Bone’s ability to resist fracture is often ignored until a low-energy fracture occurs. Patients with Chronic Kidney Disease (CKD) or osteoporosis are at an increased risk of low-energy fracture. Generally, fracture risk is evaluated by using a bone mineral density (BMD) test. BMD values; however, do not fully predict bone’s ability to resist fracture. This suggests that other parameters may be involved. Bone quality is the term used to describe these parameters, which are categorized into three groups: structural, material, and microdamage. The aim of this dissertation research was to examine whether bone quality was altered in patients who: 1) had abnormal bone turnover (high or low) due to CKD, 2) suffered a low-energy fracture despite normal BMD, or 3) had osteoporosis and were treated with bisphosphonates. These studies used iliac crest bone specimens from Caucasian females aged 21 to 87 years. Bone’s material parameters were measured by Fourier transform infrared spectroscopy. The key finding from the turnover study was that high and low turnover was associated with altered bone quality. Specifically, bone with high turnover had a lower mineral-to-matrix ratio compared to normal and low turnover (p<0.05), while low turnover had a lower cancellous bone volume and trabecular thickness compared to normal or high turnover (p<0.05). The key finding from the fracture study was that patients with normal BMD and low-energy fractures had altered bone quality (greater collagen crosslinking ratio) compared to patients who had low-BMD with low-energy fractures and healthy subjects (controls) (p<0.05). Lastly, the key findings from the bisphosphonate studies were that osteoporosis patients treated with these drugs had altered bone quality (specifically, greater (p<0.05) mineral-to-matrix ratio) compared to untreated turnover-matched osteoporotic patients, and that were several positive linear correlations with the nanoindentation derived Young’s modulus and hardness of cortical and trabecular bone and the duration of bisphosphonate treatment (p<0.05). The findings presented provide further evidence that bone quantity is not the sole factor in determining bone’s ability to resist fractures and that bone quality is an essential factor.

The incidence of chronic kidney disease (CKD) is increasing. CKD is characterized by a gradual decrease in renal function leading to end stage renal disease (ESRD). Damage to the glomerular podocytes, is one of the first hallmarks of CKD. We hypothesized that podocyte prostaglandin E2 (PGE2) receptors contribute to the progression of glomerular injury in models of CKD. To test this hypothesis, transgenic mice were generated with either podocyte-specific overexpression or deletion of the PGE2 EP4 receptor (EP4pod+and EP4pod-/- respectively). Mice were next tested in the 5/6 nephrectomy (5/6 Nx) or angiotensin II (Ang II) models of CKD. These studies revealed increased proteinuria and decreased survival for EP4pod+ mice while EP4pod-/- mice were protected against the development of glomerular injury. Furthermore, our findings were supported by in vitro studies using cultured mouse podocytes where an adhesion defect was uncovered for cells overexpressing the EP4 receptor. Additionally, our investigations have demonstrated a novel synergy between angiotensin II AT1 receptors and prostaglandin E2 EP4 receptors. This was revealed by in vitro studies using isolated mouse glomeruli. There we were able to show that Ang II stimulation leads to increased expression of cyclooxygenase 2 (COX-2), the enzyme responsible for synthesis of PGE2, in a p38 mitogen activated protein kinase (MAPK) dependent fashion. Moreover increased PGE2 synthesis was measured in response to Ang II stimulation. We confirmed the presence of this synergy in our cultured mouse podocytes and showed an adhesion defect in response to Ang II stimulation which was COX-2 and EP4 dependent. These findings suggest that Ang II AT1 receptors and PGE2 EP4 receptors act in concert to exacerbate glomerulopathies. Studies using mice with either podocyte-specific overexpression of a dominant negative p38 MAPK or mice with global deletion of the EP1 receptor did not provide conclusive results as to their respective signaling involvement in podocyte injury. Altogether our findings provide novel insight for podocyte PGE2 EP4 and Ang II AT1 receptor signaling in models of CKD. These studies provide novel avenues for pursuing therapeutic interventions for individuals with progressive kidney disease.

Relative changes are detectable in the blood of end-stage renal disease (ESRD) patients during hemodialysis (HD) treatment using optical spectroscopy. However, the potential impacts of several confounding factors that could affect the detection of these changes have not been evaluated. The objectives of this thesis were to: 1) investigate how the variations and/or changes in acid-base and oxygen parameters during HD treatment can affect the optical signature of whole blood of ESRD patients, 2) to investigate the effect of heparin on the optical properties of whole blood and its impact on our method. Blood samples were drawn from 23 ESRD patients at 5 time points during a 4 hour HD treatment and sent for blood gas and blood spectroscopy analyses. No significant correlations were found between the changes in the blood transmittance spectra and acid-base and oxygen parameters. This indicates that the perturbations in these parameters due to HD procedures do not confound the detection of changes in the blood transmittance spectra of ESRD patients during HD treatment. Additionally, the effect of heparin in modifying the optical properties of whole blood does not confound the detection of changes in the blood of ESRD patients due to HD treatment using whole blood-based optical spectroscopy. ANOVA revealed significant (P<0.05) measurable changes in the blood transmittance spectra of ESRD patients during HD treatment. Significant spectral differences (P<0.05) were found between ESRD patients. The lack of uniform spectral characteristics across patients is

Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide component of the renin angiotensin system and the endogenous ligand for the Mas receptor. Ang-(1-7) is generated mainly via angiotensin converting enzyme 2 (ACE2)-dependent cleavage of Angiotensin (Ang) II. Studies suggest Ang-(1-7) may protect against progression of renal injury in experimental models of chronic kidney disease, although the responses may be dose dependent. The role of Ang-(1-7) in the progression of renal fibrosis in unilateral ureteral obstruction (UUO) remains unclear. We tested the hypothesis that endogenous Ang-(1-7) and low dose exogenous Ang-(1-7) would protect against renal injury in the UUO model, while high dose Ang-(1-7) would exacerbate renal injury. Male C57Bl/6 mice underwent UUO and received vehicle, the Ang-(1-7) antagonist A779, or one of three doses of Ang-(1-7) for 10 days. Treatment with A779 exacerbated renal injury as seen by increased fibronectin, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) expression, increased tubulointerstitial fibrosis scores, macrophage infiltration, apoptosis, and NADPH oxidase activity in obstructed kidneys. Paradoxically, delivery of exogenous Ang-(1-7) was associated with increased renal injury regardless of dose. Taken together, these data indicate the Mas receptor may be sensitive to concentrations of Ang-(1-7) within the obstructed kidney and that exogenous Ang-(1-7) stimulates pro-fibrotic and pro-inflammatory signalling through unclear pathways.

Pea protein hydrolysate (PPH) has antihypertensive effects and prostanoids have been implicated in renal diseases. To investigate the role of PPH and prostanoids on renal and cardiovascular effects in cardio-renal disease, normal and diseased Han:SPRD-cy rats were given diets containing either 0, 0.5% or 1% PPH for 8 weeks. At termination, diseased rat kidneys displayed increased renal cyst growth, fibrosis, plasma creatinine and lower monocyte chemoattractant protein-1. Diseased rats also exhibited left ventricular (LV) hypertrophy, elevated systolic and diastolic blood pressures and LV end diastolic and systolic pressures. Four of five prostanoids were elevated in diseased rat kidneys. PPH attenuated systolic blood pressure, but not other components of the cardio-renal syndrome. PPH also increased select prostanoids in normal and diseased rats. Thus, dietary PPH attenuates hypertension in the Han:SPRD-cy rat, but does not ameliorate other components of disease, possibly due to increased prostanoid effects or an insufficient treatment length.

ABSTRACT IMPORTANCE: Age-related macular degeneration (AMD) is a leading cause of low vision in elderly population. The association of vascular and renal conditions has been reported inconsistently. Unfolding the association may provide the insight to eye care providers to take account general health management into eye care. OBJECTIVES: To investigate the prevalence of the vascular and renal comorbidities with AMD, examine the association of a single or combination of these comorbidities with AMD. DSIGN AND PARTICIPANTS: Population-base cross-sectional study involved the adults aged 40 years or older (N=4596) who participated in the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES), a national representative population-based survey of non-institutionalized US residents. MAIN OUTCOMES AND MEASURES: AMD was defined by the presence of drusen and presence of pigmental abnormality. Angina pectoris (AP), coronary heart disease (CHD), congestive heart failure (CHF) and myocardial infarction (MI), and stroke, assessed by self-report by the questionnaire of medical conditions, Chronic kidney disease (CKD), assessed by self-report and estimation of glomerular filtration rate (GFR) and the level of urine albumin. Heart disease (HD) was defined as having AP or CHF or CHD or MI. RESULTS: Among individuals with AMD, 6% had AP, 10% had CHD, 7% had CHF, 10% had MI, 13% had stroke, and 29% had CKD. The weighted prevalence of these conditions were significantly higher than those without AMD (All P-values CONCLUSION AND RELEVANCE: These findings from the nationally-representative sample of the US population highlight the prevalence of vascular and renal comorbidities associated with AMD, the modest evidence of relationship of each single comorbidity, and strong association of combination of stroke and CKD to AMD independent of age, gender, and other factors. Because of the cross-sectional design, the results of this study can not address a causal relationship between AMD and the examined comorbidities. It is unclear whether AMD and comorbidities arise from individual predisposition to vascular and renal diseases or whether complications from these morbidities increase the risk of AMD. However, the important caveat is that preventive and care management for the examined comorbidities may lessen the severity of symptoms or prevent AMD.

This work represents a significant contribution to the body of knowledge in the area of renal transplantation as it brings together the research related to policy analysis, empirical research, and cultural and religious issues related to organ donation and transplantation among South Asians in the UK. The candidate's work in this area is the first in the UK to systematically document and map a national picture of kidney transplant waiting lists and to identify and examine the complex reasons underlying how and why patient ethnicity impacts upon the likelihood of receiving a kidney transplant. The candidate has also developed a new evidence-base exploring the adequacies of the existing procurement arrangements and the implications of introducing any alternative policies within the context of a multi-ethnic and multifaith UK. Finally, the candidate's work has focused on developing an evidence-base of the public perceptions, attitudes, and religious viewpoints towards organ donation and transplantation among a cross-section ofthe South Asian population. The candidate's published works have been the foundation blocks for stimulating and informing the debate on the provision of renal transplant services for minority ethnic groups through the generation of an empirical evidence-base in a subject area which has traditionally relied upon anecdotal evidence. The evidence-base illuminates a very complex issue which has multi-faceted solutions that need to be addressed in different settings.

Made available in DSpace on 2014-06-11T19:23:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-12Bitstream added on 2014-06-13T19:29:45Z : No. of bitstreams: 1 moreira_lag_me_arafcf.pdf: 220588 bytes, checksum: cd403b75b05e1455d959138d5ab09209 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Universidade Estadual Paulista (UNESP) / Na avaliação de pacientes portadores de doença renal crônica, além da análise da alimentação ingerida é importante a análise da presença de produtos nitrogenados nos fluidos corporais como o sangue e urina, apresentando para este fim como grande potencial, a análise da saliva. Nesse sentido, uma das áreas relacionadas com a análise de alterações da composição bioquímica da saliva e que vem despertando o interesse, é a evolução clínica de pacientes portadores de doença renal, submetidos ou não a tratamento dialítico. Com base no contexto acima, a presente pesquisa teve por objetivo avaliar a saliva como meio de monitorar as variações dos compostos nitrogenados, em portadores desta patologia submetidos ao tratamento dialítico. No desenvolvimento da pesquisa foram avaliados a ingestão alimentar, a antropometria e os seguintes indicadores bioquímicos e físico-químicos: uréia, proteína total, aminoácidos, pH, e fluxo salivar. Foram encontrados nas determinações de uréia realizadas no soro, saliva não estimulada e saliva estimulada 136 mg/dl,107 mg/dl e 97 mg/dl antes da hemodiálise, respectivamente; e após a mesma, 39 mg/dl, 38,9 mg/dl e 36,0 mg/dl. As proteínas totais no soro, na saliva não estimulada e saliva estimulada apresentaram respectivamente valores de 7,0 g/dl, 0,30 g/dl; e 0,19 g/dl antes da hemodiálise e após a mesma, 9,0 g/dl, 0,22 g/dl e 0,20 g/dl. O pH salivar sofreu decréscimo após a hemodiálise. Os resultados obtidos permitem concluir que as proteínas totais na saliva e no soro não apresentaram comportamento semelhante. A hemodiálise atua sobre o pH salivar, mas não restabelece os níveis normais. A hemodiálise foi efetiva em reduzir a concentração dos compostos nitrogenados presentes na saliva / In the evaluation of patient carriers of chronic renal disease, besides the analysis of the ingested food, the analysis of the presence of nitrogenous products in the physical fluids like blood and urine and saliva are also important. In this sense, one of the areas of great scientific interest related to the analysis of biochemical composition alterations of saliva is the clinical evolution of patient carriers of renal disease, subjected or not to hemodialysis treatment. These studies can subsidize the development in the future of diagnoses methods for renal patients through the analysis of saliva. Based on the above context, this research aimed to evaluate saliva as a means of monitoring changes of nitrogen compounds in patients with renal disease undergoing dialysis. At the development of this research, food ingestion, the antropometria and the following biochemical and physical-chemical indicators were analyzed: urea, total protein, aminoacids, pH and salivary flow. The determinations of urea in the serum, of not stimulated saliva and of stimulated saliva were 136 mg/dl, 107 mg/dl and 97 mg/dl, respectively, before the hemodialysis, and after that, 39mg/dl, 38,9mg/dl and 36,0mg/dl. The total proteins in the serum, not stimulated saliva and stimulated saliva showed up 7,0 g/dl, 0,3 g/dl and 0,19 g/dl before the hemodialysis, respectively, and after that 9,0 g/dl, 0,22 g/dl and 0,20 g/dl. The saliva pH decreased after the hemodialysis. The obtained results allowed to conclude that the total proteins in the saliva and in the serum did not present similar behavior. The hemodialysis influences the salivary pH but does not restore it to normal levels. The hemodialysis was effective in the reduction of nitrogen compounds present in saliva

Submitted by CRISTIANE PARISOTO MASIERO null (cparisoto@uol.com.br) on 2018-04-03T14:43:56Z No. of bitstreams: 1 Cristiane Parisoto Masiero - Mestrado - 2018 versão final.pdf: 3444941 bytes, checksum: 319b20a2ac83b2c09f1e15a808f5a52b (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-04-03T16:53:25Z (GMT) No. of bitstreams: 1 masiero_cp_me_bot.pdf: 3444941 bytes, checksum: 319b20a2ac83b2c09f1e15a808f5a52b (MD5) / Made available in DSpace on 2018-04-03T16:53:25Z (GMT). No. of bitstreams: 1 masiero_cp_me_bot.pdf: 3444941 bytes, checksum: 319b20a2ac83b2c09f1e15a808f5a52b (MD5) Previous issue date: 2018-03-01 / RESUMO Introdução: A doença renal crônica é um problema de saúde pública global e vem apresentando uma tendência de crescimento. Quando a capacidade renal atinge parâmetros entre 10 e 15%, é necessária a realização de uma terapia renal substituitiva. No hospital em questão, o centro de hemodiálise se encontra com sua capacidade total instalada e a demanda por vagas continua. Os pacientes então começaram a ser internados aguardando pela vaga ambulatorial por períodos que podem chegar a 3 meses. A opção internação pela internação, que pareceu funcionar bem no início, logo criou novas interações antes inexistentes, além de consequências para os pacientes, como infecção hospitalar e depressão. Objetivo: Contribuir para a implementação de novas metodologias participativas na busca por soluções coletivas que atinjam os determinantes organizacionais nas atividades da área de saúde. Método: Foi utilizado o Laboratório de Mudanças (LM) que possui como base a teoria histórico cultural e o princípio da dupla estimulação e visa a construção coletiva de soluções. O trabalho foi dividido em duas fases: uma de coleta de dados etnográficos, com entrevistas individuais e coletivas, observação in loco e exame de documentos. Na segunda fase foram realizadas oito sessões do LM com um grupo composto em média por quinze pessoas do setor de terapia renal substitutiva e os setores que passaram a interagir após a internação dos pacientes. Resultados: A análise da atividade atual demonstrou que os pacientes com problemas renais continuam chegando ao hospital por diversas vias e que os profissionais não possuíam autonomia para negar o paciente pela falta de vaga. A equipe absorve essa demanda e sofre o impacto inicial é a que atende a insuficiência renal aguda (IRA) e equipe a de nefrologistas. Dados históricos demonstram que a equipe se manteve a mesma ao passo que o número de pacientes triplicou. Foram sendo arranjados locais para esses pacientes serem dialisados, ocupando outro setor, o do Centro de Terapia Intensiva (CTI), também com a capacidade esgotada. Essas mudanças levaram a contradições secundárias no sistema de atividade que emergiram durante as sessões do LM. As sessões proporcionaram um momento para discussão desses problemas, a mudança de alguns componentes do grupo para uma visão mais sistêmica da situação e a formação de agência de parte dos envolvidos. Após passar pelas fases de questionamento e construção histórica da atividade, houve a elaboração de proposta de novo modelo mais voltado para o método de diálise peritoneal, onde há maior autonomia do paciente, que pode realizar a diálise em sua casa. A prevenção também foi foco de discussão. Conclusão: O Laboratório de Mudanças proporcionou que os participantes ampliassem a compreensão dos problemas vivenciados pelo setor de hemodiálise de forma pessoal para sistêmica. Também possibilitou micro ciclos de aprendizagem expansiva, porém de forma diferente nos diversos atores. Houve a criação de agência manifestadas nas sessões e também fora dela. O LM demonstrou ser um importante método para a construção de mudanças organizacionais de forma coletiva. / ABSTRACT Introduction: Chronic kidney disease is a global public health problem and the tendency seems to increase. When renal capacity reaches parameters between 10 and 15%, renal replacement therapy is necessary. At the hospital in this study, the hemodialysis center has its full capacity installed and the demand for vacancies continues. The patients then began to be hospitalized waiting for the outpatient vacancy for periods that can reach 3 months. The hospitalization option, which seemed to work well in the beginning, soon created new interactions that did not exist before, as well as consequences for the patients, such as hospital infection and depression. Objective: To contribute to the implementation of new collaborative methodologies in the search for collective solutions of organizational determinants in health activities. Method: It was applied the Change Laboratory (CL) Method based on cultural historical theory and the principle of double stimulation that aims the collective construction of solutions. The study was divided in two phases: one of ethnographic data collection, with individual and collective interviews, on-site observation and documents examination. In the second phase eight CL sessions were performed with a group consisting of an average of fifteen people from the renal replacement therapy sector and the sectors that started to interact after the patients' hospitalization. Results: The analysis of the current activity demonstrated that patients with kidney problems continue arriving at the hospital through several routes and the hospital do not have the autonomy to deny the patient due to lack of space. The team absorbs this demand and suffers the initial impact is that it addresses acute renal failure (ARF) and team of nephrologists. Historical data demonstrate that the team remained the same while the number of patients tripled. Locations were set up for these patients to be dialyzed, occupying another sector, the Intensive Care Center (ICC), also with its full capacity. These changes led to secondary contradictions in the system of activity that emerged during CL sessions. The sessions provided a moment to discuss these problems and the change of some components of the group to a more systemic view of the situation and with the formation of agency on part of those involved. After the phases of questioning and historical construction of the activity, a proposal for a new model was developed that is more focused on the peritoneal dialysis method, that gives more autonomy for the patient, who can perform dialysis at home. Prevention was also on the focus of the discussion. Conclusion: The Change Laboratory Method provided the change in the understanding of the problems experienced by the hemodialysis sector in a personal to a systemic way. It also enabled micro cycles of expansive learning, but differently in different actors. There was the creation of agencies manifested in the sessions and also outside of them. CL has been shown to be an important method for building collective organizational changes.

Orientador: Ildeberto Muniz de Almeida / Resumo: RESUMO Introdução: A doença renal crônica é um problema de saúde pública global e vem apresentando uma tendência de crescimento. Quando a capacidade renal atinge parâmetros entre 10 e 15%, é necessária a realização de uma terapia renal substituitiva. No hospital em questão, o centro de hemodiálise se encontra com sua capacidade total instalada e a demanda por vagas continua. Os pacientes então começaram a ser internados aguardando pela vaga ambulatorial por períodos que podem chegar a 3 meses. A opção internação pela internação, que pareceu funcionar bem no início, logo criou novas interações antes inexistentes, além de consequências para os pacientes, como infecção hospitalar e depressão. Objetivo: Contribuir para a implementação de novas metodologias participativas na busca por soluções coletivas que atinjam os determinantes organizacionais nas atividades da área de saúde. Método: Foi utilizado o Laboratório de Mudanças (LM) que possui como base a teoria histórico cultural e o princípio da dupla estimulação e visa a construção coletiva de soluções. O trabalho foi dividido em duas fases: uma de coleta de dados etnográficos, com entrevistas individuais e coletivas, observação in loco e exame de documentos. Na segunda fase foram realizadas oito sessões do LM com um grupo composto em média por quinze pessoas do setor de terapia renal substitutiva e os setores que passaram a interagir após a internação dos pacientes. Resultados: A análise da atividade atual demonstrou que os pac... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: ABSTRACT Introduction: Chronic kidney disease is a global public health problem and the tendency seems to increase. When renal capacity reaches parameters between 10 and 15%, renal replacement therapy is necessary. At the hospital in this study, the hemodialysis center has its full capacity installed and the demand for vacancies continues. The patients then began to be hospitalized waiting for the outpatient vacancy for periods that can reach 3 months. The hospitalization option, which seemed to work well in the beginning, soon created new interactions that did not exist before, as well as consequences for the patients, such as hospital infection and depression. Objective: To contribute to the implementation of new collaborative methodologies in the search for collective solutions of organizational determinants in health activities. Method: It was applied the Change Laboratory (CL) Method based on cultural historical theory and the principle of double stimulation that aims the collective construction of solutions. The study was divided in two phases: one of ethnographic data collection, with individual and collective interviews, on-site observation and documents examination. In the second phase eight CL sessions were performed with a group consisting of an average of fifteen people from the renal replacement therapy sector and the sectors that started to interact after the patients' hospitalization. Results: The analysis of the current activity demonstrated that patients with... (Complete abstract click electronic access below) / Mestre