis result for haemoglobin was stable. Significant statical differences were identified for both white blood cells and platelet analysis results at four and six hours. However, the identified statistical significance was not esteemed to have any clinical relevance. In conclusion haemoglobin, white blood cells and platelets in capillary blood can be stored for at least six hours at room temperature.
6

Cellular and molecular mechanisms of neurovascular coupling in the retina

Villafranca-Baughman, Deborah 01 1900 (has links)
Cette thèse de doctorat englobe deux projets majeurs visant à étudier l'interaction entre les nanotubes à effet tunnel inter-péricytes (IP-TNT), le couplage neurovasculaire et la modulation des cellules gliales dans le contexte du glaucome. Le premier projet se concentre sur la caractérisation et l'importance fonctionnelle des IP-TNT dans la régulation du couplage neurovasculaire, tandis que le second projet explore le rôle des cellules gliales, en particulier S100Β, dans la modulation des réponses des péricytes pendant l'hypertension oculaire (HTO), un facteur de risque important pour le développement du glaucome. Dans le premier projet, nous avons étudié la présence et les implications fonctionnelles des IP-TNT dans l'unité neurovasculaire. Grâce à des techniques d'imagerie avancées et à des expériences d'imagerie en direct chez la souris, nous avons visualisé et caractérisé ces nanotubes à effet tunnel qui relient les péricytes voisins dans la rétine. Nous avons découvert que les IP-TNT jouent un rôle crucial en facilitant la communication intercellulaire et la signalisation calcique entre les péricytes. Ces nanotubes contribuent à la régulation du flux sanguin capillaire et au couplage neurovasculaire, assurant l'apport efficace d'oxygène et de nutriments aux neurones actifs. Nos résultats mettent en lumière les interactions cellulaires complexes au sein de l'unité neurovasculaire et élargissent notre compréhension des mécanismes qui sous-tendent le couplage neurovasculaire. Dans le second projet, nous nous sommes concentrés sur le rôle des cellules gliales, en particulier la protéine S100Β qui se lie au calcium, dans la modulation des réponses des péricytes au cours de l'HTO, une caractéristique pathologique clé du glaucome. Grâce à une combinaison d'expériences in vivo, d'analyses moléculaires et de techniques d'imagerie, nous avons étudié l'impact de la S100Β sur les niveaux de calcium des péricytes et sur le flux sanguin capillaire. Nous avons observé que la S100Β est régulée à la hausse dans les cellules gliales, y compris les cellules de Müller et les astrocytes, au cours de l'HTO. L'administration de la protéine recombinante exogène S100Β a exacerbé l'influx de calcium intra-péricyte et altéré le flux sanguin capillaire, tandis que le blocage de la fonction S100Β a amélioré les niveaux de calcium des péricytes et rétabli un flux sanguin basal. La neutralisation de la S100Β a également protégé les cellules ganglionnaires de la rétine de la mort induite par l'HTO. Ces résultats mettent en évidence le rôle critique des cellules gliales et de la S100Β dans les déficits du couplage neurovasculaire au cours du glaucome, et donnent un aperçu des cibles thérapeutiques potentielles pour préserver la santé et la fonction de la rétine. Collectivement, les résultats des deux projets contribuent à notre compréhension de l'interaction complexe entre les IP-TNT, le couplage neurovasculaire et la modulation des cellules gliales dans le contexte du glaucome. En élucidant le rôle des IP-TNT dans la régulation neurovasculaire et l'impact des cellules gliales, en particulier la S100Β, sur les réponses des péricytes, cette thèse fournit des informations précieuses sur les mécanismes sous-jacents de la pathogenèse du glaucome. Ces résultats peuvent ouvrir la voie au développement de stratégies thérapeutiques innovantes ciblant les IP-TNT et la modulation médiée par les cellules gliales afin de préserver la fonction rétinienne et de prévenir la perte de vision dans le glaucome et les maladies neurodégénératives associées / This PhD thesis encompasses two major projects aimed at investigating the interplay between interpericyte tunneling nanotubes (IP-TNTs), neurovascular coupling, and glial cell modulation in the context of glaucoma. The first project focuses on the characterization and functional significance of IP-TNTs in neurovascular coupling regulation, while the second project explores the role of glial cells, particularly S100Β, in modulating pericyte responses during ocular hypertension (OHT), an important risk factor for developing glaucoma. In the first project, we investigated the presence and functional implications of IP-TNTs in the neurovascular unit. Through advanced imaging techniques and live imaging experiments in mice, we visualized and characterized these tunneling nanotubes connecting neighboring pericytes in the retina. We found that IP-TNTs play a crucial role in facilitating intercellular communication and calcium signaling between pericytes. These nanotubes contribute to the regulation of capillary blood flow and neurovascular coupling, ensuring the efficient delivery of oxygen and nutrients to active neurons. Our findings shed light on the intricate cellular interactions within the neurovascular unit and expand our understanding of the mechanisms underlying neurovascular coupling. In the second project, we focused on the role of glial cells, specifically the calcium-binding protein S100Β, in modulating pericyte responses during OHT, a key pathological feature of glaucoma. Through a combination of in vivo experiments, molecular analyses, and imaging techniques, we investigated the impact of S100Β on pericyte calcium levels and capillary blood flow. We observed that S100Β is upregulated in glial cells, including Müller cells and astrocytes, during OHT. Administration of recombinant S100Β protein exacerbated intrapericyte calcium influx and impaired capillary blood flow, while blocking S100Β function improved pericyte calcium levels and restored normal blood flow. Notably, S100Β neutralization also protected retinal ganglion cells from OHT-induced death. These findings highlight the critical role of glial cells and S100Β in neurovascular coupling deficits during glaucoma, providing insights into potential therapeutic targets for preserving retinal health and function. Collectively, the results from both projects contribute to our understanding of the complex interplay between IP-TNTs, neurovascular coupling, and glial cell modulation in the context of glaucoma. By elucidating the role of IP-TNTs in neurovascular regulation and the impact of glial cells, particularly S100Β, on pericyte responses, this thesis provides valuable insights into the underlying mechanisms of glaucoma pathogenesis. These findings may pave the way for the development of innovative therapeutic strategies targeting IP-TNTs and glial cell-mediated modulation to preserve retinal function and prevent vision loss in glaucoma and related neurodegenerative diseases
7

Feasibility, acceptability, and safety of a novel device for self-collecting capillary blood samples in clinical trials in the context of the pandemic and beyond

Dasari, Harika 12 1900 (has links)
Introduction: Les dispositifs d'auto-prélèvement sanguin permettent des échantillonnages à distance. L'étude explore (i) l'influence des sites de prélèvement et de l'analgésie topique sur le volume sanguin capillaire et la douleur, et (ii) la faisabilité, la sécurité et l'acceptabilité de l'autoprélèvement capillaire avec le dispositif Tasso-SST chez les adultes et les enfants. Méthodes: L'étude comportait deux phases avec la phase expérimentale comprenant deux études transversales conduit sur place, chez des adultes en santé (> 12 ans) et enfants (< 18 ans) en dyades enfant-parent. Les issues principales étaient: le volume capillaire sanguin et la perception de la douleur. La phase de mise en oeuvre portait sur deux essais multicentriques et ciblait les participants ayant opté pour des visites à distance. L’issu principal était le volume capillaire sanguin. Les issues secondaires des études incluaient l’échec du dispositif, les événements indésirables, la satisfaction et la volonté de réutiliser le dispositif. Résultats: L'étude a recruté 90 adultes et 9 enfants avec 7 parents (dyades) dans la phase expérimentale et 15 adultes et 2 enfants en phase de mise en oeuvre. Durant la phase expérimentale chez l'adulte, le dispositif a collecté une médiane (25%, 75%) de 450 (250, 550) μl de sang, sans différence significative entre les sites de ponction et l'usage ou non d’analgésie topique. L'analgésie topique a réduit la perception de la douleur de 0,61 (IC à 95 %: 0,97, 0,24 ; P <0,01) points sur l'échelle de 11 points, avec une réduction plus importante au bas du dos. Le volume médian collecté chez les enfants était de 450 μl avec un score médian de douleur de 0,5. En combinant toutes les études et phases, le volume médian collecté était de 425 (250, 500) μl, avec un taux d’échec de 4,4 % et des effets indésirables mineurs signalés chez 8,9 % des participants. Tous étaient prêts à réutiliser l'appareil. Conclusion: L'auto-prélèvement capillaire, avec un rendement d’un peu moins de 500 μl, est peu douloureux avec un bon profil d’innocuité, un haut degré de satisfaction et peu d'échec chez les adultes et les enfants. Le site de ponction et l'analgésie topique n'influent pas significativement sur le volume sanguin. L'utilisation d'une analgésie topique au bas du dos réduit légèrement la douleur, mais l’importance clinique de la réduction reste incertaine. / Introduction: Blood self-collection devices offer an opportunity to provide remote sampling. The study aimed to explore (i) the impact of puncture sites and topical analgesia on capillary blood volume and pain perception and (ii) the feasibility (volume, failure rate), safety, and acceptability of capillary self-collection using the Tasso-SST blood collection device among adults and children. Methods: The study consisted of two phases, with the investigational phase involving on-site cross-sectional studies in healthy adults (>12 years) and children (<18 years) as child-parent dyads. The primary outcomes were capillary blood volume and pain perception. The implementation phase involved two multicentre trials in participants opting for remote visits. Where the primary outcome was blood volume. Secondary outcomes of the study included device failure, adverse events, satisfaction, and willingness to re-use the device. Results: The study enrolled: 90 adults and 9 children with 7 parents (dyads) in the investigational phase and 15 adults and 2 children in the implementation phase. During the adult investigational phase, the device collected a median of 450 (interquartile range: 250, 550) μl of blood with no significant difference between puncture sites and topical analgesia. Topical analgesia reduced pain perception by 0.61 (95% CI: 0.97, 0.24; P <0.01) points on the 11-point scale, with a magnitude of reduction varying by puncture site, with the lower back showing the most decrease. The median volume collected among children in the dyads was 450 (400, 475) μl with a median pain score of 0.5. During the implementation phase, both participants and research staff expressed willingness to use the device again. Overall, combining all studies and phases, the median volume collected was 425 (250, 500) μl, and the device failure rate was 4.4%; minor adverse effects were reported in 8.9% of the participants, all were willing to use the device again. Conclusion: Capillary blood self-collection, yielding slightly less than 500 μl, proves to be minimally painful with a good safety profile, high satisfaction, and low failure rates for both adults and children. The puncture site and topical analgesia don't significantly affect blood volume, but using topical analgesia on the lower back slightly reduces pain, with unclear clinical importance.

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