Os pacientes acometidos pela insuficiência renal crônica apresentam diminuição progressiva da função renal associada à redução da taxa de filtração glomerular. Possuem a resposta imune celular e humoral suprimidas e a existência de quaisquer alterações de saúde bucal pode representar focos de infecção a esses pacientes, os quais são extremamente susceptíveis a estas. A doença periodontal é uma doença inflamatória destrutiva que afeta os tecidos periodontais, e estudos têm mostrado que a prevalência desta é maior em pacientes com IRC quando comparados com a população em geral. Objetivo: Avaliar os parâmetros clínicos da doença periodontal em pacientes com doença renal crônica. Métodos: Foi realizado exame clínico periodontal de 125 indivíduos com alteração renal crônica que foram divididos em grupo controle (GC), grupo pré-diálise (GPD) e grupo hemodiálise (GHD), e os grupos foram subdivididos de acordo com a doença periodontal. Resultados: A perda de inserção clínica foi maior nos grupos GPD e GHD quando comparados ao controle (p=0,0058; p=0,0383), os demais parâmetros periodontais não apresentaram diferenças significantes. Os níveis de ácido úrico e ferritina foram estatisticamente maiores nos GPD e GHD com quando comparados ao GC (p<0,001); p=0,008; p=0,01); o nível de PCR foi maior no grupo GPD quando comparados aos grupos GC e GHD (p<0,05); e os níveis de fibrinogênio e triglicerídeos foram maiores no grupo GPD com doença periodontal quando comparados ao GC (p=0,01, p=0,008), o mesmo não ocorreu com os grupos sem doença periodontal. Conclusão: Assim sendo, conclui-se que a PIC e o número de dentes ausentes foi maior nos grupos testes quando comparados ao controle. Portanto, os profissionais de saúde devem ter uma atenção maior aos pacientes que apresentam a DRC no sentido de efetuar uma relação interdisciplinar para melhorar a condição de saúde deste. / Chronic renal failure (CRF) is a progressive and irreversible loss of renal function associated with a decline in the glomerular filtration rate. CRFs patients have a humoral and cellular immune responses suppressed and the existence of any oral complications may be outbreaks of such patients, which are extremely susceptible to these. Periodontal disease is a destructive inflammatory disease affecting periodontal tissues, and studies have shown that this is greater prevalence in patients with CRF compared to the general population. Aim: The aim of this study was to assess the clinical periodontal parameters CRFs patients. Methods: 125 CRFs patients were included in the study, and they were divided in control group (GC), foregoing dialysis group (GPD), and hemodialysis group (GHD), and the groups were subdivided in accordance with periodontitis. Results: Clinical attachment loss (CAL) was greater in GPD and GHD groups compared to the control (p = 0.0383; p = 0.0058), the other periodontal parameters did not provide significant differences. Uric acid and ferritin levels were statistically higher in GPD and GHD when compared to the GC (p<0.05); the PCR level was higher in GPD group when compared to the GC and HDG groups (p<0.05); and fibrinogen and triglycerides levels were greatest in the GPD with periodontitis than the GC (p = 0.01, p = 0.008), the same did not occur with groups without periodontitis. Conclusion: Accordingly, it is concluded that the clinical attachment loss and the number of dental lost of the tests groups were larger than the control group. Therefore, healthcare professionals must have an attention to CFRs patients to make a relationship interdisciplinary to improve the health condition.

Thesis (M.Sc. (Physiology)) -- University of Limpopo, 2021 / The purpose of this study was to investigate the effect of cART on renal function and assess the association between renal function and cardiovascular risk factors in a black rural HIV-positive population in Limpopo Province, Mankweng district. We have conducted a cross-sectional study which included both male and female cART-treated patients (n=84), cART-naïve patients (n=27) and HIV-negative controls (n=44). We have measured biomarkers of renal function (plasma cystatin C, clusterin, retinol binding protein 4 [RBP4]) and determined the estimated glomerular filtration rate (eGFR) using the chronic kidney disease-epidemiology collaboration formula (CKD-EPI). We have also measured blood pressure (BP), body mass index (BMI) and fasting blood glucose (FBG). The prevalence of renal dysfunction was similar among the study groups. A significant difference in RBP4 was found among the groups after controlling for covariates (age, gender, alcohol consumption, BMI, systolic blood pressure and FBG) (F (2, 146) = [4.479], p=0.010). The significant difference in RBP4 was specifically observed between the cART-treated and cART-naïve groups (p=0.008). Cystatin C, clusterin and eGFR were not significantly different among the study groups after controlling for the covariates. The cardiovascular risk factors age (β=0.207; p=0.039), CD4+ T-cell count (β=-0.236; p=0.040), and duration of cART (β=0.232; p=0.043) were independently associated with cystatin C. The use of cART independently associated with RBP4 (β=0.282; p=0.004). Age (β=-0.363; p=0.001), CD4+ T-cell count (β=0.222; p=0.034) and duration of cART (β=-0.230; p=0.034) independently associated eGFR. Renal dysfunction is common in this HIV-positive population, with similar rates as the HIV-negative population. Plasma cystatin C as a promising alternative renal biomarker need to be re-evaluated in this HIV-positive population. RBP4 may be a more promising renal function biomarker in the HIV-positive population. Cardiovascular risk factors are associated with renal dysfunction in this rural HIV-positive population and CD4+ T-cell count may be an independent predictor for renal function.

Indiana University-Purdue University Indianapolis (IUPUI) / Polycystic kidney diseases (PKD) are genetic disorders characterized by fluid filled cysts in the kidney tubules and liver bile ducts. There are two forms of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). The focus of the studies in this thesis has been on ADPKD. The disease progresses slowly and the fluid-filled cysts grow in size due to increased rates of cell proliferation and fluid secretion into the cyst lumen. The expanding cysts compromise the normal kidney function and result in a decrease of renal function to the point of end-stage renal failure in midlife. Cyst enlargement is due, at least in part, to chloride secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Currently therapy is limited to renal cyst aspiration, dialysis, and eventually renal transplantation after organ failure, thus it has critical to determine possible drug therapies for the treatment of PKD. Previous studies showed that cyst fluid caused a secretory response in cells lining the cysts. We hypothesized that once the cyst have expanded and become so large that they burst or leak, which could also occur due to renal injury or aging, the cyst fluid may stimulate additional cyst growth. Lysophosphatidic Acid (LPA) was determined to be the active component of human cyst fluid, and we investigated the LPA stimulated signaling pathway. Our data suggest that the LPA stimulates chloride and fluid secretion by a combination of CFTR and Calcium-Activated chloride channels (CaCC) and that the two channels may functionally be linked to each other. The secretion is not occurring through a cAMP stimulated pathway, and it is possible that TMEM16A, a CaCC, plays a larger role than previously expected. Previous studies demonstrated that PPARγ agonists, insulin sensitizing drugs used to treat diabetes, inhibit chloride secretion by the collecting duct principal cells by decreasing CFTR synthesis. It was logical therefore to considered PPARγ agonists as long-term treatment for PKD. The first preclinical studied showed that high (20 mg/kg BW) dose pioglitazone, a PPARγ agonist, inhibited cyst growth in the PCK rat model, a slow progressing model, of PKD. To continue to look at the effects of the PPARγ agonists another preclinical study was completed, which tested if there was a class action of PPARγ agonists and if a lower dose was effective in treating the cystic burden. Using the PCK rat model, and another PPARγ agonist, rosiglitazone, a 24 week study was completed using 3 doses (4, 0.4, and 0.04 mg/kg BW). 4 mg/kg BW rosiglitazone is analogous to 20 mg/kg BW pioglitazone. The data indicated that the rosiglitazone is effective in lowering the cystic burden, and importantly the low dose proved to be effective. An additional rat model, the W-WPK rapidly progressing model was used to determine efficacy across multiple models, and to determine if there was a way to track the progress of the disease in a manner analogous to that used in human patients. The animals were treated with pioglitazone using 2 doses (2 and 20 mg/kg BW), and were imaged using CT scans to track the progress of the disease. The data suggest that pioglitazone was not as effective in the W-WPK rat model as it was the PCK rat model. There was a trend however, that low dose PPARγ agonist was as effective ad high dose. Even more important, the CT scans proved to be an effective way to track the progress of the disease in animal models.

The purpose of this study was to identify determinants of compliance behavior. Since compliance among dialysis patients increases survival rate, it is important for social workers to identify patients who are at risk of noncompliance.

Introduction : Les modèles murins sont grandement utilisés dans l’étude des maladies rénales et des pathologies associées. La concentration de la créatinine sérique est un bon indicateur de la filtration glomérulaire et en présence d’insuffisance rénale chronique (IRC), les concentrations de créatinine sérique (et la clairance) reflètent la sévérité de l’IRC. De plus, il a été démontré que l’IRC modifie le métabolisme des médicaments en diminuant l’activité et l’expression des enzymes hépatiques du cytochrome P450 (CYP450). Afin d’étudier la modulation du P450 par l’IRC avec un modèle murin et de confirmer nos résultats chez le rat, nous devons 1) développer un modèle d’IRC chez la souris, 2) mettre au point une technique de dosage des marqueurs de l’IRC et, 3) évaluer l’expression protéique du CYP450 en présence IRC. Matériel et Méthode : Trois modèles chirurgicaux d’IRC chez la souris ont été développés. Une méthode du dosage de la créatinine par chromatographie liquide à haute performance (CLHP) a été mise au point chez la souris et l’expression protéique du P450 a été mesurée par immunobuvardage de type Western. Résultats : Plusieurs paramètres de CLHP comme le pH, la concentration et le débit de la phase mobile modifient le pic d’élution et le temps de rétention de la créatinine. Concernant le modèle expérimental, on observe une perte de poids et une augmentation de la concentration plasmatique de la créatinine chez les souris avec une IRC. De plus, l’expression protéique de plusieurs isoformes du cytochrome P450 est modulée par l’IRC. Nous observons une diminution du CYP 2D de 42% (p < 0,01), du CYP 3A11 de 60% et du CYP 1A de 37% (p <0,01) par rapport aux souris témoins. On ne dénote aucun changement significatif au niveau de l’isoforme 2E1. Conclusion : Il est possible d’induire une insuffisance rénale chronique chez la souris suite à une néphrectomie. La technique de dosage de la créatinine par CLHP est précise et exacte et permet de caractériser la sévérité de l’IRC chez la souris. L’expression protéique du CYP450 est régulée à la baisse dans le foie des souris atteintes d’IRC. / Background: Mice models are widely used in renal studies. Seric creatinine concentration is used to evaluate glomerular filtration rate and is a good marker of chronic renal failure (CRF). It has been shown that CRF diminishes drug metabolism in the rat because of a downregulation of hepatic cytochrome P450 (CYP450) isoforms. To study CYP450 regulation in the mouse model, we needed to 1) develop a model of CRF in the mouse, 2) define a method of dosage of CRF markers, and 3) evaluate CYP450 protein expression in the liver of mice with CRF. Methods: Models of CRF were tested and sub-total nephrectomy was selected because of the efficacy and reproducibility to induce CRF. A high pressure liquid chromatography (HPLC) method for the dosage of creatinine in mice sera was developed. Liver protein expression of CYP1A1, CYP3A11, CYP2D and CYP2E1 was assessed by Western Blot analysis. Results: HPLC parameters such as pH, mobile phase concentration and flow rate modified the elution profile. Weight loss and high seric creatinine concentrations are seen in mice with CRF. Furthermore, protein expression of CYP1A, CYP3A11 and CYP2D was decreased in liver microsomes of mice with CRF by 37%, 60% and 42%, respectively (p<0.01) compared to sham-operated mice. We found no significant difference in the expression of CYP2E1. Conclusions: CRF models are reproducible in the mouse. The HPLC method for creatinine determination is precise and accurate, and can assess the severity of CRF. Hepatic protein expression of CYP450 is modulated in presence of CRF as in the rat.

L’insuffisance rénale chronique (IRC) est associée à une diminution de la clairance métabolique des médicaments résultant en partie de l’inhibition des cytochromes P450 (CYP450) et des enzymes de phase II, notamment la N-acétyltransférase 2 (NAT2), tel que démontré chez le rat. Nous avons précédemment démontré le rôle de l'hormone parathyroïdienne (PTH) dans la diminution des CYP450 hépatiques chez le rat souffrant d’IRC. Toutefois, l’étude des mécanismes sous-jacents pouvant être facilitée par l’utilisation de souris transgéniques, l’objectif de cette étude consiste à confirmer ces résultats dans un modèle murin. D’abord, afin de valider ce modèle expérimental, une IRC a été induite par néphrectomie subtotale 3/4 chez des souris C57BL/6, puis l’expression protéique et génique des CYP450 et de la Nat2 hépatiques a été étudiée. Les résultats indiquent que l’IRC induit effectivement une diminution d’expression de ces enzymes dans un modèle murin. Ensuite, des souris mutantes pour le gène codant la PTH (PTH-/-) et les souris correspondantes de type sauvage (PTH+/+) ont été néphrectomisées, puis l’expression protéique et génique des CYP450 hépatiques a été analysée. Si la PTH est responsable de la diminution du CYP450 en situation d’IRC, les souris PTH-/- atteintes d’IRC ne devraient présenter aucune baisse d’expression. Les résultats obtenus pour les souris PTH-/- ne peuvent être interprétés, puisque chez les souris PTH+/+ atteintes d'IRC, le CYP450 hépatique est inchangé par rapport aux souris PTH+/+ témoins. Des expériences supplémentaires seront requises afin de déterminer si la régulation à la baisse du CYP450 précédemment observée est contrecarrée par l’absence de PTH. / Chronic renal failure (CRF) is associated with a decrease in the metabolic clearance of drugs, which is partly due to a reduced expression of cytochrome P450 (CYP450) and phase II enzymes, namely N-acetyltransferase 2 (NAT2). This phenomenon has been shown in the rat. We have previously demonstrated the role of parathyroid hormone (PTH) in CYP450 down-regulation in rats with CRF. However, the study of mechanisms underlying the down-regulation of CYP450 by PTH should be confirmed with the use of knockout mice. The aim of this study was, therefore, to confirm these results in a murine model. Firstly, to validate this experimental model, CRF was produced in C57BL/6 mice using the 3/4 subtotal nephrectomy. Protein and mRNA levels of hepatic CYP450 and Nat2 were then analyzed. The results showed that CRF down-regulates these enzymes, as previously observed in the rat. Finally, PTH-null mice (PTH-/-) and their corresponding wild type (PTH+/+) were nephrectomized in order to analyze protein and mRNA expression of hepatic CYP450. If PTH is responsible for the decrease of CYP450 in the presence of CRF, then PTH-/- mice with CRF should not show any reduction in CYP450 expression compared to controls. The results concerning the PTH-/- mice could not be interpreted because PTH+/+ mice with CRF did not show any significant difference of CYP450 expression when compared to PTH+/+ controls. Thus, additional experiments must be conducted in order to determine the role of PTH in CYP450 down-regulation in CRF mice.

Introduction: Nous avons déjà montré que l’insuffisance rénale chronique (IRC) entraîne une régulation négative du cytochrome P450 (CYP450) dans le foie et l’intestin de rat. La présente étude cherche à déterminer l’effet de l’IRC sur l’expression des enzymes du CYP450 dans le cerveau de rat. L’expression génique, protéique ainsi que l’activité des isoenzymes du CYP450 ont été analysées dans différentes régions du cerveau (hippocampe, cervelet, cortex et parenchyme cérébral) afin de déterminer l’effet de l’insuffisance rénale chronique sur le métabolisme cérébral des médicaments par le CYP450. Méthodes: Le cerveau entier de rats atteints d’IRC (induite par une néphrectomie sub-totale 5/6) et de rats témoins (laparotomie blanche) a été disséqué en 4 parties (cortex, cervelet, hippocampe et parenchyme cérébral). L’expression protéique et celle de l’ARNm des isoformes 1A, 2C11, 2D, 3A et 4A du cytochrome P450 a été étudiée respectivement par immunobuvardage de type Western et PCR en Temps Réel. L’activité du CYP3A a été mesurée par le métabolisme du DFB en DFH sur des préparations de microsomes de cerveau. Une technique de culture cellulaire d’astrocytes a été mise au point et a permis d’évaluer l’expression des enzymes dans ces cellules suite à l’incubation des astrocytes avec le sérum de rats atteints d’insuffisance rénale chronique. Résultats: Chez les rats atteints d’IRC, les niveaux géniques de CYP1A, 2C et 3A sont diminués d’au moins 40% (p < 0,05) dans presque toutes les parties étudiées. Les niveaux d’ARNm du CYP2D demeurent inchangés. De plus, une diminution significative d’au moins 45% (p < 0,05) de l’expression protéique des CYP1A, 2C et 3A est observée dans presque toutes les structures étudiées. L’activité enzymatique de CYP3A est diminuée significativement dans le cerveau de rats IRC, ainsi que l’expression des enzymes du CYP2C11 dans les astrocytes en culture lorsqu’incubés avec du sérum de rat urémique. Conclusions: Ces études démontrent que le cerveau est également affecté par l’IRC. Ceci se traduit par une diminution de l’expression protéique, génique, ainsi que de l’activité des enzymes du CYP450. Cette diminution pourrait expliquer une augmentation des effets secondaires dans le système nerveux central en IRC. / Background: It has been shown that chronic renal failure (CRF) is associated with a downregulation of liver and intestinal cytochrome P450 (CYP450) in the rat. The present study aimed to investigate the repercussions of CRF on Brain. CYP450 isoenzymes mRNA and protein expression, as well as activity in different brain regions (cortex, cerebellum, hippocampus, and rest of brain parenchyma), have been studied in order to determine the effects of CRF on cerebral drug metabolism by CYP450. Methods: The entire brain of CRF rats (induced by 5/6th nephrectomy) and control rats (sham laparotomy) was dissected into 4 parts (cortex, cerebellum, hippocampus, and rest of brain parenchyma). Protein and mRNA expression of CYP1A, CYP2C, CYP2D, CYP3A, and CYP4A were assessed by Western Blot assay and Real Time PCR, respectively. CYP3A activity was assessed using DFB metabolism into DFH in brain microsomal preparation. Protein and mRNA expression were also assessed in cultured astrocytes incubated with serum from CRF rats. Results: In CRF rats, mRNA levels of CYP1A, CYP2C, and CYP3A were decreased significantly by at least 40% (p < 0.05) in almost all studied brain regions. Protein expression of these isoforms was decreased by at least 45% (p < 0.05) in almost all structures. A significant decrease in CYP3A activity was observed in the brain. The incubation of astrocytes with CRF sera induced a decrease in the protein and mRNA expression of the CYP2C11. Conclusions: CRF is associated with a decrease in some major drug-metabolizing enzymes, which could explain an increase in bioavailability of drugs in the brain.

L’insuffisance rénale chronique (IRC) est caractérisée par de multiples déséquilibres homéostatiques tels que la résistance à l’insuline. Peu d’études se sont intéressées aux mécanismes sous-jacents à cette résistance à l’insuline en IRC. De plus, il est méconnu si cette résistance à l’insuline peut mener au développement d’un diabète de type II chez des patients prédisposés. Dans un modèle d’IRC, le rat Sprague-Dawley (CD) néphrectomisé 5/6e, on observe une corrélation entre la gravité de l’atteinte rénale, évaluée par la créatinine sérique, et l’hyperglycémie, évaluée par la fructosamine sérique (R2 = 0.6982, p < 0.0001). Cependant, cet état hyperglycémique n’est pas observable lors d’une glycémie à jeun. Lors d’un test de tolérance au glucose, on observe une plus grande élévation de la glycémie (AUC 1.25 fois, p < 0.0001) chez le rat atteint d’IRC. Par contre, la sécrétion d’insuline au cours de ce même test n’augmente pas significativement (AUC ≈ 1.30 fois, N.S.) en comparaison aux rats témoins. Malgré une élévation des taux d’insuline en IRC suivant un bolus de glucose, les tissus périphériques ne montrent pas d’augmentation de la captation du glucose sanguin suggérant un défaut d’expression et/ou de fonction des transporteurs de glucose chez ces rats. En effet, on observe une diminution de ces transporteurs dans divers tissus impliqués dans le métabolisme du glucose tel que le foie (≈ 0.60 fois, p < 0.01) et le muscle (GLUT1 0.73 fois, p < 0.05; GLUT4 0.69 fois, p < 0.01). En conséquence, une diminution significative du transport insulinodépendant du glucose est observable dans le muscle des rats atteint d’IRC (≈ 0.63 fois, p < 0.0001). Puisque les muscles sont responsables de la majorité de la captation insulinodépendante du glucose, la diminution de l’expression du GLUT4 pourrait être associée à la résistance à l’insuline observée en IRC. La modulation de l’expression des transporteurs de glucose pourrait être à l’origine de la résistance à l’insuline en IRC. Cela dit, d’autres mécanismes peuvent aussi être impliqués. En dépit de cette importante perturbation du transport du glucose, nous n’avons pas observé de cas de diabète de type II chez le rat CD atteint d’IRC. Dans un modèle de rat atteint d’un syndrome métabolique, le rat Zucker Leprfa/fa, l’IRC provoque une forte hyperglycémie à jeun (1.5 fois, p < 0.0001). De plus, l’IRC chez le rat Zucker provoque une réponse glycémique (AUC 1.80 fois, p < 0.0001) exagérée lors d’un test de tolérance au glucose. Une forte résistance à l’insuline est mesurée au niveau des muscles puisque la dose usuelle d’insuline (2mU/mL) n’est pas suffisante pour stimuler la captation du glucose chez le rat Zucker atteint d’IRC. De plus, une modulation similaire des transporteurs de glucose peut être observée chez ces deux espèces. Par contre, environ 30% (p < 0.001) des rats Zucker atteints d’IRC avaient une glycosurie. L’IRC en soi ne mènerait donc pas au développement d’un diabète de type II. Par contre, lorsqu’une résistance à l’insuline est présente antérieurement au développement d’une IRC, cela pourrait précipiter l’apparition d’un diabète de type II chez ces patients prédisposés. / Chronic renal failure (CRF) is characterized by multiple homeostasis imbalances such as insulin resistance. However, few studies addressed the underlying mechanisms of the insulin resistance in CRF. Moreover, it is not known if the insulin resistance in CRF could lead to type II diabetes in predisposed patients. In 5/6th nephrectomised Sprague-Dawley (CD) rat model of CRF, we observed a correlation between the severity of the renal injury, evaluated by the serum creatinine level, and the hyperglycaemia, evaluated by the serum fructosamine level (R2 = 0.6982, p < 0.0001). However, this hyperglycemia is not observed on fasting. During a glucose tolerance test, we noticed an increase of the glycaemia in CRF rats (AUC 1.25 fold, p < 0.0001) comparing to controls. Insulin secretion of CRF rats was not significantly higher (AUC ≈1.30 fold, N.S.) during glucose challenge. Interestingly, despite more increase in insulin levels in CRF rats following a glucose bolus, the peripheral tissues did not show any increase in blood glucose uptake suggesting a defect in expression and/or function of glucose transporters in these rats. Indeed, we observed decreased expression of glucose transporters in the liver (≈0.60 fold, p < 0.01) and muscles (GLUT1 0.73 fold, p < 0.05 and GLUT4 0.69 fold, p < 0.01). Accordingly, there was a significant reduction in the insulin-dependent glucose uptake in the muscles of CRF rats compared to controls (≈0.63 fold, p < 0.0001). Since muscles are responsible for the majority of insulin-sensitive glucose transport, downregulation of GLUT4 could be associated with the insulin resistance observed in CRF. The modulation of the expression of several glucose transporters may contribute to insulin resistance in CRF, but other mechanisms could also be implicated. Despite this important perturbation of glucose transport, we did not observed any case of type II diabetes in our CD rat model. In a rat model of metabolic syndrome, the Zucker Leprfa/fa, CRF causes a strong hyperglycemia on fasting (1.5 fold, p < 0.0001). Furthermore, CRF Zucker showed an exacerbated glycemic response (AUC 1.80 fold, p < 0.0001) during glucose challenge. A strong insulin resistance in muscle was measured as the usual insulin dose (2mU/mL) was not enough to stimulate glucose uptake in Zucker rats with CRF. The same modulation of glucose transporters in the peripheral tissues was observed in both rat models. As opposed to CD rats, ≈30% (p < 0.05) of CRF Zucker rats’ showed presence of glucose in their urine. CRF by itself won’t lead to type II diabetes. However, when insulin resistance is already present when developing CRF, it could precipitate the onset of type II diabetes among these patients.

The diploma thesis deals with the emotional experience of patients with chronic renal failure. It aims to explore positive and negative emotional experiences, the presence of depressive and anxiety symptoms, the degree of anger and alexithymia in patients with chronic renal failure undergoing hemodialysis. The theoretical part summarizes previously published theoretical knowledge in this area and the empirical part describes the statistical measurement and comparison of selected variables of emotional experience in the research sample. The theoretical part is divided into 4 chapters, the first of them deals with the medical aspects of chronic renal failure and its treatment. The second chapter deals with the coping with illness, defines psychological aspects of chronic disease and describes the patient's subjective perception of the disease and attitudes towards the disease. The third chapter summarizes the definitions of emotions and emotional experience and defines the most respected theories of emotion. The fourth chapter describes the emotional experiences of illness, factors affecting the emotional experience of illness and deals with depression, anxiety, anger and alexithymia, at the end focuses on current research in this area. The empirical part is devoted to the empirical investigation of...

Made available in DSpace on 2016-01-26T12:51:30Z (GMT). No. of bitstreams: 1 heloisacaldas_tese.pdf: 13961449 bytes, checksum: adc041656d053c466bd2f0851119388c (MD5) Previous issue date: 2011-07-26 / Chronic renal failure (CRF) is characterized by progressive and irreversible loss of renal function and its treatment generates significant public spending for maintenance and care of patients on dialysis. Stem cell (SC) therapy, in its potential for treatment of chronic diseases, may be a promising strategy for repairing the damage from or slowing the progression of CRF. There are questions about cell type, quantity of cells, method and ideal place for deployment of SC and the role it plays in the repair of renal parenchyma. Objective: 1) To evaluate the effect of infusion of bone marrow derived cells (BMDC) in the treatment of experimental CRF; 2) Evaluate the combined effect of SC and biomaterial (BM) in the progression of CRF and study the effect of this therapy in different stages of CRF; 3) Evaluate the development of techniques for isolation and cultivation of human umbilical cord blood (HUCB) mesenchymal cells. Methods: Article 1: We used the 5/6 mass reduction model to induce experimental CRF. Kidney function was measured at the beginning of the experiment and 60 and 120 days after the surgery; Article 2: Animals were subdivided as to the amount of renal parenchyma injured (5/6 or 2/3), the use of BM as a scaffold to cell implantation, and cell type used (mononuclear or mesenchymal cells). Renal function was evaluated on days 0, 45, and 90 after surgery. Histological and immunohistochemical analyses were done in all groups at the end of the study; Article 3: Ten samples of HUCB were used and two different procedures for cultivation of mesenchymal stem cells (MSC) were tested: without Ficoll-Paque density gradient, to obtain nucleated cells; with Ficoll-Paque density gradient, for obtaining mononuclear cells. Results: Article 1: CRF progression analysis showed that treatment with BMDC significantly reduced the rate of decline of creatinine clearance (Clcr) when compared with the control group; Article 2:Treated animals showed significantly lower increases in serum creatinine and 24 hour proteinuria, and higher increases in Clcr after 90 days when compared to control animals in both models of CRF; Article 3: The MSC in culture from the method without Ficoll-Paque density gradient maintained growth forming confluent cell foci. Conclusions: Article 1: Progression of CRF can be delayed by injection of BMDC in the renal parenchyma; Article 2: a) Use of SC combined with BM can be an alternative way to administer BMDC; b) Cell therapy seems to be most effective when administered in less severe stages of CRF; Article 3: Nucleated cells without using Ficoll-Paque density gradient showed more efficiency in the cultivation of MSC from HUCB when compared with the procedure employing Ficoll-Paque density gradient / A insuficiência renal crônica (IRC) é caracterizada pela perda progressiva e irreversível da função renal e seu tratamento gera um gasto público significativo para manutenção de pacientes em tratamento dialítico. A terapia com células-tronco (CT), pelo seu potencial de tratamento das doenças crônicas, pode ser uma estratégia promissora para reparar ou retardar a progressão da IRC. Existem dúvidas sobre o tipo celular, a quantidade de células, o método e local ideal para implantação das CT e o papel por elas desempenhado na reparação do parênquima renal. Objetivos: 1) avaliar o efeito da infusão de células derivadas da medula óssea (CDMO) no tratamento da IRC experimental; 2) avaliar o efeito combinado das CT e biomaterial (BM) na progressão da IRC e estudar o efeito dessa terapia em diferentes estágios da IRC; 3) Avaliar o desenvolvimento de técnicas de isolamento e cultivo de células mesenquimais do sangue de cordão umbilical humano (SCU). Métodos: artigo 1: usamos o modelo de redução de massa 5/6 para induzir a IRC experimental. Função renal foi medida no início do experimento e 60 e 120 dias depois da cirurgia; artigo 2: animais foram subdivididos conforme a quantidade de parênquima renal lesado (5/6 ou 2/3), o uso de BM como arcabouço para o implante celular e o tipo de células utilizado (célula mononuclear ou mesenquimal). A função renal foi avaliada nos dias 0, 45 e 90 após cirurgia. Análise histológica e imunohistoquimica foram realizadas em todos os grupos ao final do estudo; artigo 3: Foram utilizadas dez amostras de SCU e testados dois diferentes procedimentos para cultivo de células-tronco mesenquimal (CTM): sem gradiente de densidade Ficoll-Paque, para obtenção de células nucleadas; por gradiente de densidade Ficoll-Paque, para obtenção de células mononucleares. Resultados: artigo 1: Análises da progressão da IRC mostraram que o tratamento com CDMO reduziu significativamente a taxa de declínio do clearance ( Clcr) quando comparados com o grupo controle; artigo 2: animais tratados apresentaram aumentos significativamente menores de creatinina sérica, proteinúria e Clcr maiores após 90 dias, quando comparado aos animais controles em ambos os modelos de IRC; artigo 3: as CTM em cultura provenientes do método sem gradiente de densidade Ficoll- Paque mantiveram o crescimento formando focos confluentes de células. Conclusões: artigo 1: a progressão da IRC pode ser retardada pela injeção de CDMO no parênquima renal; artigo 2: a) utilização da CT combinada com o BM pode ser uma via alternativa para administrar a CTMO; b) terapia celular parece ser mais eficaz quando administrada em estágios menos graves da IRC; artigo 3: As células nucleadas sem uso do gradiente de densidade Ficoll-Paque mostraram mais eficiente para o cultivo de CTM do SCU quando comparado ao procedimento com gradiente de densidade Ficoll-Paque.