- 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.
Search results
Showing 111 to 119 of 119 (0.116 seconds)Spelling suggestions: "subject:"glomerular filtration"" "subject:"blomerular filtration""
| 111 |
Cohorte de patients avec le VIH/SIDA : échecs virologiques et effets de thérapies antirétrovirales sur la fonction rénale et l'hyperbilirubinémieLaprise, Claudie 03 1900 (has links)
Le virus de l'immunodéficience humaine (VIH) est à l’origine d’une infection chronique, elle-même responsable du développement du syndrome d'immunodéficience acquise (SIDA), un état de grande vulnérabilité où le corps humain est à la merci d’infections opportunistes pouvant s’avérer fatales. Aujourd’hui, 30 ans après la découverte du virus, même si aucun vaccin n’a réussi à contrôler la pandémie, la situation s’est grandement améliorée. Conséquemment à l’arrivée de traitements antirétroviraux hautement actifs (HAART) à la fin des années 1990, la mortalité associée au VIH/SIDA a diminué et un plus grand nombre de personnes vivent maintenant avec l'infection.
La présente thèse avait pour objectif d’aborder trois situations problématiques, en dépit de l’efficacité reconnue des HAART, plus particulièrement la faible charge virale persistante (LLV) et sa relation avec l’échec virologique, ainsi que les effets de certains antirétroviraux (ARV) sur les fonctions rénale et hépatique. Les objectifs précis étaient donc les suivants : 1) étudier le risque d’échec virologique à long terme chez les patients sous HAART dont la charge virale est indétectable comparativement aux patients affichant une LLV persistante; 2) évaluer sur le long terme la perte de fonction rénale associée à la prise de ténofovir (TDF) 3) étudier sur le long terme l'hyperbilirubinémie associée à la prise d’atazanavir (ATV) et ses autres déterminants possibles.
Afin d’atteindre les trois objectifs susmentionnés, une cohorte de 2 416 patients atteints du VIH/SIDA, suivis depuis juillet 1977 et résidant à Montréal, a été utilisée. Pour le premier objectif, les résultats obtenus ont montré un risque accru d’échec virologique établi à >1000 copies/ml d’ARN VIH chez tous les patients qui présentaient une LLV persistante de différentes catégories durant aussi peu que 6 mois. En effet, on a observé qu’une LLV de 50-199 copies/ml persistant pendant six mois doublait le risque d’échec virologique (Hazard ratio (HR)=2,22, Intervalle de confiance (CI) 95 %:1,60–3,09). Ces résultats pourraient modifier la façon dont on aborde actuellement la gestion des patients affichant une LLV, et plus particulièrement une LLV de 50-199 copies/ml, pour laquelle aucune recommandation clinique n’a encore été formulée en raison du manque de données. Pour le deuxième objectif, on a observé une augmentation du risque de perte de fonction rénale de l’ordre de 63 % (HR=1,63; 95% CI:1,26–2,10) chez les patients sous TDF comparativement aux patients traités avec d’autres ARV. La perte de fonction rénale directement attribuable à la prise de TDF, indique que cette perte est survenue au cours des premières années de l’exposition du patient au médicament. D’une perspective à long terme, cette perte est considérée comme modérée. Enfin, pour ce qui est du troisième objectif, on a constaté que l’incidence cumulative d’hyperbilirubinémie était très élevée chez les patients sous ATV, mais que cette dernière pouvait régresser lorsque l’on mettait fin au traitement. L’hyperbilirubinémie à long terme observée avec la prise d’ATV n’a été associée à aucun effet néfaste pour la santé.
Dans l’ensemble, la présente thèse a permis de mieux comprendre les trois situations problématiques susmentionnées, qui font actuellement l’objet de débats au sein de la communauté scientifique, et d’éclairer sous un jour nouveau la gestion des patients séropositifs sous traitement médicamenteux. / Human immonudeficiency virus (HIV) is a virus causing a chronic infection responsible for Acquired Immunodeficiency Syndrome (AIDS), a state of vulnerability of the body where different opportunistic infections will ultimately be fatal. About 30 years after the discovery of the virus, even if no vaccine is available to control the pandemia, situation has changed for the best. With the arrival of highly active anti-retroviral therapy (HAART) in the late 90's, a reduction in HIV/AIDS mortality rate and growing number of persons living with the infection were observed.
The overall objective of this thesis was to address three problematic situations, despite recognised HAART efficacy, especially low-level viremia (LLV) and its relationship with virologic failure, and the impacts of certain antiretrovirals (ARV) on kidney and hepatic functions. The specific objectives were: 1) to study the risk of virologic failure in long-term perspective in undetectable patients under HAART in comparison to patients with persistent LLV; 2) to evaluate the long-term loss of kidney function related to tenofovir (TDF) exposure 3) to evaluate long-term hyperbilirubinemia related to atazanavir (ATV) exposure and other possible determinants.
In order to address the three specific objectives, a cohort of patients 2416 living with HIV/AIDS followed in Montreal since July 1977 was used. For the first objective, analyses and results shown an increased risk of virological failure defined as >1000 copies/mL of HIV RNA, for all categories of persistent LLV as soon as 6 months of persistent duration. Persistent LLV of 50-199 copies/mL for 6 months doubled the risk of virologic failure (Hazard ratio (HR)=2,22, Confidence interval (CI) 95%: 1,60-3,09). The results shed new light for the management of patients with LLV, especially for LLV of 50-199 copies/mL, for which no clinical recommendation is currently available due to a lack of data. For the second objective, an increased risk of loss of kidney function of 63% (HR=1.63; 95% CI:1.26–2.10) associated to TDF exposure in comparison to patients taking other ARV was observed. The cumulative eGFR loss directly attribuable to TDF also shown that this loss occured during the first years of exposure. This loss was mild in a long-term perspective. For the third objective, it has been shown that the cumulative incidence of hyperbilirubinemia in ATV users was very high and that regression was possible if ATV exposure was ended. Long-term hyperbilirubinemia related to ATV use was not associated with adverse health outcome.
Overall, this thesis allowed a better understanding of these three problematics currently debated in scientific literature and shed new lights on management of HIV positive patients under therapy.
|
| 112 |
Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole / Administration of tenofovir during pregnancy in Wistar rats: effects on the offspringGois, Pedro Henrique França 31 October 2014 (has links)
Introdução: Tenofovir disoproxil fumarate (TDF) é um inibidor da transcriptase reversa análogo nucleotídeo que tem sido usado por gestantes para o tratamento da infecção pelo vírus da imunodeficiência humana (HIV), bem como para a prevenção da transmissão vertical do vírus. Até o momento, não há estudos experimentais ou em humanos sobre a incidência de alterações renais nos fetos expostos a esquemas contendo TDF. Objetivo: Verificar a ocorrência de alterações renais e sistêmicas fetais causadas pelo uso do TDF durante a gestação. Metodologia: Ratos Wistar fêmeas receberam dieta padrão com ou sem adição de TDF (100mg/Kg de dieta) desde uma semana antes do cruzamento até o parto. A prole proveniente do grupo TDF foi colocada com uma mãe adotiva não tratada durante o período de amamentação e foi comparada com a prole de ratas que receberam dieta padrão durante a gestação (grupo controle). Controle e TDF foram acompanhados até três (n=9 para cada grupo) e seis (n=12 e n=10, respectivamente) meses de idade. Foram avaliados: peso corporal (PC) e pressão arterial sistólica (PAS) mensais, contagem de glomérulos, função renal (através do clearance de inulina), parâmetros bioquímicos (proteinúria, colesterol total, sódio e potássio séricos e urinários), e expressão proteica do tecido renal para componentes do sistema renina angiotensina aldosterona (SRAA) e para transportadores de sódio. Resultados: A prole TDF apresentou menor PC ao nascimento em comparação com o controle. Após o 3º mês, o grupo TDF demonstrou um crescimento compensatório, atingindo o sexto mês com maior PC. O peso renal foi menor no grupo TDF, porém, não houve diferença do número de néfrons entre os grupos. O grupo TDF apresentou alterações estruturais glomerulares. Observou-se também um aumento progressivo da PAS após o segundo mês de idade no grupo TDF. Não houve diferença estatística na função renal entre os grupos. Os níveis plasmáticos de aldosterona foram mais elevados no grupo TDF, em associação com um aumento da expressão renal do SRAA. Ratos do grupo TDF apresentaram menor excreção renal de sódio e maior expressão renal de transportadores de sódio. Conclusões: Esta é a primeira descrição, a partir de um modelo experimental, que a utilização do TDF durante a gestação resulta em hiperativação do SRAA, aumento da expressão dos transportadores renais de sódio e hipertensão arterial da prole / Introduction: Tenofovir disoproxil fumarato (TDF) is a nucleotide reverse transcriptase inhibitor that has been used in pregnants for treatment of maternal HIV infection and for prevention of vertical transmission. Currently, there are no published studies providing data regarding the occurrence of renal abnormalities in fetuses exposed to TDF-containing regimens. Objective: To evaluate the occurrence of systemic and renal abnormalities in offspring of Wistar rats exposed to TDF during pregnancy. Methods: Female Wistar rats received a standard diet, with or without addition of TDF (100 mg/Kg diet), one week before mating and during pregnancy. Offspring from the TDF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and TDF were followed up at three and six months of age. Analyzed data: monthly body weight and systolic blood pressure (SBP), glomerular counting, renal function, biochemical parameters, and renal tissue immunoblotting for renin angiotensin aldosterone system (RAAS) and renal sodium transporters. Results: TDF offspring showed lower birth weight compared with the control group. After the third month, growth among the TDF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the TDF group. The nephron number did not differ between groups. The TDF group showed glomerular structural changes. There was no significant difference in renal function between the groups studied. Plasma aldosterone was higher in the TDF group, associated with a significant increase in renal expression of RAAS. The TDF rats showed upregulation of renal sodium transporters and consequently lower urinary sodium excretion. Conclusions: This is the first demonstration using an experimental model that maternal exposure to TDF during gestation results in over activation of RAAS, upregulation of renal sodium transporters and hypertension of the offspring
|
| 113 |
Mecanismos de lesão renal em ratos com deficiência de vitamina D submetidos ao tratamento com Tenofovir / Mechanisms of renal injury in vitamin D deficient rats treated with TenofovirCanale, Daniele 28 March 2014 (has links)
A Síndrome da Imunodeficiência Adquirida (AIDS) é um problema de saúde pública. O Tenofovir Disoproxil Fumarato (TDF) foi o primeiro inibidor do nucleotídeo da transcriptase reversa e é a droga mais recomendada para o tratamento da AIDS. Entretanto, o uso prolongado de TDF está associado com a nefrotoxicidade. A deficiência de vitamina D tem alta prevalência em indivíduos infectados com o Vírus da Imunodeficiência Humana (HIV). A vitamina D participa da regulação de atividades fisiológicas de diversos órgãos, incluindo o rim, oferecendo proteção contra as lesões ocasionadas por diferentes causas. Portanto, pacientes com níveis baixos de vitamina D infectados com o HIV podem apresentar complicações renais e cardiovasculares durante a terapia antirretroviral. Sendo assim, a carência desta vitamina pode acelerar a progressão da doença renal. Tendo em vista o aumento da incidência de hipovitaminose D na população mundial, esse trabalho tem o objetivo de verificar os mecanismos que levam ao desenvolvimento da lesão renal em ratos depletados de vitamina D submetidos ao tratamento com TDF. Ratos Wistar foram divididos em quatro grupos: controle, animais que receberam dieta padrão por 60 dias; dVD, animais que receberam dieta depletada em vitamina D por 60 dias; TDF, animais que receberam dieta padrão por 60 dias com a adição de TDF (50 mg/kg de dieta) nos últimos 30 dias; e dVD+TDF, animais que receberam dieta depletada em vitamina D por 60 dias com a adição de TDF nos últimos 30 dias. Ao final dos 60 dias, os animais foram submetidos à eutanásia, amostras de sangue, urina e o tecido renal foram coletados para a análise dos mecanismos de lesão renal. O tratamento com TDF levou a insuficiência renal observada pela queda da filtração glomerular e lesão tubular proximal com aparecimento de fosfatúria ocasionada pela diminuição do cotransportador sódio/fosfato subtipo IIa. Essas alterações foram acompanhadas de hipertensão e modificações no perfil lipídico. A deficiência em vitamina D associada à administração de TDF agravou os efeitos renovasculares e a nefrotoxicidade induzida pelo TDF, pelo menos em parte, devido ao aumento nos marcadores de estresse oxidativo e a participação do sistema renina-angiotensina-aldosterona. Portanto, é essencial monitorar os níveis de vitamina D em pacientes infectados com o HIV tratados com TDF / Acquired Immunodeficiency Syndrome (AIDS) has become one of the world\'s most serious health problem. Tenofovir Disoproxil Fumarate (TDF) was the first available nucleotidic reverse transcription inhibitor and is a widely prescribed antiretroviral medication for treatment of Human Immunodeficiency Virus (HIV). However, the long-term use of TDF has been associated with a number of toxicities, including those affecting the kidney. Vitamin D deficiency is prevalent among HIVinfected individuals. Vitamin D not only regulates numerous physiological activities of multiple organ systems, but also protects the kidney from injury from different causes. Thus, HIV-infected subjects with low levels of vitamin D could experience increased complications during antiretroviral therapy, such as cardiovascular disease and renal impairment. In view of the high worldwide incidence of hypovitaminosis D, the aim of this study was to investigate the effects of vitamin D deficiency on TDF-induced nephrotoxicity. Wistar rats were divided into four groups: control, receiving a standard diet for 60 days; dVD, receiving a vitamin D-free diet for 60 days; TDF, receiving a standard diet for 60 days with the addition of TDF (50 mg/kg food) for the last 30 days; and dVD+TDF receiving a vitamin D-free diet for 60 days with the addition of TDF for the last 30 days. At the end of the protocol, animals were euthanized and blood, urine and tissue samples were collected in order to evaluate the mechanisms responsible for renal injury. TDF led to impaired renal function, hyperphosphaturia, hypophosphatemia, hypertension and increased renal vascular resistance due to downregulation of the sodium-phosphorus cotransporter and upregulation of reninangiotensin- aldosterone system (RAAS). TDF also increased oxidative stress, as evidenced by higher TBARS and lower GSH levels, and induced dyslipidemia. Association of TDF and vitamin D deficiency aggravated renovascular effects and TDFinduced nephrotoxicity at least in part by the increase of oxidative stress and the involvement of RAAS. Hence, it is important to monitor vitamin D levels in HIV-infected patients treated with TDF
|
| 114 |
Cohorte de patients avec le VIH/SIDA : échecs virologiques et effets de thérapies antirétrovirales sur la fonction rénale et l'hyperbilirubinémieLaprise, Claudie 03 1900 (has links)
Le virus de l'immunodéficience humaine (VIH) est à l’origine d’une infection chronique, elle-même responsable du développement du syndrome d'immunodéficience acquise (SIDA), un état de grande vulnérabilité où le corps humain est à la merci d’infections opportunistes pouvant s’avérer fatales. Aujourd’hui, 30 ans après la découverte du virus, même si aucun vaccin n’a réussi à contrôler la pandémie, la situation s’est grandement améliorée. Conséquemment à l’arrivée de traitements antirétroviraux hautement actifs (HAART) à la fin des années 1990, la mortalité associée au VIH/SIDA a diminué et un plus grand nombre de personnes vivent maintenant avec l'infection.
La présente thèse avait pour objectif d’aborder trois situations problématiques, en dépit de l’efficacité reconnue des HAART, plus particulièrement la faible charge virale persistante (LLV) et sa relation avec l’échec virologique, ainsi que les effets de certains antirétroviraux (ARV) sur les fonctions rénale et hépatique. Les objectifs précis étaient donc les suivants : 1) étudier le risque d’échec virologique à long terme chez les patients sous HAART dont la charge virale est indétectable comparativement aux patients affichant une LLV persistante; 2) évaluer sur le long terme la perte de fonction rénale associée à la prise de ténofovir (TDF) 3) étudier sur le long terme l'hyperbilirubinémie associée à la prise d’atazanavir (ATV) et ses autres déterminants possibles.
Afin d’atteindre les trois objectifs susmentionnés, une cohorte de 2 416 patients atteints du VIH/SIDA, suivis depuis juillet 1977 et résidant à Montréal, a été utilisée. Pour le premier objectif, les résultats obtenus ont montré un risque accru d’échec virologique établi à >1000 copies/ml d’ARN VIH chez tous les patients qui présentaient une LLV persistante de différentes catégories durant aussi peu que 6 mois. En effet, on a observé qu’une LLV de 50-199 copies/ml persistant pendant six mois doublait le risque d’échec virologique (Hazard ratio (HR)=2,22, Intervalle de confiance (CI) 95 %:1,60–3,09). Ces résultats pourraient modifier la façon dont on aborde actuellement la gestion des patients affichant une LLV, et plus particulièrement une LLV de 50-199 copies/ml, pour laquelle aucune recommandation clinique n’a encore été formulée en raison du manque de données. Pour le deuxième objectif, on a observé une augmentation du risque de perte de fonction rénale de l’ordre de 63 % (HR=1,63; 95% CI:1,26–2,10) chez les patients sous TDF comparativement aux patients traités avec d’autres ARV. La perte de fonction rénale directement attribuable à la prise de TDF, indique que cette perte est survenue au cours des premières années de l’exposition du patient au médicament. D’une perspective à long terme, cette perte est considérée comme modérée. Enfin, pour ce qui est du troisième objectif, on a constaté que l’incidence cumulative d’hyperbilirubinémie était très élevée chez les patients sous ATV, mais que cette dernière pouvait régresser lorsque l’on mettait fin au traitement. L’hyperbilirubinémie à long terme observée avec la prise d’ATV n’a été associée à aucun effet néfaste pour la santé.
Dans l’ensemble, la présente thèse a permis de mieux comprendre les trois situations problématiques susmentionnées, qui font actuellement l’objet de débats au sein de la communauté scientifique, et d’éclairer sous un jour nouveau la gestion des patients séropositifs sous traitement médicamenteux. / Human immonudeficiency virus (HIV) is a virus causing a chronic infection responsible for Acquired Immunodeficiency Syndrome (AIDS), a state of vulnerability of the body where different opportunistic infections will ultimately be fatal. About 30 years after the discovery of the virus, even if no vaccine is available to control the pandemia, situation has changed for the best. With the arrival of highly active anti-retroviral therapy (HAART) in the late 90's, a reduction in HIV/AIDS mortality rate and growing number of persons living with the infection were observed.
The overall objective of this thesis was to address three problematic situations, despite recognised HAART efficacy, especially low-level viremia (LLV) and its relationship with virologic failure, and the impacts of certain antiretrovirals (ARV) on kidney and hepatic functions. The specific objectives were: 1) to study the risk of virologic failure in long-term perspective in undetectable patients under HAART in comparison to patients with persistent LLV; 2) to evaluate the long-term loss of kidney function related to tenofovir (TDF) exposure 3) to evaluate long-term hyperbilirubinemia related to atazanavir (ATV) exposure and other possible determinants.
In order to address the three specific objectives, a cohort of patients 2416 living with HIV/AIDS followed in Montreal since July 1977 was used. For the first objective, analyses and results shown an increased risk of virological failure defined as >1000 copies/mL of HIV RNA, for all categories of persistent LLV as soon as 6 months of persistent duration. Persistent LLV of 50-199 copies/mL for 6 months doubled the risk of virologic failure (Hazard ratio (HR)=2,22, Confidence interval (CI) 95%: 1,60-3,09). The results shed new light for the management of patients with LLV, especially for LLV of 50-199 copies/mL, for which no clinical recommendation is currently available due to a lack of data. For the second objective, an increased risk of loss of kidney function of 63% (HR=1.63; 95% CI:1.26–2.10) associated to TDF exposure in comparison to patients taking other ARV was observed. The cumulative eGFR loss directly attribuable to TDF also shown that this loss occured during the first years of exposure. This loss was mild in a long-term perspective. For the third objective, it has been shown that the cumulative incidence of hyperbilirubinemia in ATV users was very high and that regression was possible if ATV exposure was ended. Long-term hyperbilirubinemia related to ATV use was not associated with adverse health outcome.
Overall, this thesis allowed a better understanding of these three problematics currently debated in scientific literature and shed new lights on management of HIV positive patients under therapy.
|
| 115 |
Mecanismos de lesão renal em ratos com deficiência de vitamina D submetidos ao tratamento com Tenofovir / Mechanisms of renal injury in vitamin D deficient rats treated with TenofovirDaniele Canale 28 March 2014 (has links)
A Síndrome da Imunodeficiência Adquirida (AIDS) é um problema de saúde pública. O Tenofovir Disoproxil Fumarato (TDF) foi o primeiro inibidor do nucleotídeo da transcriptase reversa e é a droga mais recomendada para o tratamento da AIDS. Entretanto, o uso prolongado de TDF está associado com a nefrotoxicidade. A deficiência de vitamina D tem alta prevalência em indivíduos infectados com o Vírus da Imunodeficiência Humana (HIV). A vitamina D participa da regulação de atividades fisiológicas de diversos órgãos, incluindo o rim, oferecendo proteção contra as lesões ocasionadas por diferentes causas. Portanto, pacientes com níveis baixos de vitamina D infectados com o HIV podem apresentar complicações renais e cardiovasculares durante a terapia antirretroviral. Sendo assim, a carência desta vitamina pode acelerar a progressão da doença renal. Tendo em vista o aumento da incidência de hipovitaminose D na população mundial, esse trabalho tem o objetivo de verificar os mecanismos que levam ao desenvolvimento da lesão renal em ratos depletados de vitamina D submetidos ao tratamento com TDF. Ratos Wistar foram divididos em quatro grupos: controle, animais que receberam dieta padrão por 60 dias; dVD, animais que receberam dieta depletada em vitamina D por 60 dias; TDF, animais que receberam dieta padrão por 60 dias com a adição de TDF (50 mg/kg de dieta) nos últimos 30 dias; e dVD+TDF, animais que receberam dieta depletada em vitamina D por 60 dias com a adição de TDF nos últimos 30 dias. Ao final dos 60 dias, os animais foram submetidos à eutanásia, amostras de sangue, urina e o tecido renal foram coletados para a análise dos mecanismos de lesão renal. O tratamento com TDF levou a insuficiência renal observada pela queda da filtração glomerular e lesão tubular proximal com aparecimento de fosfatúria ocasionada pela diminuição do cotransportador sódio/fosfato subtipo IIa. Essas alterações foram acompanhadas de hipertensão e modificações no perfil lipídico. A deficiência em vitamina D associada à administração de TDF agravou os efeitos renovasculares e a nefrotoxicidade induzida pelo TDF, pelo menos em parte, devido ao aumento nos marcadores de estresse oxidativo e a participação do sistema renina-angiotensina-aldosterona. Portanto, é essencial monitorar os níveis de vitamina D em pacientes infectados com o HIV tratados com TDF / Acquired Immunodeficiency Syndrome (AIDS) has become one of the world\'s most serious health problem. Tenofovir Disoproxil Fumarate (TDF) was the first available nucleotidic reverse transcription inhibitor and is a widely prescribed antiretroviral medication for treatment of Human Immunodeficiency Virus (HIV). However, the long-term use of TDF has been associated with a number of toxicities, including those affecting the kidney. Vitamin D deficiency is prevalent among HIVinfected individuals. Vitamin D not only regulates numerous physiological activities of multiple organ systems, but also protects the kidney from injury from different causes. Thus, HIV-infected subjects with low levels of vitamin D could experience increased complications during antiretroviral therapy, such as cardiovascular disease and renal impairment. In view of the high worldwide incidence of hypovitaminosis D, the aim of this study was to investigate the effects of vitamin D deficiency on TDF-induced nephrotoxicity. Wistar rats were divided into four groups: control, receiving a standard diet for 60 days; dVD, receiving a vitamin D-free diet for 60 days; TDF, receiving a standard diet for 60 days with the addition of TDF (50 mg/kg food) for the last 30 days; and dVD+TDF receiving a vitamin D-free diet for 60 days with the addition of TDF for the last 30 days. At the end of the protocol, animals were euthanized and blood, urine and tissue samples were collected in order to evaluate the mechanisms responsible for renal injury. TDF led to impaired renal function, hyperphosphaturia, hypophosphatemia, hypertension and increased renal vascular resistance due to downregulation of the sodium-phosphorus cotransporter and upregulation of reninangiotensin- aldosterone system (RAAS). TDF also increased oxidative stress, as evidenced by higher TBARS and lower GSH levels, and induced dyslipidemia. Association of TDF and vitamin D deficiency aggravated renovascular effects and TDFinduced nephrotoxicity at least in part by the increase of oxidative stress and the involvement of RAAS. Hence, it is important to monitor vitamin D levels in HIV-infected patients treated with TDF
|
| 116 |
Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole / Administration of tenofovir during pregnancy in Wistar rats: effects on the offspringPedro Henrique França Gois 31 October 2014 (has links)
Introdução: Tenofovir disoproxil fumarate (TDF) é um inibidor da transcriptase reversa análogo nucleotídeo que tem sido usado por gestantes para o tratamento da infecção pelo vírus da imunodeficiência humana (HIV), bem como para a prevenção da transmissão vertical do vírus. Até o momento, não há estudos experimentais ou em humanos sobre a incidência de alterações renais nos fetos expostos a esquemas contendo TDF. Objetivo: Verificar a ocorrência de alterações renais e sistêmicas fetais causadas pelo uso do TDF durante a gestação. Metodologia: Ratos Wistar fêmeas receberam dieta padrão com ou sem adição de TDF (100mg/Kg de dieta) desde uma semana antes do cruzamento até o parto. A prole proveniente do grupo TDF foi colocada com uma mãe adotiva não tratada durante o período de amamentação e foi comparada com a prole de ratas que receberam dieta padrão durante a gestação (grupo controle). Controle e TDF foram acompanhados até três (n=9 para cada grupo) e seis (n=12 e n=10, respectivamente) meses de idade. Foram avaliados: peso corporal (PC) e pressão arterial sistólica (PAS) mensais, contagem de glomérulos, função renal (através do clearance de inulina), parâmetros bioquímicos (proteinúria, colesterol total, sódio e potássio séricos e urinários), e expressão proteica do tecido renal para componentes do sistema renina angiotensina aldosterona (SRAA) e para transportadores de sódio. Resultados: A prole TDF apresentou menor PC ao nascimento em comparação com o controle. Após o 3º mês, o grupo TDF demonstrou um crescimento compensatório, atingindo o sexto mês com maior PC. O peso renal foi menor no grupo TDF, porém, não houve diferença do número de néfrons entre os grupos. O grupo TDF apresentou alterações estruturais glomerulares. Observou-se também um aumento progressivo da PAS após o segundo mês de idade no grupo TDF. Não houve diferença estatística na função renal entre os grupos. Os níveis plasmáticos de aldosterona foram mais elevados no grupo TDF, em associação com um aumento da expressão renal do SRAA. Ratos do grupo TDF apresentaram menor excreção renal de sódio e maior expressão renal de transportadores de sódio. Conclusões: Esta é a primeira descrição, a partir de um modelo experimental, que a utilização do TDF durante a gestação resulta em hiperativação do SRAA, aumento da expressão dos transportadores renais de sódio e hipertensão arterial da prole / Introduction: Tenofovir disoproxil fumarato (TDF) is a nucleotide reverse transcriptase inhibitor that has been used in pregnants for treatment of maternal HIV infection and for prevention of vertical transmission. Currently, there are no published studies providing data regarding the occurrence of renal abnormalities in fetuses exposed to TDF-containing regimens. Objective: To evaluate the occurrence of systemic and renal abnormalities in offspring of Wistar rats exposed to TDF during pregnancy. Methods: Female Wistar rats received a standard diet, with or without addition of TDF (100 mg/Kg diet), one week before mating and during pregnancy. Offspring from the TDF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and TDF were followed up at three and six months of age. Analyzed data: monthly body weight and systolic blood pressure (SBP), glomerular counting, renal function, biochemical parameters, and renal tissue immunoblotting for renin angiotensin aldosterone system (RAAS) and renal sodium transporters. Results: TDF offspring showed lower birth weight compared with the control group. After the third month, growth among the TDF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the TDF group. The nephron number did not differ between groups. The TDF group showed glomerular structural changes. There was no significant difference in renal function between the groups studied. Plasma aldosterone was higher in the TDF group, associated with a significant increase in renal expression of RAAS. The TDF rats showed upregulation of renal sodium transporters and consequently lower urinary sodium excretion. Conclusions: This is the first demonstration using an experimental model that maternal exposure to TDF during gestation results in over activation of RAAS, upregulation of renal sodium transporters and hypertension of the offspring
|
| 117 |
BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
|
| 118 |
BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
|
| 119 |
BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
|
Page generated in 0.1346 seconds