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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.
381

Validação da escala de pensamentos castróficos e associação do catastrofismo com marcadores biológicos

Sehn, Francislea Cristina January 2012 (has links)
Base teórica: A dor crônica decorre de alterações estruturais e funcionais mal adaptativas que influenciam a resposta ao estímulo ou que sustentam os processos de excitabilidade. Um dos sintomas que permeia grande número de pacientes com dor crônica é a catastrofização, cujas características são um conjunto de pensamentos negativos, deseperança e magnificação do sintoma ou condição. Este sintoma é mensurado por meio de uma escala de catastrofização usada em vários países. No entanto não dispomos deste instrumento validado para o português.Objetivos: Validar para o português do Brasil (B) a PCS e verificar suas propriedades psicométricas. Verificar a consistência interna, estrutura fatorial, e sua capacidade de discriminar pacientes com condições específicas de dor crônica como cefaleia tensional crônica (CTC) (International Headache Society) e fibromialgia de acordo com os critérios do American College of Rheumatology. Avaliar os possíveis mecanismos neurobiológicos correlacionados com o nível de sintomas catastróficos, através de dosagens de cortisol e TNF em uma amostra de pacientes com CTC. Métodos: 384 sujeitos com idades entre 18-79 anos com dor crônica de origem músculo-esquelética participaram deste estudo transversal. A versão da B-PCS foi aplicada, assim como a intensidade da dor, interferência da dor na capacidade funcional, no humor e um questionário sócio-demográfico. A capacidade discriminatória da B-PCS foi avaliada numa sub-amostra de pacientes com cefaléia tensional crônica (CTC) de acordo com os critérios da International Headache Society (n = 19), e em outro com diagnóstico de fibromialgia segundo os critérios do American College of Rheumatology (n = 50). Após a validação a B-PCS foi aplicada num grupo de pacientes com CTC. Foi avaliado o impacto da cefaleia usando o Short-Form Headache Impact Test (HIT-6), coletadas amostras de cortisol salivar às 08:00; 16:00 e 22:00 e dosado o TNF sérico. Resultados: Observou-se boa consistência interna [valores α de Cronbach de 0,91 para o total da BR-PCS. Para os subdomínios 0,93 (desesperança), 0,88 (magnificação), 0,86 (ruminação)]. Os coeficientes de correlação item-total variaram 0,91-0,94. Análise fatorial confirmatória apoiou os três fatores de estrutura, com o índice de ajuste comparativo = 0,98, a raiz quadrada média do erro de aproximação = 0,09, e índice de ajuste normalizado = 0,98. Foram encontradas correlações significativas para a intensidade da dor, interferência da dor e humor do paciente (coeficientes de correlação variaram 0,48-0,66, P <0,01). Nas comparações entre grupo controle (pacientes com escores de dor na VAS igual ou inferior a 40 mm na maior parte do dia nos últimos seis meses), e pacientes com condições dolorosas específicas observou-se pontuações mais baixas de catastrofização no grupo controle. No grupo com CTC a relação entre a curva de cortisol salivar, obtida em três pontos do dia (08:00, 16:00 e 22:00 horas) e a catastrofização de acordo com os grupos de catastrofização ( escores B-PCS) estratificados em níveis alto e baixo (alto> Q75 = 42 ou baixo Q75 < 42 ), utilizou-se análise de variância de medidas repetidas (ANOVA), com teste post hoc de Bonferroni. Pacientes com altos escores de catastrofismo apresentaram supressão da secreção de cortisol às 08:00 (p <0,05). Usando modelo multivariado de regressão linear, os fatores correlacionados positivamente com a variável dependente (escores da B-PCS) foram os fatores independentes: níveis séricos de TNF, pontuação no HIT6 e idade (p <0,05). O uso de antidepressivos reduziu em 21% o incremento nos escores da B-PCS. Conclusão: Nossos resultados suportam a validade e confiabilidade da B-PCS. A escala mostrou propriedades psicométricas satisfatórias. A estrutura de três fatores apresentou boas propriedades discriminatórias na comparação de pensamentos catastróficos de sujeitos controles, fibromiálgicos e CTC. A B-PCS mostrou-se instrumento com perfil satisfatório para uso em pesquisa e clínica no Brasil. Também, observamos que a catastrofização está correlacionada com o impacto da CTH, menor oscilação circadiana na secreção de cortisol salivar e níveis séricos de TNF. Isto sugere que o comportamento catastrófico possui substrato biológico que indica sua associação com o estresse crônico e resposta inflamatória. / Theoretical basis: Chronic pain is due to structural and functional changes that influence the maladaptive response to stimuli or processes that underlie excitability. One of the symptoms that permeates large number of patients with chronic pain is the catastrophizing, whose characteristics are a set of negative thoughts, holplessness and magnification of the symptom or condition. This symptom is measured through a catastrophizing scale used in several countries. However, we do not have this instrument for the Portuguese. Objectives: To validate the PCS for Brazil’s Portuguese (B) and verify its psychometric properties. Check the internal consistency, factor structure, and its ability to discriminate patients with specific conditions of chronic pain chronic such as chronic tension type headache (CTH) in accordance with International Headache Society and fibromyalgia according to the criteria of the American College of Rheumatology. To evaluate the possible neurobiological mechanisms correlated with the level of catastrophic symptoms through Cortisol and TNF dosages in a sample of patients with CTH. Methods: 384 subjects aged 18-79 years with chronic musculoskeletal pain participated in this cross-sectional study. The version of the B-PCS was applied as well as pain intensity, pain interference in functional ability, mood and a socio-demographic questionnaire. The discriminatory capacity of B-PCS was assessed in a subsample of patients with chronic tension type headaches (CTH) in accordance with the criteria of the International Headache Society (n = 19), and another with a diagnosis of fibromyalgia according to the criteria of the American College of Rheumatology (n = 50). After the validation the B-PCS was applied in a group of patients with CTH. The impact of headache were evaluated using the Short-Form Headache Impact Test (HIT-6), salivary cortisol samples collected at 08:00, 16:00 and 22:00 and serum TNF. Results: There was good internal consistency [Cronbach's α values of 0.91 for the total PCS-BR. For subdomains 0.93 (holplessness), 0.88 (magnification), 0.86 (rumination)].The coefficients of item-total correlation ranged from .91 to .94. Confirmatory factor analysis supported the three factor structure, with the comparative fit index = 0.98, root mean square error of approximation = 0.09, standard setting and the index of = 0.98. Significant correlations were found for pain intensity, pain interference and mood of the patient (correlation coefficients ranged from .48 to .66, P <0.01). Comparisons between the control group (patients with VAS pain scores at or below 40 mm in most of the day in the last six months), and patients with specific pain conditions were observed lower catastrophizing scores in the control group. In the group with CTH the relationship between the salivary cortisol curve, obtained at three points of the day (08:00, 16:00 and 22:00 hours) and catastrophizing according catastrophizing groups (B-PCS scores) stratified into low and high level (high>Q75=42 or low Q75<42), we used analysis of variance for repeated measures (ANOVA) with Bonferroni post hoc test. Patients with high scores of catastrophism had suppression of cortisol secretion at 08:00 (p <0.05). Using a multivariate linear regression model, the factors positively correlated with the dependent variable (scores of B-PCS) were the independent factors: serum levels of TNF, HIT6 score and age (p <0.05). The use of antidepressants decreased by 21% the increase in scores of B-PCS. Conclusion: Our results support the validity and reliability of the B-PCS. The scale showed satisfactory psychometric properties. The three-factor structure showed good discriminatory properties in comparison to control subjects, fibromyalgia, and HSC catastrophic thoughts. The B-PCS showed to be an instrument with a profile suitable for use in research and clinical practice in Brazil. Also, we found that catastrophizing is correlated with the impact of CTH, lower circadian oscillation in the secretion of salivary cortisol and serum levels of TNF. This suggests that the catastrophic behavior has biological substrate indicating its association with chronic stress and inflammatory response.
382

Marcadores inflamatórios no comprometimento cognitivo leve amnéstico : estudo caso-controle

Rizzi, Liara January 2014 (has links)
Introdução: A Doença de Alzheimer (DA) é uma desordem neurodegenerativa e a forma mais comum de demência. Processos inflamatórios parecem desempenhar importante papel na fisiopatologia da DA. A neuroinflamação é caracterizada pela ativação da microglia e a liberação de citocinas inflamatórias, tais como IL-1β, IL-6 e TNF-α. Porém, não se sabe qual é a real contribuição destes marcadores inflamatórios no desenvolvimento da DA. Objetivos: A proposta deste estudo é avaliar a possível relação entre marcadores inflamatórios no liquido cefalorraquidiano de indivíduos com comprometimento cognitivo leve amnéstico (CCL-a), com 60 anos ou mais, e comparar com controles saudáveis da mesma faixa etária. Métodos: Foram examinadas as concentrações de IL-1β, IL-6 e TNF-α no líquido cefalorraquidiano de sujeitos com CCL-a e em controles pelo método ELISA. Diagnósticos de CCL-a foram baseados na anamnese e nos critérios de Petersen, corroborados pela escala CDR. Para avaliar a função cognitiva o teste de memória e reconhecimento de palavras do CERAD e o Teste do Relógio foram aplicados aos participantes. Para a avaliação de sintomas depressivos usou-se o GDS. Resultados: Este estudo demonstrou diminuição significativa nos níveis de IL-1β (13.735 vs 22.932 pg/mL; p <0.001) e TNF-α (1.913 vs 2.627 pg/mL; p: 0.002), mas não nos níveis da IL-6 (4.178 vs 5.689 pg/mL; p: 0.106), entre casos e controles. Indivíduos com IL-1β < 17 pg/mL possuem 7.2 (CI: 1.5-36; p: 0.016) mais chances de evoluírem à CCL-a. Além disso, houve correlação positiva entre IL-1β e a pontuação da lista de palavras do CERAD (rs: 0.299; p: 0.046). A análise de regressão linear mostrou que os níveis de IL-1β podem explicar 13.7% (β: 24.545; p: 0.012) da variância da pontuação do CERAD, o que sugere uma dependência linear direta. Conclusões: A neuroinflamação, mediada pela IL-1β e pelo TNF-α, provavelmente possui importante papel na prevenção de CCL-a. / Introduction: Alzheimer Disease (AD) is a neurodegenerative disorder and the most common form of dementia. Inflammatory processes may play a significant role at the pathophysiology of AD. Neuroinflammation is characterized by activation of microglia and the release of inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. Although, it is unknown what is the real contribution of these inflammatory markers in the development of AD. Aims: The purpose of this study is to assess the possibly relationship between inflammatory markers in CSF of amnestic MCI subjects, with sixty years or older, and compare to aged healthy controls. Methods: We examined concentrations of IL-1β, IL-6 and TNF-α at CSF of amnestic MCI subjects and controls by ELISA. MCI diagnoses were based on anamnesis and Petersen criteria, corroborated by CDR. To assess the cognitive function the word list memory test and word recognition of CERAD and Clock Drawing Test were applied to subjects, and to evaluated depression symptoms the GDS was used. Results: This study demonstrated significant diminish in the levels of IL-1β (13.735 vs 22.932 pg/mL; p <0.001) and TNF-α (1.913 vs 2.627 pg/mL; p: 0.002), but not IL-6 (1.913 vs 2.627 pg/mL; p: 0.002), between cases and controls. Individuals with IL-1β < 17 pg/mL were at a 7.2 (CI: 1.5-36; p: 0.016) increased odds of aMCI. Furthermore, there was a positive correlation between IL-1β and the CERAD word list score (rs: 0.299; p: 0.046). The linear regression analysis showed that IL-1β levels can explain 13.7% (β: 24.545; p: 0.012) of the variance on this CERAD subscore, suggesting a direct linear dependence. Conclusion: Neuroinflamation mediated by IL-1β and TNF-α may play an important role in preventing aMCI.
383

Avaliacão da atividade anti-inflamatória do composto LQFM 147, um candidato a protótipo de farmaco / Anti-inflammatory activity evaluation of compound LQFM 147, a candidate a rototype of drug

Vasconcelos, Patricia Antônia 10 September 2016 (has links)
Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2016-09-27T21:13:17Z No. of bitstreams: 2 Dissertação - Patricia Antônia Vasconcelos - 2016.pdf: 2072536 bytes, checksum: 9bdd8a9eab646f3aefc3f2e50a4429e6 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-28T12:21:06Z (GMT) No. of bitstreams: 2 Dissertação - Patricia Antônia Vasconcelos - 2016.pdf: 2072536 bytes, checksum: 9bdd8a9eab646f3aefc3f2e50a4429e6 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-28T12:21:06Z (GMT). No. of bitstreams: 2 Dissertação - Patricia Antônia Vasconcelos - 2016.pdf: 2072536 bytes, checksum: 9bdd8a9eab646f3aefc3f2e50a4429e6 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-09-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Inflammation is a body protection process in response to tissue damage in order to eliminate the offending agent and promote tissue repair. It is characterized by the appearance of the classic signs such as pain, heat, redness and edema, which may occur due to loss as a result of poor resolution of the inflammatory process. The use of antiinflammatory drugs to control inflammation is widely used, but have many side effects, making necessary the search for new drugs with fewer side effects and more effective. The objective of this study was to evaluate the anti-inflammatory activity and / or antinociceptive the LQFM 147 compound using acute tests of nociception and inflammation, to characterize the mechanisms involved in such effects. For this study, male mice were used, weighing between 30 and 35g. Treatment with LQFM 147 at doses of 25, 50 and 100 mg / kg V.O. reduced the number of writhes in a dose-dependent in 16.79; 32.97 and 46.04%, respectively. In the formalin test, treatment with LQFM 147 at a dose of 50 mg / kg V.O. It reduced the time of reactivity to pain testing only the inflammatory phase 43.38%. The anti-inflammatory activity was confirmed, since the treatment with LQFM 147 at a dose of 50 mg / kg V.O. reduced formation of paw edema induced by carrageenan at all hours of the test, reduced migration of polymorphonuclear leukocytes 40.82% in pleurisy test. Treatment with LQFM 147 was able to reduce the activity of myeloperoxidase in 31.54% and TNF-α levels of 65.51%. To obtain the results the group treated with LQFM 147 was compared to the control group treated with vehicle 10 ml / kg v.o .. The data obtained demonstrate that LQFM 147 has anti-inflammatory and antinociceptive activity involving the reduction of migration of polymorphonuclear leukocytes and reduction in TNF-α levels. / Resumo: A inflamação é um processo de defesa do organismo em resposta a lesões teciduais com o objetivo de eliminar o agente agressor e promover o reparo tecidual. É caracterizada pelo aparecimento dos sinais clássicos como dor, calor, rubor e edema, podendo ocorrer a perda da função em consequência da má resolução do processo inflamatório. O uso de fármacos anti-inflamatórios para o controle da inflamação é bastante utilizado, porém possuem muitos efeitos adversos, fazendo necessária à busca por novos fármacos com menos efeitos adversos e mais eficazes. O objetivo deste trabalho foi avaliar a atividade anti-inflamatória e/ou antinociceptiva do composto LQFM 147 utilizando testes agudos de nocicepção e inflamação, visando caracterizar os mecanismos de ação envolvidos em tais efeitos. Para este estudo, foram utilizados camundongos machos, pesando entre 30 e 35 g. O tratamento com LQFM 147 nas doses de 25, 50 e 100 mg/Kg v.o. reduziram o número de contorções abdominais de maneira dose dependente em 16,79; 32,97 e 46,04%, respectivamente. No teste da formalina, o tratamento com LQFM 147 na dose de 50 mg/Kg v.o. reduziu o tempo de reatividade à dor somente na fase inflamatória do teste em 43,38%. A atividade antiinflamatória foi confirmada, uma vez que o tratamento com LQFM 147 na dose de 50 mg/Kg v.o. reduziu a formação do edema de pata induzido por carragenina em todas as horas deste teste, reduziu a migração de leucócitos polimorfonucleares em 40,82% no teste de pleurisia. O tratamento com LQFM 147 foi capaz de reduzir a atividade da enzima mieloperoxidase em 31,54% e os níveis de TNF-α em 65,51%. Para obtenção dos resultados o grupo tratado com LQFM 147 foi comparado com o grupo controle tratado com Veículo 10 mL/kg v.o.. Os dados obtidos demonstram que LQFM 147 possui atividade anti-inflamatória e antinociceptiva envolvendo a redução da migração de leucócitos polimorfonucleares e redução dos níveis de TNF-α.
384

Perfil de citocinas pró- e anti-inflamatória e da proteína c-reativa no tratamento do tumor venéreo transmissível canino / Pro- and anti-inflammatory cytokines and c-reactive protein profiles during the treatment of canine transmissible venereal tumor

Stumpf, Ana Rita Lancini 28 February 2014 (has links)
The canine transmissible venereal tumor (CTVT) is unique in various aspects, and the principal is that the tumoral cells are not originated from the hos t. Recent findings showed that the CTVT is a transplantable tumor that first appeared in a dog ancestor approximately 10000 years ago. The tumoral cells propagate mainly through coitus, develop a s a graft, and have the capability of installing themselves by mechanisms of escape from the host's immunologic response. This specific response involves cellular and humoral immunity and varies according to some factors not yet very elucidated. Beyond the well-known role of fi ghting the tumor cells, the inflammatory response also plays an involuntary and paradoxical role, w hich results in the promotion of tumor growth by releasing vasculogenic, antiapoptotic, and cellular growth- promoting substances. The fact that tumors can benefit from the inf lammatory response makes the investigation of the mechanisms involved important for the development of new therapies focused on the modulation of the inflammatory response to control the tumor development. The aim of this work is to better understand the mechanisms behind tumora l growth by the measurement of the levels of pro-inflammatory (IL-1, IL-6, TNF- α and INF- γ ) and anti- inflammatory (IL-10) cytokines and the C-reactive protein (CRP) ove r the treatment of dogs naturally infected with CTVT. The quantification of the cytokines and CRP was performed in the animals' serum from samples obtained at the moments of the diagnosis and pre-therapy, immediately before chemotherapy, and after the confirmation of the cure of each animal. According to therapy response, two groups were identified, R, were t he tumor was resistant to therapy and NR, which was susceptible. A cure probability was define d in relation to time of treatment and tumor response to vincristin. In group R all parameter s varied significantly: The expression of pro-inflammatory cytokines and CRP were higher, and of I L-10, lower, comparing to group NR. For pro-inflammatory cytokines, this difference was ma intained until cure. Statistical analysis was able to detect correlations betwee n all variables, demonstrating the participation of cytokines during tumor evolution. The role of inflammati on has been postulated and, although the mechanisms remain unclear, a correlation of chronic i nflammation and cancer susceptibility has been demonstrated. Because CTVT is a tumor of foreign cells, it is a suitable model to investigate the mechanisms involved in tumor maintenance and deve loping, as well as the associated immune response. / O tumor venéreo transmissível canino (TVTc) é um tumor único em vários aspectos, sendo o principal, o fato de as células tumorais não serem originárias do animal acometido. Resultados de pesquisas recentes demonstraram que o TVTc é um tumor transplantável que surgiu em ancestrais do cão doméstico há aproximadamente 10000 anos. As células, que se propagam principalmente pelo coito, se desenvolvem como um enxerto e apresentam a capacidade de se implantar através de mecanismos de escape à resposta imunológica do hospedeiro. Essa resposta envolve a imunidade celular e humoral e varia de acordo com fatores não totalmente elucidados. Além do conhecido papel na resposta imune com o objetivo de combater tumores, a resposta inflamatória desempenha um papel involuntário e paradoxal que resulta na promoção do crescimento tumoral pela liberação de substâncias vasculogênicas, antiapoptóticas e promotoras de crescimento celular. O fato de que os tumores possam se beneficiar da resposta inflamatória torna necessárias pesquisas visando o desenvolvimento de terapias direcionadas à modulação da resposta inflamatória para o controle do desenvolvimento tumoral. Dessa forma, o objetivo deste estudo foi compreender melhor os mecanismos envolvidos no desenvolvimento do tumor através da mensuração dos níveis das citocinas pró-inflamatórias (IL- 1, IL-6, TNF-α e INF-γ) e da anti-inflamatória (IL-10) e de uma proteína de fase aguda da inflamação, a Proteína C-reativa (PCR) durante o tratamento de cães naturalmente infectados pelo TVTc. A quantificação das citocinas e da PCR foi realizada no soro dos animais a partir de amostras obtidas no diagnóstico e pré-terapia, imediatamente antes de cada nova aplicação 9 quimioterápica e no momento em que o animal era considerado curado. A partir da resposta à quimioterapia foram caracterizados grupos de animais de acordo com os tumores resistentes (R) e não-resistentes (NR). Foi estabelecida a probabilidade de cura em relação ao tempo de terapia, de acordo com o tipo de tumor. No grupo R, foi observada variação significativa em todos os parâmetros, sendo a expressão das citocinas pró-inflamatórias e da PCR, mais elevadas e a expressão da IL-10 inferior em relação à expressão observada em amostras dos animais do grupo NR. No caso das citocinas pró-inflamatórias e da PCR, essa diferença se manteve até a cura dos animais, diferindo da IL-10, cujas concentrações foram similares nos dois grupos ao final do tratamento. A análise estatística realizada detectou a presença de correlações entre as variáveis, demonstrando a participação das citocinas durante o processo de evolução tumoral. O papel da inflamação no desenvolvimento do câncer foi postulado, apesar de os mecanismos moleculares não terem sido elucidados, sabe-se que a inflamação crônica eleva a probabilidade do desenvolvimento de tumores. Pelo fato de o TVTc ser um tumor de células estranhas ao organismo, seu estudo é importante para verificar os mecanismos relacionados com a manutenção e desenvolvimento dos tumores, bem como da resposta imune associada.
385

Design And Characterization Of Superamolecular Gels And Organic/Inorganic Composite Materials

Das, Rajat Kumar 02 1900 (has links) (PDF)
Chapter 1. A Brief Overview of Low Molecular Mass Gels and their Applications This chapter deals with molecular gels derived from the self-assembly of small organic molecules (typical molecular weight < 2000 daltons), endowed with appropriate functions to promote anisotropic growth of supramolecular aggregates, by means of various non-covalent interactions like van der Waals, π-πstacking, H-bonding etc., leading to a self-assembled fibrillar network (SAFIN). Several representative examples from the literature (Chart 1) are discussed to demonstrate the structural diversity of the gelator molecules which form self-assembled organogels or hydrogels. Chart 1 Besides emphasizing on the diverse molecular structures of the gelators, applications of gel phase materials as functional nanostructures are also discussed (Scheme 1). Some of the aspects that have been elaborated in this context include the use of gels as reaction media, as sensors, in light harvesting, as biomaterials and in optoelectronic applications. Scheme 1 Chapter 2. Supramolecular Chirality in Organogels: Spectroscopic, Morphological and Rheological Investigations of Gels/Xerogels derived from Alkyl Pyrenyl Urethanes This chapter addresses the formation of chiral supramolecular structures in the organogels derived from chiral 1R (or 2R), and its mixture with its enantiomer (1S) and a series of achiral analogues (3-9) by extensive circular dichroism (CD) spectroscopic measurements (Chart 2). Morphological studies by atomic force microscopy (AFM) and scanning electron microscopy (SEM) were complemented by the measurements of their bulk properties by thermal stability and rheological studies. Specific molecular recognition events (1/3 vs 2/3) and solvent effects (isooctane vs dodecane) were found to be critical in the formation of the chiral aggregates. Computational studies were carried out to understand the interactions responsible for the formation of chiral superstructures. Chapter 3. Self-assembled Composite Organogels based on a Thermo-reversible Photoactive n-Acene Fibrillar Scaffold and Organic Ligand stabilized ZnO Nanoparticles Organic/inorganic composite organogels were obtained in n-BuOH by the self-assembly of 2,3-di-n-decyloxyanthracene (DDOA, Chart 3) in this solvent in the presence of ZnO nanoparticles (NPs) capped with different organic ligands (Chart 4). When ligands (oleic acid or 2,3-substituted anthracenic acid/oleic acid mixed shell) having structural similarity with the gelator molecule were used to cap the NPs, a homogeneous dispersion of the NPs in the gel matrix was obtained, as confirmed by microscopy (TEM and confocal fluorescence microscopy) experiments. The efficient integration of these NPs into the gel fibers resulted in a significant quenching (20-25%) of DDOA emission, even with extremely small loading of these NPs (~ 10-4mol% compared to DDOA) into the gel fibers. The mechanical properties (rheology were unaffected relative to the pristine DDOA organogel. However, the presence of the NPs lowered the critical gelation concentration and accelerated the gelation kinetics. Attempts to disperse these NPs (the ones without fluoro capping) on the aerogel fibers of DDOA by dissolving both DDOA and the NPs in supercritical (sc) CO2 were not successful (Fig. 1), since the NPs could not be dissolved in scCO2. Figure 1. (a) TEM images of DDOA aerogels obtained from scCO2, containing A23-NPs, scale bar 200 nm; (b) SEM image of DDOA aerogel obtained in the presence of OL-NPs, scale bar 10 µm. Chapter 4. Donor-Acdeptor Interaction Promoted Gelation Of Organic Fluids by Anthracene Carboxamides/2,4,7-Trinitrofluorenone Tris Carboxamides of anthracene were found to form charge-transfer driven organogels in a range of aliphatic alcohols in the presence of an equivalent of (electron-deficient) 2,4,7-trinitrofluorenone (TNF) (Chart 5). Intense color developed in the gel state during the sol to gel phase transition process (Fig 2) Besides, none of these carboxamides were able to form gel in the absence of TNF, suggesting the importance of charge-transfer interaction in the gel formation. Importantly, most of these gels formed only through rapid cooling of the hot solution, otherwise, leading to the precipitation of the CT complex from the solvent. This result indicated that the kinetics is very important for the formation of these gels. Optimum stoichiometry of the donor and acceptor was found to be 1:1. At this molar ratio of the donor and the acceptor, the gels not only showed the highest thermal stability (thermal gel melting experiments), they also displayed the highest values of the mechanical strength and the yield stress (rheology experiments). All the gels showed extensive quenching of the emission of the monomeric anthracenic donor. For the gels derived from the 2-substituted donor, a low energy emission at high wavelength indicated the formation of an emissive CT exciplex. X-ray powder diffraction studies of these xerogels revealed the presence of layered, fibrillar structures in the xerogel phase. (For structural formula pl see the abstract file)
386

Etude phytochimique et activité biologique du produit Gencix® extrait des feuilles de papayer / Phytochemical study and biological activity of the Gencix® product extracted from papaya leaves

Dejoie, Stéphane 08 December 2017 (has links)
Utilisé dans l’entretien et le soin des gencives et des dents, le produit Gencix® (SAS Esprit d’éthique) a montré, d’après les observations cliniques des dentistes, une action anti-inflammatoire et nettoyante des dents. Ce dentifrice incorpore un extrait aqueux de feuilles de papayer. Afin d’en comprendre le mécanisme d’action en termes de métabolites actifs, un fractionnement bioguidé et une étude déréplicative associant LCUV- MSn et RMN du 13C ont été menés. L’activité relevée en clinique ne semble pas liée à un effet antibiofilm. Une activité anti-inflammatoire (anti-TNF-alpha) serait liée aux flavonoïdes plus ou moins glycosylés présents dans l’extraits. Nous avons en effet pu identifier quelques-uns des actifs comme la quercétine et le kaempferol, déjà décrits comme inhibiteurs de la libération du TNF- alpha. D'autres flavonols libres ou conjugués tels que la rutine, identifiés dans les fractions actives, peuvent également contribuer à l'activité anti-inflammatoire globale. Plus notablement, au cours de ce travail, des esters des acide malique et hydroxycinnamique ont pour la première fois été associés à une activité anticalcaire, en particulier l’acide caféoylmalique. Ce dernier agit sans doute en synergie avec d’autres composés analogues. Les différents groupements acides carboxyliques et hydroxyles présents dans ces dérivés agissent vraisemblablement en complexant les ions Ca2+. Au-delà de ces résultats, ces anticalcaires nouvellement identifiés apparaissent comme des actifs « verts » (non toxiques, n’entraînant pas de bioaccumulation et biodégradables), respectueux de l'environnement. Cette activité anticalcaire remarquable a fait l’objet d’un dépôt de brevet. / Gencix® (SAS Esprit d’Ethique) is used for the maintenance and care of gums and teeth. Clinical observations reported from dentists showed that this product-integrating anaqueous Carica papaya leaf extract- showed teeth cleaning and anti-inflammatory properties. In order to understand the mechanism of action and the role of the metabolites of the plant extract, a bioguided fractionation and a dereplicative study associating LC-UV-MSn and 13C NMR were conducted. Clinical activity does not appear to be related to an antibiofilm effect. The anti-inflammatory (anti-TNF-alpha) activity is most probably associated with glycosylated flavonoids. We have been able to identify some of the active ingredients such as quercetin and kaempferol which are already known to inhibit the release of TNF-α. Other free or conjugated flavonols such as rutin, identified in the active fractions, may also contribute to the overall anti-inflammatory activity. Most notably, esters of malic and hydroxycinnamic acids were described for the first time as scaling inhibitors, particularly caffeoyl malate. This compounds probably acts in synergy with other analog compounds. The various hydroxyl and carboxylic groups present in these compounds are probably responsible for this activity by complexing Ca2+ ions. Beyond these results, these metabolites, which are newly identified as anti-scalant, appear as "green" (i. e. non-toxic, non-bioaccumulative and biodegradable) as well as environmentally friendly. Therefore, this outstanding scaling inhibition property was subjected to patent application.
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Identification of Putative Receptors for the Novel Adipokine CTRP3 Using Ligand-Receptor Capture Technology

Li, Ying, Ozment, Tammy, Wright, Gary L., Peterson, Jonathan M. 11 October 2016 (has links)
C1q TNF Related Protein 3 (CTRP3) is a member of a family of secreted proteins that exert a multitude of biological effects. Our initial work identified CTRP3’s promise as an effective treatment for Nonalcoholic fatty liver disease (NAFLD). Specifically, we demonstrated that mice fed a high fat diet failed to develop NAFLD when treated with CTRP3. The purpose of this current project is to identify putative receptors which mediate the hepatic actions of CTRP3. Methods We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment with CTRP3-FLAG protein as ligand and insulin as a control ligand was performed on the H4IIE rat hepatoma cell line. Results Initial analysis demonstrated efficient coupling of TriCEPS to CTRP3. Further, flow cytometry analysis (FACS) demonstrated successful oxidation and crosslinking of CTRP3-TriCEPS and Insulin-TriCEPS complexes to cell surface glycans. Demonstrating the utility of TriCEPS under these conditions, the insulin receptor was identified in the control dataset. In the CTRP3 treated cells a total enrichment of 261 peptides was observed. From these experiments 5 putative receptors for CTRP3 were identified with two reaching statistically significance: Lysosomal-associated membrane protein 1 (LAMP-1) and Lysosome membrane protein 2 (LIMP II). Follow-up Co-immunoprecipitation analysis confirmed the association between LAMP1 and CTRP3 and further testing using a polyclonal antibody to block potential binding sites of LAMP1 prevented CTRP3 binding to the cells Conclusion The LRC-TriCEPS methodology was successful in identifying potential novel receptors for CTRP3. Relevance The identification of the receptors for CTRP3 are important prerequisites for the development of small molecule drug candidates, of which none currently exist, for the treatment NAFLD.
388

Role of Covalent Modification of Hyaluronan with Inter-Alpha Inhibitor Heavy Chains During Acute Lung Injury

Ni, Kevin Chen 04 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / The extracellular matrix (ECM) provides a structural and signaling platform for cells that comprise various organs, playing a critical role in tissue maintenance, injury, and repair. Hyaluronan (also known as hyaluronic acid, HA) is a ubiquitous ECM polysaccharide consisting of a repeating disaccharide backbone that can be covalently modified by the heavy chains (HC) of the serum protein inter-alpha-inhibitor (IαI) during inflammation. Known as the only covalent modification of HA, the HC linking of HA is exclusively mediated by the inflammation-induced secreted enzyme TNFα-stimulated gene-6 (TSG-6). Mice deficient for HC-HA formation, due to the lack of either TSG-6 or IαI, display reduced survival during systemic lipopolysaccharide (LPS)-induced endotoxic shock and its associated acute lung injury. We therefore hypothesized that HC-HA should play an important protective role against acute lung injury induced by intratracheal LPS or Pseudomonas aeruginosa (PA) gram-negative bacteria. We also identified that lung instillation of LPS or PA caused rapid induction of lung parenchymal HC-HA that was largely cleared during resolution of injury, indicative of a high rate of HA turnover and remodeling during reversible lung injury. However, using TSG-6 knockout mice, we determined that HC-HA exerted minimal protective effects against intratracheal LPS or PA-induced acute lung injury. To better address the differential roles of HC-HA during systemic versus localized intratracheal exposure to LPS, we characterized and compared the induction of HC-HA in plasma and lung in these two models. While lung parenchymal HC-HA formed in both injury models, intravascular HC-HA and TSG-6 were exclusively induced during systemic LPS exposure and were associated with improved outcomes, including decreased number of circulating neutrophils and plasma TNFα levels. Our results suggest that LPS induces HC-HA formation in various tissues depending on the route of exposure and that the specific intravascular induction of HCHA during systemic LPS exposure may have a protective role during endotoxic shock.
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Characterization of the antibodies and antibody technologies to improve the pharmaceutical activity / 薬学的活性を改善するための抗体および抗体技術に関する研究

Shinmi, Daisuke 23 January 2018 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(工学) / 乙第13145号 / 論工博第4163号 / 新制||工||1687(附属図書館) / (主査)教授 森 泰生, 教授 浜地 格, 教授 梅田 眞郷 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM
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Kinetics of Microvesicle Particle Release in Keratinocytes

Thapa, Pariksha 27 August 2019 (has links)
No description available.

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