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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.
101

Migrän: En osynlig sjukdom : En litteraturstudie om icke-farmakologiska metoder vid migränanfall hos vuxna / Migraine: an invisible disorder : A literature study on non-pharmacological methods in adult patients with migraine

Andersson, Jonna, Gaviola Poblete, Marianne, Volioti, Christina January 2014 (has links)
Migrän är en återkommande, anfallsvis huvudvärk som räknas till en av de 20 mest handikappande sjukdomarna i världen. Det är sjuksköterskans ansvar att främja hälsan hos patienter med migrän genom att upplysa om sjukdomen och informera om vilka icke-farmakologiska metoder som kan verka mot migrän. Syftet med studien var att beskriva icke-farmakologiska metoder vid migränanfall hos vuxna. Litteraturstudiens resultat baserades på 13 vetenskapliga artiklar som genererade tre olika teman: akupunktur, kunskap kring utlösande faktorer samt livsstilsförändringar. Resultatet visade att akupunktur, kunskap och utbildning kring utlösande faktorer samt livsstilsförändringar är bra behandlingsalternativ i det hälsofrämjande arbetet vid migrän, då metoderna visade på signifikant minskning av migränanfall. För att bevisa om metoderna är tillförlitliga behövs ytterligare forskning angående icke-farmakologiska metoder vid migrän. Utformning av riktlinjer gällande migrän och adekvata behandlingsmetoder ute i vårdverksamheten vore betydelsefullt. Utökad utbildning om migrän i sjuksköterskeutbildningarna är av stor vikt. / Migraine is a recurrent headache that occurs in periods of sudden attacks and is regarded as one of the 20 most disabling disorders in the world. It is the responsibility of the nurse to promote the health of patients with migraine by educating about migraine and by providing vital information about non-pharmacological methods that has beneficial effects on migraine. The aim of this literature study was to describe non-pharmacological methods on adult migraine patients. The result of this literature study was based on 13 scientific articles that generated three themes: acupuncture, knowledge about trigger factors and lifestyle changes. The result showed that acupuncture, knowledge about migraine triggers and lifestyle changes are favourable alternative treatments in migraine health promotion as they demonstrated significant reduction of migraine attacks. To attest its validity further research regarding the use of non-pharmacological methods on migraine is necessary. Specific guidelines regarding migraine and adequate available treatment methods in healthcare settings would be of great importance. We encourage additional education on migraine and nonpharmacological, preventive methods to be integrated in nursing schools.
102

Development and Validation of a Novel Quantitative Assay for Cell surface Expression of GPCRs using a Receptor β-lactamase fusion Protein and the Colourometric Substrate Nitrocefin

Lam, Vincent 12 July 2013 (has links)
Trafficking of GPCRs is a dynamic process that is tightly regulated and sometimes defective in human diseases. Therefore it is important to develop new methods to allow simple and quantitative measurement of surface expression of membrane proteins. Here we describe the development and validation of a new assay for quantification of cell surface expression of GPCRs using β-lactamase as a reporter. For this assay we N-terminally fused β-lactamase (βlac) to the β2-adrenergic receptor (β2AR) and GABA b R1 (GBR1). The results obtained by the βlac assay are quantitatively and qualitatively similar to well established ELISA when measuring agonist induced internalization of β2AR. We also show that measurement of GBR1 surface expression with GBR2 co-expression is quantitatively identical between the βlac and ELISA. In conclusion, our results show that our newly developed βlac assay is quantitatively similar while being less expensive, more robust and higher throughput compared to an ELISA.
103

Development and Validation of a Novel Quantitative Assay for Cell surface Expression of GPCRs using a Receptor β-lactamase fusion Protein and the Colourometric Substrate Nitrocefin

Lam, Vincent 12 July 2013 (has links)
Trafficking of GPCRs is a dynamic process that is tightly regulated and sometimes defective in human diseases. Therefore it is important to develop new methods to allow simple and quantitative measurement of surface expression of membrane proteins. Here we describe the development and validation of a new assay for quantification of cell surface expression of GPCRs using β-lactamase as a reporter. For this assay we N-terminally fused β-lactamase (βlac) to the β2-adrenergic receptor (β2AR) and GABA b R1 (GBR1). The results obtained by the βlac assay are quantitatively and qualitatively similar to well established ELISA when measuring agonist induced internalization of β2AR. We also show that measurement of GBR1 surface expression with GBR2 co-expression is quantitatively identical between the βlac and ELISA. In conclusion, our results show that our newly developed βlac assay is quantitatively similar while being less expensive, more robust and higher throughput compared to an ELISA.
104

A biophysical study of intranuclear herpes simplex virus type 1 DNA during lytic infection

Lacasse, Jonathan J 11 1900 (has links)
Herpes Simplex Virus Type 1 (HSV-1) establishes latent infections in neurons in vivo and lytic infections in epithelial cells and fibroblasts. During latent infections, HSV-1 transcription is restricted and the genomes are not replicated. Latent HSV-1 genomes are chromatinized, such that digestion with micrococcal nuclease (MCN) releases DNA fragments with sizes characteristic of nucleosomal DNA. During lytic infections, in contrast, all HSV-1 genes are expressed, the genomes are replicated, and their digestion produces primarily heterogeneously sized fragments. However, as evaluated by ChIP assays, HSV-1 DNA interacts with histones during lytic infections, although in most cases only a small percentage of HSV-1 DNA co-immunoprecipitates with histones (or is cleaved to nucleosome sizes following MCN digestion). Therefore, although current models propose that chromatin regulates HSV-1 transcription, it remains unclear how the association of histones with only a small percentage of HSV-1 DNA can globally regulate viral transcription. Moreover, the physical properties of the complexes containing histones and HSV-1 DNA are unknown. My objective was therefore to evaluate the biophysical properties of the HSV-1 DNA-containing complexes during lytic infection. Differing from pervious studies, however, I used classical chromatin purification techniques. I show that most HSV-1 DNA is in unstable nucleoprotein complexes and, consequently, more accessible to MCN than DNA in cellular chromatin. This HSV-1 DNA is protected from MCN redigestion only after crosslinking, similar to unstable cellular nucleosomes. HSV-1 DNA is in such complexes throughout lytic infection. Using unrelated small-molecule inhibitors, I further show that inhibition of HSV-1 transcription is associated with a decrease in MCN accessibility of HSV-1 DNA. Roscovitine, a cyclin-dependent kinase inhibitor, prevents activation but not elongation of IE, E, and L HSV-1 transcription. Consistent with a functional association between accessibility and transcription, roscovitine only decreases the accessibility of DNA templates of which it also inhibits transcription, independent of specific promoter sequences. In summary, I show that most HSV-1 DNA is in unstable nucleosome-like complexes during lytic infection and that accessibility to HSV-1 DNA likely plays a key role in regulating HSV-1 transcription.
105

Eventos adversos em projetos de pesquisa farmacológica : incidência dos relatos de eventos adversos relacionados aos riscos gastrintestinais mais citados nos protocolos de pesquisa

Pedroso, Ana Paula da Silva January 2012 (has links)
Introdução: A pesquisa na área farmacológica envolvendo seres humanos é fundamental para a geração de novos conhecimentos, com a finalidade de trazer benefícios na assistência, porém apresenta riscos associados. Conforme o Manual para Boas Práticas em Pesquisa Clínica (GCP), Evento Adverso (EA) é “qualquer ocorrência médica inconveniente, sofrida pelo participante da pesquisa ou sujeito em investigação clínica com fármacos e que não possui, necessariamente, uma relação causal com este tratamento”. Objetivo: Verificar a incidência de Eventos Adversos (EAs) relacionados aos riscos gastroenterológicos mais citados em protocolos de pesquisa farmacológica. Métodos: Trata-se de um estudo de casos incidentes (coorte não-controlada). O fator em estudo foi o conjunto dos eventos adversos gastrintestinais (EA-GI) relatados. Foram avaliados os relatos de eventos adversos comunicados ao Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre no período de janeiro a dezembro de 2010. Nos últimos doze meses foram monitorados 110 diferentes projetos de pesquisa farmacológica com um acumulado de 8179 relatos de eventos adversos avaliados. Resultados: Da amostra de 26 diferentes projetos envolvidos ao longo de 2010 (jan-dez), foram relatados 63 ocorrências de EA-GI. Os EA-GI mais frequentes foram náusea/vômitos com 21 (33,3%) das ocorrências; outras dores abdominais e as não especificadasl com 12 (19%); alteração do hábito intestinal com dez (15,9%) das ocorrências; elevação das enzimas hepáticas com nove (14,3%) e os demais EA-GI com 17, 5%. Estes EA-GI comparativamente aos riscos descritos não estavam adequadamente descritos nos documentos dos protocolos de pesquisa. Conclusão: As presentes conclusões evidenciam a necessidade de uma avaliação criteriosa dos Comitês de Ética em Pesquisa com relação à documentação dos protocolos de pesquisa a serem avaliados e dos relatos de eventos adversos a serem monitorados. O conjunto destas avaliações - prévia e continuada - devem sempre buscar a proteção adequada dos participantes dos projetos de pesquisa. / Background: Human pharmacological research is essential for the generation of new knowledge in order to generate benefits in health care, but risks are associated. According to the Handbook for Good Clinical Practice (GCP), Adverse Event (AE) is "any untoward medical occurrence inconveniences suffered by the participant or subject of research in clinical research with drugs and do not necessarily have a causal relationship with this treatment ". Objective: To determine the incidence of adverse events (AEs) related to the most cited gastroenterological risks in pharmacological research protocols. Methods: An incident cases study (non-controlled cohort) was performed. The factor under study was the set of GI adverse events (AE-GI) reported. We assessed reports of adverse events reported to the Hospital de Clinicas de Porto Alegre Research Ethics Committee from January to December 2010. In the last twelve months have been monitored more than 110 different pharmacological research projects with a cumulative 8,179 adverse event reports evaluated (3). Results: The sample involved 26 different projects in 2010 (Jan-Dec), 63 occurrences were reported as EA-GI. The EA-GI were more frequent nausea / vomiting 21 (33.3%) of cases, abdominal pain with 12 (19%), diarrhea with ten (15.9%) of cases, elevated liver enzymes with nine (14 3%) and other GI with EA-17, 5%. The reports occurred in other associated centers totaling 87.3% and 12.7% at HCPA. Conclusion: These findings highlight the need for a careful evaluation of the Research Ethics Committee specially when documents of research protocols were evaluated and when adverse events reports were monitored. All these evaluations - prior and ongoing - should always seek appropriate protection of participants in research projects.
106

Phytochemical and pharmacological studies of two Vietnamese traditional plants : Medinilla septentrionalis (W.W.SM.) H.L. Li and Dacrycarpus imbricatus (Blume) de Laub / Etude phytochimique et pharmacologique de deux plantes issues de la médecine traditionnelle vietnamienne : Medinilla septentrionalis (W.W.SM) H.L. Li et Dacrycarpus imbricatus (Blume) de Laub

Nguyen, Xuân Minh Ài 16 November 2017 (has links)
La présente étude a été menée dans le but de documenter les connaissances concernant l'utilisation traditionnelle de plantes médicinales par la minorité ethnique K'Ho qui réside au parc national BiDoup-Núi Bà, province de Lâm Đồng, au Vietnam. Une enquête ethnobotanique a été réalisée de 2013 à 2015 sur 139 habitants de trois villages, dont 12 informateurs référents compétents en plantes médicinales et 127 informateurs non spécialistes. À partir de 133 plantes médicinales obtenues à l’issue de l’enquête, deux plantes ont été choisies pour des travaux de recherche. Medinilla septentrionalis (Melastomataceae) est utilisé pour la toux et la diarrhée dans l’ethnie K'Ho. Le criblage phytochimique préliminaire a été réalisé sur 16 extraits bruts obtenus à partir des pousses, tiges, feuilles et des parties aériennes avec différents solvants. Leurs bioactivités ont également été évaluées. L’alpha-amyrine a été isolée à partir de l’extrait dichlorométhane de la tige. Quatre composés: vescalagine, castalagine, méthylvescalagine et l'acide protocatéchique, ont été identifiés à partir de l'extrait méthanolique des tiges.Dacrycarpus imbricatus (Podocarpaceae) est utilisé traditionnelle pour traiter la diarrhée, la toux et les démangeaisons. Seize extraits bruts provenant du bois, de l'écorce, des feuilles et des parties aériennes avec différents solvants ont été soumis à des études phytochimiques et pharmacologiques préliminaires. L’extrait aqueux du bois a été sélectionné pour un fractionnement bioguidé, permettant l’isolement du 3-O--D-Glucopyranosyl--sitosterol. Deux alcaloïdes: la sanjoinine A et à la scutianine C, ont été isolés à partir des parties aériennes par RNM. / The present study was conducted to document the traditional knowledge of medicinal plants used by K’Ho people who reside at BiDoup-Núi Bà National Park, Lâm Đồng Province, Vietnam. An ethnobotanical survey from 2013 to 2015 was carried out with 139 local people from three K’Ho villages, including 12 key informants who are knowledgeable in medicinal plants and 127 non-specialist informants. From 133 medicinal plants obtained through the survey, two potential plants were chosen for further studies. Medinilla septentrionalis (Melastomataceae) is traditionally used for cough and diarrhea. The preliminary phytochemical screening was carried out on 16 crude extracts obtained from sprout, stem, leaves and aerial parts of the plant with different solvents. At the same time, their bioactivities were also evaluated. Dichloromethane extract of stem and methanol extract of sprout exhibiting anti-inflammatory activity were chosen for bioguided fractionation. Alpha-amyrin was isolated from dichloromethane extract of stem. Four compounds, including vescalagin, castalagin, methylvescalagin and protocatechoic acid, were purified from methanol extract of sprout.Dacrycarpus imbricatus (Podocarpaceae) is used for the treatment of diarrhea, cough and itching by local people. Sixteen crude extracts obtained from wood, bark, leaves and aerial parts with different solvents were subjected to preliminary phytochemical and pharmacological studies. Aqueous extract of wood was chosen for the next bioguided fractionation, from which 3-O--D-Glucopyranosyl--sitosterol was isolated. Moreover, two alkaloids obtained from the aerial parts were identified as sanjoinine A and scutianine C.
107

Conception et synthèse d'iminoglycolipides comme inhibiteurs d'enzymes lysosomales à effet chaperon pharmacologique / Conception and synthesis of iminoglycolipids as inhibitors of lysosomal enzymes acting as pharmacological chaperones

OulaÏdi, Farah 28 January 2011 (has links)
La thérapie chaperon représente une approche thérapeutique stratégique et innovante, en particulier dans le traitement des maladies lysosomales. Ces maladies génétiques rares ont une gravité variable, qui peut aller de la létalité avant la naissance jusqu’à la nécessité d‟une prise en charge permanente ; elles apparaissent à tous les stades de la vie. Des mimes du substrat appelé iminosucres, vont agir en allant au coeur du site actif de l’enzyme, stabiliser l’enzyme mutée qui est instable mais non inactive. Paradoxalement, la plupart des chaperons pharmacologiques sont des inhibiteurs de l’enzyme visée mais leur administration à faible concentration leur permet de réaliser leur mission de sauvetage de l’enzyme mutée. Dans cette optique, des recherches effectuées au sein de notre laboratoire ont fait état de la synthèse d’iminosucres, tels que les α-1-C-alkyl iminoxylitols qui sont de très bons inhibiteurs de la β-glucocérébrosidase, l’enzyme défaillante dans la maladie de Gaucher, mais aussi qui doublent l’activité enzymatique résiduelle. Une nouvelle voie de synthèse plus efficace a été réalisée afin d’obtenir plus efficacement ce type d’iminosucres et d’autres dérivés. Ces travaux ont également été l’occasion de développer des iminoxylitols structurellement simplifiés qui agissent comme chaperons pharmacologiques toujours pour le traitement de la maladie de Gaucher. Une partie de ces travaux a aussi été consacrée à la recherche d‟inhibiteurs de la β-galactocérébrosidase, l’enzyme impliquée dans la maladie de Krabbé, et qui pourront agir comme chaperons pharmacologiques. Différentes évaluations pharmacologiques ont été réalisées, notamment des tests d’inhibition et la détermination des effets chaperons. / Chaperone Mediated Therapy represents an innovative and strategic approach to treat lysosomal storage disorders which a class of rare genetic diseases. Competitive inhibitors for some of these lysosomal enzymes can, at sub inhibitory concentrations, act as chaperones and rescue the mutant proteins. In fact, enzymes carrying some mutations are still catalytically active. α-1-C-alkyl iminoxylitols represent a class of iminosugars which mimic the “gluco” configuration of the substrate and give powerful inhibitors of β-glucocerebrosidase, the enzyme involved in Gaucher disease. Moreover, this class of iminosugars, synthesized by our group, act as pharmacological chaperones and are able to double the residual activity of the N370S mutant. In order to synthesize more efficiently these iminosugars, the synthetic strategy was improved and optimized. Moreover, we focused our investigations on structural variations on our lead compound (α-1-C9 iminoxylitol) and draw important conclusions on structure-activity relationship. Then, we extended our expertise on iminosugars as pharmacological chaperones to another lysosomal glycosidase. In paricular, we targeted β-galactocerebrosidase, the enzyme responsible for Krabbe disease, and synthesized a series of iminosugars which mimic the “galacto” configuration. Biological assays were performed on our compounds to determine their activity as inhibitors and for some of them, their chaperone effects.
108

Eventos adversos em projetos de pesquisa farmacológica : incidência dos relatos de eventos adversos relacionados aos riscos gastrintestinais mais citados nos protocolos de pesquisa

Pedroso, Ana Paula da Silva January 2012 (has links)
Introdução: A pesquisa na área farmacológica envolvendo seres humanos é fundamental para a geração de novos conhecimentos, com a finalidade de trazer benefícios na assistência, porém apresenta riscos associados. Conforme o Manual para Boas Práticas em Pesquisa Clínica (GCP), Evento Adverso (EA) é “qualquer ocorrência médica inconveniente, sofrida pelo participante da pesquisa ou sujeito em investigação clínica com fármacos e que não possui, necessariamente, uma relação causal com este tratamento”. Objetivo: Verificar a incidência de Eventos Adversos (EAs) relacionados aos riscos gastroenterológicos mais citados em protocolos de pesquisa farmacológica. Métodos: Trata-se de um estudo de casos incidentes (coorte não-controlada). O fator em estudo foi o conjunto dos eventos adversos gastrintestinais (EA-GI) relatados. Foram avaliados os relatos de eventos adversos comunicados ao Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre no período de janeiro a dezembro de 2010. Nos últimos doze meses foram monitorados 110 diferentes projetos de pesquisa farmacológica com um acumulado de 8179 relatos de eventos adversos avaliados. Resultados: Da amostra de 26 diferentes projetos envolvidos ao longo de 2010 (jan-dez), foram relatados 63 ocorrências de EA-GI. Os EA-GI mais frequentes foram náusea/vômitos com 21 (33,3%) das ocorrências; outras dores abdominais e as não especificadasl com 12 (19%); alteração do hábito intestinal com dez (15,9%) das ocorrências; elevação das enzimas hepáticas com nove (14,3%) e os demais EA-GI com 17, 5%. Estes EA-GI comparativamente aos riscos descritos não estavam adequadamente descritos nos documentos dos protocolos de pesquisa. Conclusão: As presentes conclusões evidenciam a necessidade de uma avaliação criteriosa dos Comitês de Ética em Pesquisa com relação à documentação dos protocolos de pesquisa a serem avaliados e dos relatos de eventos adversos a serem monitorados. O conjunto destas avaliações - prévia e continuada - devem sempre buscar a proteção adequada dos participantes dos projetos de pesquisa. / Background: Human pharmacological research is essential for the generation of new knowledge in order to generate benefits in health care, but risks are associated. According to the Handbook for Good Clinical Practice (GCP), Adverse Event (AE) is "any untoward medical occurrence inconveniences suffered by the participant or subject of research in clinical research with drugs and do not necessarily have a causal relationship with this treatment ". Objective: To determine the incidence of adverse events (AEs) related to the most cited gastroenterological risks in pharmacological research protocols. Methods: An incident cases study (non-controlled cohort) was performed. The factor under study was the set of GI adverse events (AE-GI) reported. We assessed reports of adverse events reported to the Hospital de Clinicas de Porto Alegre Research Ethics Committee from January to December 2010. In the last twelve months have been monitored more than 110 different pharmacological research projects with a cumulative 8,179 adverse event reports evaluated (3). Results: The sample involved 26 different projects in 2010 (Jan-Dec), 63 occurrences were reported as EA-GI. The EA-GI were more frequent nausea / vomiting 21 (33.3%) of cases, abdominal pain with 12 (19%), diarrhea with ten (15.9%) of cases, elevated liver enzymes with nine (14 3%) and other GI with EA-17, 5%. The reports occurred in other associated centers totaling 87.3% and 12.7% at HCPA. Conclusion: These findings highlight the need for a careful evaluation of the Research Ethics Committee specially when documents of research protocols were evaluated and when adverse events reports were monitored. All these evaluations - prior and ongoing - should always seek appropriate protection of participants in research projects.
109

Participação da isoforma proteína quinase C βII na insuficiência cardíaca / Involvement of protein kinase C βII in heart failure

Julio Cesar Batista Ferreira 11 August 2009 (has links)
A insuficiência cardíaca é uma síndrome clínica de mau prognóstico caracterizada por disfunção cardíaca associada à intolerância aos esforços, retenção de fluído e redução da longevidade. Dentre as serina/treonina quinases associadas às alterações funcionais e estruturais cardíacas observadas na progressão da insuficiência cardíaca, a família das proteínas quinase C (PKC) composta por 12 diferentes isoformas parece modular a contratilidade miocárdica e o remodelamento cardíaco. No presente estudo, caracterizamos o fenótipo cardíaco e o perfil de ativação das diferentes isoformas de PKC na progressão da insuficiência cardíaca de etiologia isquêmica em ratos. Além disso, estudamos o efeito da inibição sustentada da isoforma PKCβII sobre a sobrevida, o remodelamento cardíaco e a função ventricular em modelo de insuficiência cardíaca de etiologia isquêmica. Conseguinte, identificamos possíveis substratos cardíacos da PKCβII envolvidos na progressão da insuficiência cardíaca. Para isso, avaliamos os efeitos agudo e crônico da inibição da PKCβII sobre o transiente de cálcio e a contratilidade de cardiomiócito isolados de ratos adultos com insuficiência cardíaca. Por fim, testamos as inibições específicas das PKCβII e PKCβI na progressão da hipertrofia cardíaca compensada para a insuficiência cardíaca em modelo animal de hipertensão arterial sustentada. Nossos resultados sugerem que a inibição sustentada da PKCβII reverte o quadro de insuficiência cardíaca, melhorando a função ventricular, o remodelamento cardíaco e a sobrevida dos diferentes modelos de insuficiência cardíaca estudados, constituindose em uma estratégia terapêutica celular promissora / Heart failure is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality worldwide. Protein kinase C isozymes emerge as important potential therapeutic targets in chronic cardiovascular disease. However, individual PKC isozymes play different roles in the pathogenesis of cardiac diseases. Here, we characterized the cardiac phenotype as well as the different PKC isozyme activation profile during myocardial-induced heart failure progression in rat. Furthermore, we evaluated the role of selective PKCβ II inhibition on survival, left ventricle remodeling and cardiac function in myocardial-induced heart failure. Moreover, we identified the cardiac PKCβII substrates related to heart failure. Finally, PKCβII and PKCβI specific inhibitors were chronically delivered to hypertensive-induced heart failure rats and the cardiac phenotype was evaluated. Our data suggest that 6-wks of PKCβII inhibition, but not PKCβI, improved animal survival by restoring cardiac function and promoting cardiac anti-remodeling effect in both myocardial infarctioninduced heart failure and hypertensive-induced heart failure rats. The improved cardiac function and anti-remodeling effect of PKCβII inhibition seems to be associated with increased contractility of cardiac myocytes, improved miofilaments/Ca2+ sensitivity and decreased cardiac inflammatory response. Altogether, the results provide evidence for beneficial effects of PKCβII specific intracellular inhibition on cardiac function and remodeling, which may be a promising cellular therapy for heart failure treatment
110

Use of protein monocyte chemoattractant-1 as a biomarker early kidney injury in patients with sickle cell disease / Uso da proteÃna quimiotÃtica de monÃcitos-1 como biomarcador de lesÃo renal precoce em pacientes com anemia falciforme

Talyta Ellen de Jesus dos Santos 17 April 2014 (has links)
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Novos biomarcadores da funÃÃo renal estÃo sendo estudados com o propÃsito de detectar precocemente alteraÃÃes renais em portadores de AF, dentre eles encontra-se a proteÃna quimiotÃtica de monÃcitos 1 (MCP-1), uma quimiocina de monÃcitos e macrÃfagos, produzida por cÃlulas do sistema renal em resposta ao processo de isquemia-reperfusÃo. OBJETIVO: Avaliar o uso de MCP-1 como biomarcador de lesÃo renal precoce em pacientes adultos com anemia falciforme em uso ou nÃo de hidroxiureia (HU). METODOLOGIA: Participaram do estudo 50 pacientes: 30 em uso de (HU)-grupo SSHU e 20 sem HU-grupo SS. Um grupo controle foi composto por 20 indivÃduos com HbAA, sem complicaÃÃes renais. ProteinÃria, albuminÃria, creatinina e urÃia urinÃrias, marcadores do estresse oxidativo como MDA e NOx foram determinados por mÃtodos espectrofotomÃtricos. MCP-1 urinÃrio foi detectado por enzima imunoensaio (ELISA). Os dados clÃnicos e de hemograma, creatinina e ureia sÃricas foram retirados do prontuÃrio mÃdico. Foi coletada a primeira urina do dia. O programa Graph Pad Prism 5.0 foi utilizado para anÃlise estatÃstica. A comparaÃÃo das mÃdias entre os grupos foi realizada atravÃs do teste t de Student e anÃlise de variÃncia (ANOVA). RESULTADOS E DISCUSSÃO: Albumina urinÃria esteve maior nos pacientes em relaÃÃo ao grupo controle (Controle-3.12 Â 4.35; SSHU- 11.85 Â 9.16; SS- 14.13 Â 12.22; p <0.0001). A taxa de filtraÃÃo glomerular estimada apresentou-se significantemente menor no grupo controle (Controle- 95.9 Â 19.92; SSHU- 137.9 Â 40.7 e SS- 140.1 Â 53.9; p= 0.0024). Observaram-se nÃveis elevados de MCP-1 (Controle- 42.12 Â 27.6; grupo SSHU- 166.2 Â 88.37 e grupo SS- 219.7 Â 115.0; p<0.001; p=0.039); MDA (Controle- 2.29 Â 1.13; grupo SSHU-5.25 Â 2.33 e grupo SS- 6.93 Â 2.12; p<0.0001;p=0.006) e NOx (Controle-2.25Â1.9; grupo SSHU-56.54 Â 9.15 e grupo SS 39.12 Â9.02; p<0.0001; p=0.001) nos pacientes em comparaÃÃo aos controles saudÃveis, e mais elevados no grupo SS em relaÃÃo ao grupo SSHU. Os pacientes com haplÃtipo Bantu/Bantu apresentaram maior concentraÃÃo de MCP-1, independente do uso de HU, seguido de Bantu/ Benin e Benin/Benin (p=0.01). Observou-se correlaÃÃo positiva entre os uma correlaÃÃo entre os nÃveis de MCP-1 e contagem de monÃcitos (p=0.004; r= 0.42); proteinÃria (p=0.002; r=0.43); albuminÃria (p=0.0004; r=0.47); TFG (p=0.02; r=0.32); MDA (p=0.02; r=0.32) e NOx (p=0.007; r= 0.38). CONCLUSÃO: Os resultados indicam que MCP-1 foi preditivo na detecÃÃo de alteraÃÃo renal, e que pode estar correlacionado ao dano causado pelo estresso oxidativo nos rins, evidenciado pelos altos nÃveis de MDA. Ainda, a HU parece ter reduzido o dano renal, visto que os pacientes em uso do fÃrmaco apresentaram nÃveis reduzidos desses parÃmetros.

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