Thesis (Ph. D.)--University of Wisconsin--Madison, 1957. / Typescript. Abstracted in dissertation abstracts, v. 16 (1956) no. 11, p. 2020-2021. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 169-175).

Hyperuricemia and local temperature changes in the joints of the extremities are known to be responsible, in part, for the development of gouty arthritis. No satisfactory explanation is yet available for (1) the selective deposition of monosodium urate monohydrate (MSUM) crystals in connective tissues (2) the increased incidence of gout in the later years of life and (3) the increased incidence of MSUM crystal deposition in connective tissues after trauma and in joints with preexisting disease. It is possible that the alterations in composition of the non-fibrillar matrix of cartilage and synovial fluid which are thought to occur with ageing, trauma or preexisting disease, may predispose these tissues to crystal deposition. The objectives of this study were to determine the effect of the cartilage and synovial fluid components, chondroitin sulfate, hyaluronic acid, proteoglycan monomer, proteoglycan aggregate, phospholipids and albumin on the growth of MSUM. The degradation of MSUM solutions was studied under sterile and non-sterile conditions to determine the possible causes of degradation and to define the time span of crystal growth experiments. The rate of degradation of MSUM solutions increased with an increase in temperature. The concentration of MSUM in solution fell sharply after autoclaving and solutions stored in containers with rubber closures showed greater degradation of MSUM than autoclaved solutions stored in all-glass containers. Rubber stoppers apparently absorbed MSUM from solution. The degradation of MSUM solutions was thought to be due to both bacterial consumption and chemical decomposition in non-sterile solutions but was due only to chemical decomposition in sterile solutions. The aqueous solubility of MSUM was determined at different temperatures and in the presence of varying concentrations of sodium chloride. Sodium chloride suppressed MSUM solubility. The aqueous solubility of MSUM was also determined in the presence of several connective tissue components at 37°. Chondroitin sulfate (CS) decreased the saturation solubility of MSUM probably due to the sodium present in the CS samples. Proteoglycan aggregate, proteoglycan monomer, hyaluronic acid an albumin resulted in very slight increases in the solubility of MSUM. The growth kinetics of MSUM was studied using the seeded growth technique. An equation of the general form: [formula omitted] was used to determine the overall growth rate constant, [formula omitted]. Linear plots of the integrated form of the second order growth equation gave the best fit between the points and gave reasonably constant values for [formula omitted] determined at a given initial supersaturation concentration and varying seed amounts. An induction period or a period of slow growth was observed at both the initial supersaturation concentrations studied. The length of the induction period was inversely proportional to the added seed amount. Differing concentrations of additives were included in the growth medium and K' determined. Chondroitin sulfate (CS) significantly increased the growth rate constant for MSUM growth. However, the proportion of CS decreases in aged and osteoarthritic cartilage and thus a decreasing proportion of a growth accelerator is unlikely to be a factor in the deposition of MSUM in cartilage. CS has been found in the synovial fluid of arthritic joints and may act as an MSUM growth accelerator in this medium. Hyaluronic acid (HA) and albumin caused significant inhibition of the growth of MSUM crystals. This effect may be due to the adsorption of these molecules onto the MSUM seed crystals resulting in the poisoning of the active growth sites on the crystal surface. Cartilage HA and synovial fluid albumin levels are increased in aged and/or diseased joints. Increased proportions of growth inhibitors do not offer likely explanations of crystal deposition in joint tissues. At concentrations of 0.1-1.0 mg mL⁻¹ proteoglycan monomer (PGM) and proteoglycan aggregate (PGA) slightly increased the MSUM growth rate constant but this increase was statistically insignificant. The two phospholipids, phosphatidylcholine and phospha-tidylserine increased the growth rate constant of MSUM. Phosphatidylserine, however, did not significantly increase the growth rate constant at the concentrations studied. It is possible that the raised levels of phospholipids in aged or diseased cartilage and synovial fluid could accelerate the growth of MSUM crystals resulting in MSUM deposition in these tissues. / Pharmaceutical Sciences, Faculty of / Graduate

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains vii, 51 p. : ill. Includes abstract. Includes bibliographical references.

Laboratory serum biochemical tests are regarded by the Liver Study Group (LSG) of the WSAVA as an essential component of any liver investigation. The LSG categorised liver disease into four groups: vascular disorders, biliary disorders; parenchymal disorders and neoplasia. The laboratory tests that evaluate the liver have three categories. The cytosolic enzymes assess hepatocellular integrity; the cholestatic or inducible enzymes assess the biliary tree, liver excretory pathways and possible enzyme induction. The third category is the liver function tests which assess overall hepatic functional mass and portovascular integrity. The liver function tests commonly used include plasma ammonia concentration, serum bile acid concentrations and various tests that evaluate the uptake and conjugation of metabolites by the liver. Uric acid was once used as a liver test in the late 1950’s early 1960’s. Physiologically, uric acid is an attractive candidate for a liver function test. In most mammalian species serum uric acid levels only increase to the levels encountered in humans when there is hepatic dysfunction. Uric acid fell out of favour as a liver function test following the publication of two studies and one case report in the late 1950’s. The differences between hepatocellular integrity tests, cholestatic tests and tests of liver function were not fully understood at that time. The authors unfairly compared uric acid, essentially a liver function test, to a test of cholestasis. In addition the authors had very vague inclusion criteria for their liver disease cases. Despite the short-comings in these studies several prominent reference texts have since perpetuated their findings and uric acid fell out of the reckoning as a test of liver function. Many tests of liver function have been used over the years. Dynamic function tests have gained popularity again. Plasma ammonia concentration is a very reliable test of liver function but has very stringent sample-handling requirements which often make its application in the average clinic setting impractical. Serum bile acid concentrations, while not as sensitive or specific for portovascular shunting as ammonia, are widely regarded as the best test of overall liver function, especially with respect to non vascular-associated liver disease. However bile acid assays are not widely available in South Africa resulting in delays in turn-around times. In today’s climate of ever increasing costs, and demand for rapid turn around times, it would be very useful to veterinarians if a simple, rapid, cheap and robust assay could be found for evaluating functional hepatic mass. Uric acid would seem to have this potential and it is performed by most medical laboratories. In this study the serum uric acid concentrations and concentration of bile acids of a control group of normal dogs was used to compare to those in three other groups of dogs. Two of these groups had liver disease, and the third was a renal disease group. The one group of liver disease was comprised of dogs with congenital vascular anomalies while the second liver disease group was made up of dogs with various parenchymal liver diseases. Serum bile acid concentrations in the four groups were compared to the serum uric acid levels to assess the utility of uric acid as a test of liver function; and to measure the affects of diminished renal function on serum uric acid concentrations. There were significant differences in the serum bile acid concentrations between the two liver disease groups and the non-liver disease groups. Uric acid concentrations between all four groups did not differ significantly however. Serum uric acid was elevated in dogs with renal impairment. Therefore the findings in this study indicate that uric acid cannot be used as a test of liver function and is not comparable to serum bile acids in this regard. Copyright / Dissertation (MMedVet)--University of Pretoria, 2009. / Companion Animal Clinical Studies / unrestricted

No description available.

Thesis (M.S.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains vii, 88 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

This work is a quantitative description of the renal excretion and the post-renal modification of ureteral urine from native (unanesthetized, uninfused, and normal hydropenic) desert quail, Lophortyx gambelii. The technique used in this study establishes the glomerular filtration rate (GFR), urine flow rate, and urinary excretion of water, sodium, potassium, and uric acid for desert quail in a relatively undisturbed state and in steady-state balance with regard to intake and output of water, sodium, and potassium. In contrast, conventional methods of determining GFR in birds include the use of anesthesia, cloacal or ureteral canulation, and infusion of fluids to introduce filtration markers (e.g. inulin) and to cause a diuresis (e.g. by using mannitol). In the present study, native desert quail had a urine flow rate of about 40 g/kg.day compared to over 500 g/kg.day for desert quail previously studied using conventional methods. Also in the present study, GFR was about 1.6 ml/kg.min which is about 25% lower than previously reported (2.1 ml/kg.min) for desert quail studied with conventional techniques. Renal absorption of the filtered loads of water, sodium and potassium also was determined in the present study. The fractions of the filtered loads reabsorbed by the renal tubules were: for water 98%, for sodium 99.4%, and for potassium 42%. These findings illustrate that renal reabsorption of these filtered substances is less complete in birds than in mammals where, in man for example, about 99% of the water and 99.8% of the sodium are normally reabsorbed. In addition, this study evaluates the role of the cloaca and lower intestines in changing the composition of the ureteral urine. Ureteral urine is modified in the cloaca and lower intestines of the desert quail before being excreted with the final droppings. This modification results in reabsorption of about 70% of the water and sodium and about 80% of the potassium in the ureteral urine. Thus for the desert quail, post-renal reabsorption of water and sodium from ureteral urine produced by the kidneys increases the total amounts of the filtered loads reabsorbed to 99% for water and 99.7% for sodium, which are nearly the same as seen for man. It is concluded that post-renal reabsorption of water and sodium is an important aspect of fluid and electrolyte balance in native desert quail. About 65% of the uric acid present in the ureteral urine was found to be degraded during its passage into the lower intestines. This is particularly significant because trapping of sodium and potassium occurs within the uric acid precipitates which form in bird urine. It was determined that about 20% of the sodium and 33% of the potassium in the ureteral urine are trapped within uric acid precipitates. Degradation of uric acid may increase the reabsorbable pools of these cations and facilitate their reabsorption by the tissues of the lower intestines. Since the intestinal ceca of birds contain large populations of uric acid-decomposing bacteria, and because other studies have suggested large amounts of water are reabsorbed in the ceca of birds, the role of the ceca in post-renal modification of urine was evaluated. The results are not conclusive. Cecaectomized (Cx) birds showed only a transitory increase in water loss when compared to sham operated (Sh) birds. No difference in uric acid excretion was seen between Cx or Sh birds. Thus, no obligatory role for the ceca in post-renal reabsorption of water and electrolytes, or in degradation of uric acid, was evident.

No description available.

SILVA, Agmael Mendonça. Estudo teórico das propriedades estruturais, eletrônicas e vibracionais de pontos quânticos de silício e grafeno e cálculos no formalismo DFT aplicados a cristais de ácido úrico. 2010. 148 f. Dissertação (Mestrado em Física) - Programa de Pós-Graduação em Física, Departamento de Física, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2010. / Submitted by Edvander Pires (edvanderpires@gmail.com) on 2015-10-15T18:26:42Z No. of bitstreams: 1 2010_dis_amsilva.pdf: 13243236 bytes, checksum: 7a9affef7c51dfd265b97f3957b677d3 (MD5) / Approved for entry into archive by Edvander Pires(edvanderpires@gmail.com) on 2015-10-21T20:33:13Z (GMT) No. of bitstreams: 1 2010_dis_amsilva.pdf: 13243236 bytes, checksum: 7a9affef7c51dfd265b97f3957b677d3 (MD5) / Made available in DSpace on 2015-10-21T20:33:13Z (GMT). No. of bitstreams: 1 2010_dis_amsilva.pdf: 13243236 bytes, checksum: 7a9affef7c51dfd265b97f3957b677d3 (MD5) Previous issue date: 2010 / There is a great interest in understanding the electronic properties of nano-structured materials aiming the development of new nano devices, especially how to modify the electronic properties of nano structures already known in a controlled manner. This work shows our studies, which were made in a pure atomistic way by computational simulation, on the electronic, optical and vibrational properties of (a) spherical quantum dots, silicon solid and hollow ones, (b) graphene nanoflakes and (c) crystals of uric acid, anhydrous, mono and dihydrate ones, using methods of Molecular Dynamics, Semiempirical, DFTB+ and DFT. We used the software called AMPAC and the modules of Materials Studio (Accelrys), the Forcite, CASTEP, Gulp and Dmol3 that are states of art in atomistic simulations. From the classical point of view we used Brenner force fields, which allow the formation and breaking of covalent bonds; and from the quantum dots of view, we used the method of density functional and DFTB+. In the study of silicon quantum dots, it was obtained a decrease of the energy gap due to the increase of the radius for massive dots, and contrary behavior to the hollow dots, when we fixed one point and varied only the radius of the hole. In relation to the graphene nanoflakes, it was obtained the stability of structures by the Dynamics Molecular, verifying that they keep their flattened form up to 1000 K; over 3400 K structures begin to have their links broken. The HOMO-LUMO energy gaps are sensitive to edges. Analysis of spin states revealed that only the triangular nanoflakes with zigzag edge have excess of electrons with alpha spin, however symmetry dependent. The modes of vibration for structures with nC ~ 50 were obtained and it was observed that rectangular nanoflake displays absorption bands in common with zigzag nanoflakes in two ranges of the infrared spectrum. Finally for the uric acid crystals, we observed that the lattice parameters for the dihydrate crystal are less consistent with experimental values. The gap of the crystal of uric acid, anhydrous and mono ones, is direct (~ 3.18 eV and 3.16 eV, respectively) and of the dihydrate is indirect (~ 2.89 eV). The 2p orbitals are the largest contributors to the density of states. Water has great influence in the conduction band of the dihydrate crystal. There is an anisotropic behavior in relation to the study of the optical properties of these crystals along four directions of incidence of the electric field, where the anisotropy is more accentuated to the dihydrate. The studies fit in the theme of the role of Instituto de NanoBioEstruturas & Simulação NanoBioMolecular [NANO(BIO)SIMES], one of the National Institutes of Science and Technology funded by CNPq from the beginning of 2009, which aims to develop research activities and high-quality human resource training in nanobiostructures and nanobiomolecular simulation. / Com a finalidade do desenvolvimento de novos nanodispositivos, há um grande interesse em conhecer as propriedades eletrônicas de materias nanoestruturados. Sobretudo, como modificar as propriedades eletrônicas de nanoestruturas já bem conhecidas de forma controlada. Com este objetivo, muitas metodologias e experimentos tem sido desenvolvidos. Neste trabalho, estudamos de forma inteiramente atomística através de simulação computacional as propriedades eletrônicas, ópticas e vibracionais de (a) pontos quânticos esferéricos maciços e ocos de silício, (b) nanoflocos de grafeno e (c) cristais de ácido úrico anidro, mono e dihidratado utilizando métodos de Dinâmia Molecular, Semiempírico, DFTB+ e DFT, para tanto utilizamos o programa AMPAC e os módulos do Materials Studio (Accelrys), o Forcite, CASTEP, Gulp e o Dmol3 que são estados de arte em simulações atomísticas. Do ponto de vista clássico utilizamos campos de força Brenner, que permite a formação e rompimento de ligações covalentes; do ponto de vista quântico, utilizamos o método do funcional da densidade e DFTB+ . No estudo dos pontos quânticos silício obteve-se uma diminuição do gap de energia em função do aumento do raio para os pontos maciços, e comportamento contrário para os pontos ocos, quando fixamos um ponto e variamos tão somente o raio do buraco. Para os nanoflocos de grafeno obteve-se por meio de Dinâmica Molecular a estabilidade das estruturas, averiguando que até 1000K elas conservam sua forma plana; acima de 3400K as estruturas começam a ter suas ligações rompidas. Os gaps de energia HOMO-LUMO são sensíveis às bordas. A análise dos estados de spins revelou que somente os nanoflocos triangulares com borda zigzag possuem excesso de elétrons com spin alfa, dependente no entanto da simetria. Os modos de vibração para estruturas com nC ~ 50 foram obtidas e observou-se que nanofloco retangular exibe bandas de abosorção em comum com nanoflocos zigzag em dois intervalos do espectro infravermelho. Finalmente para os cristais de ácido úrico, observou-se que os parâmetros de rede para o cristal dihidratado são menos coerentes com valores experiemntais. O gap do cristal de ácido úrico anidro e mono é direto (~ 3.18 eV e 3.16 eV, respectivamente) e do dihidratado é indireto (~ 2.89 eV). Os orbitais 2p são os maiores contribuintes à densidade de estados. A água tem bastante influência na banda de condução do cristal dihidratado. Há um comportamento anisotrópico quando do estudo das propriedades ópticas destes cristais ao longo de quatro direções de incidência do campo elétrico, sendo a anisotropia mais acentuada para o dihidratado. As pesquisas realizadas enquadram-se na temática de atuação do Instituto de NanoBioEstruturas & Simulaçãoao NanoBioMolecular [NANO(BIO)SIMES], um dos Institutos Nacionais de Ciência e Tecnologia financiados pelo CNPq a partir do início de 2009, que visa desenvolver atividades de pesquisa e formação de recursos humanos de alto nível em nanobioestruturas e simulação nanobiomolecular.

Orientadores: Marilda Mazzali, José Butori Lopes de Faria / Tese ( doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T18:16:39Z (GMT). No. of bitstreams: 1 Mazali_FernandaCristina_D.pdf: 2274720 bytes, checksum: ce2fe44ee92ab230ab3a6648462a850b (MD5) Previous issue date: 2011 / Resumo: A nefrotoxicidade por ciclosporina caracteriza-se, do ponto de vista histológico, por fibrose intersticial em faixa, atrofia tubular e hialinose de arteríolas aferentes glomerulares, ou seja, um quadro compatível com doença renal isquêmica. Esta isquemia provocada pela ciclosporina leva a redução da taxa de filtração glomerular, com consequente elevação dos níveis séricos de ácido úrico. Além disto, a ciclosporina altera o transporte tubular de urato, favorecendo o desenvolvimento de hiperuricemia. No modelo experimental de nefropatia pela ciclosporina, a elevação dos níveis de ácido úrico apresenta associação com lesão túbulo intersticial mais severa, além de maior frequência de hialinose de arteríola aferente. Em estudos anteriores demonstramos que a hiperuricemia agrava a nefrotoxicidade pela ciclosporina e também que, a administração concomitante de agentes hipouricemiantes previne a lesão renal pela CsA. Assim, consideramos a hipótese de que, em um modelo experimental de nefropatia crônica pela ciclosporina, instalada, a normalização dos níveis de ácido úrico com alopurinol ou benzbromarona poderia reverter a lesão renal estabelecida. Nefropatia pela ciclosporina foi induzida em ratos Sprague Dawley com injeções subcutâneas diárias de ciclosporina, em associação com dieta hipossódica, por 5 semanas. Ao final deste período, grupos experimentais foram divididos com interrupção da ciclosporina, tratamento com CsA isolada ou em associação com alopurinol ou benzbromarona por um período adicional de 4 semanas. Ao final de 9 semanas de estudo, foram realizadas avaliações funcionais e histológicas. Neste modelo, a co-administração de alopurinol ou benzbromarona cursou com redução dos níveis de ácido úrico e minimizou o quadro de nefrotoxicidade estabelecida por ciclosporina, através da redução de hialinose arteriolar, glomeruloesclerose e fibrose intersticial, além da melhora da função renal, do estresse oxidativo e da apoptose, porém sem efeito anti inflamatório, avaliado pelo infiltrado de macrófagos e pela expressão de osteopontina. Os resultados mais significativos no grupo tratado com alopurinol sugerem que, além do efeito hipouricemiante, o alopurinol pode também apresentar um mecanismo antioxidante, conforme demonstrado pela redução da peroxidação lipídica e da geração de radicais livres, resultando em menor intensidade de apoptose de células tubulares renais. Assim, a redução dos níveis de ácido úrico neste modelo atuou como protetor na progressão da lesão de microvasculatura e na redução da área de fibrose intersticial, mas não da lesão inflamatória. No modelo de nefropatia pela ciclosporina, assim como no de hiperuricemia, ocorre elevação da atividade de renina, sugerindo a participação do sistema renina angiotensina aldosterona na fibrose renal. Para determinar este efeito, um segundo estudo utilizou a associação de um inibidor de enzima conversora da angiotensina (enalapril), um bloqueador de receptor AT1 de angiotensina (losartan) ou um inibidor competitivo da aldosterona (espironolactona) ao tratamento com ciclosporina, após a instalação da lesão. Os animais experimentais receberam ciclosporina por 5 semanas, e após a instalação da nefropatia, foram divididos em um dos grupos experimentais e acompanhados por um período adicional de 4 semanas. A utilização de moduladores do SRAA também cursou com melhora funcional e histológica da nefropatia pela ciclosporina, sem alteração dos marcadores de inflamação intersticial. A melhora da vasculopatia pode ser atribuída à redução do remodelamento vascular com estas drogas, porém com efeito limitado sobre a geração de radicais livres de oxigênio e apoptose de células tubulares. Em resumo, os resultados do presente estudo indicam que em modelo experimental de nefrotoxicidade por CsA, o uso de hipouricemiantes ou de modeladores do sistema-renina-angiotensina-aldosterona apresentaram um importante efeito renoprotetor, comparável, do ponto de vista funcional, à interrupção do tratamento com ciclosporina. As duas abordagens terapêuticas foram eficientes na limitação da progressão da nefropatia, com reversão parcial da fibrose intersticial, provavelmente mediada por melhora de oxigenação tecidual secundária à redução da vasculopatia e do remodelamento vascular. A manutenção do estímulo tóxico da ciclosporina, com manutenção da inflamação, da geração de radicais livres de O2 e da apoptose de células tubulares, entretanto, não foi completamente neutralizado pela intervenção farmacológica / Abstract: Chronic allograft nephropathy is characterized by stripped tubular atrophy and interstitial fibrosis, in presence of arteriolar hyalinosis, resembling an ischemic pattern of chronic kidney disease. Chronic ischemia is associated with reduced glomerular filtration rate, and increase in serum uric acid levels. Cyclosporine per se also has a direct effect on tubular urate handling that facilitates the development of hyperuricemia. Hyperuricemia exacerbates chronic cyclosporine nephropathy, with a more severe tubulointerstitial fibrosis and atrophy, as well as worsening of arteriolar hyalinosis. In a previous study we have shown that concomitant treatment with uric acid lowering agents limits the development of experimental CsA nephropathy. The hypothesis of the present study was that treatment with uric acid lowering agents, after the development of CsA nephropathy could reverse or reduce the severity of tubulointerstitial disease. Male Sprague Dawley rats received daily SC injections of cyclosporine in presence of low salt diet, during 5 weeks. At the end of this period, experimental groups were assigned for CsA withdrawal, maintenance of daily CsA alone or associated with allopurinol or benzbromarone in drinking water for an additional period of 4 weeks. At the end of 9 weeks of study, rats were sacrificed for functional and morphological analysis of kidneys. In this model, concomitant treatment with allopurinol or benzbromaroes was associated with reduction of serum uric acid levels, improvement in renal function and renal disease, characterized by lower arteriolar hyalinosis index, less glomerulosclerosis and significant reduction in interstitial fibrosis area. Other findings included reduction in oxidative stress markers and apoptotic cells, despite of maintenance of inflammatory status, quantified by macrophage infiltration and osteopontin expression. Allopurinol treatment was associated with more significant changes, with reduction of free radical generation, and lower grade of apoptotic cells in renal cortex, suggesting a participation of antioxidant effects in association with uric acid reduction. Taken together, these datsa suggests that reduction of serum uric acid in the stablished model of CsA nephropathy has a protective effect in microvascular lesions and progression of interstitial disease, despite the maintenance of interstitial inflammation. In cyclosporine nephropathy, as well as in the experimental hyperuricemia model, renal disease is associated with increased renin activity, suggesting the participation of renin angiotensin aldosterone system (RAS) in the mechanism of disease. In order to analyze the effect of RAS in CsA nephropathy model, a second study tested the treatment with angiotensin converting enzyme inhibitor (enalapril), a angiotensin II AT1 receptor blocker (losartan) or an aldosterone inhibitor (espironolactone) in association with cyclosporine after the development of chronic nephropathy. Experimental animals were treated with cyclosporine and low salt diet for 5 weeks, and then assigned for one treatment group, including cyclosporine withdrawal, cyclosporine alone, CsA and enalapril, CsA and losartan or CsA and espironolactone for an additional period of 4 weeks. RAS blockade in the established model of CsA nephropathy was associated with improvement in renal function and interstitial fibrosis, despite the maintenance of interstitial inflammation. The most striking finding was the improvement of arteriolar hyalinosis and glomerulosclerosis, suggesting that the most important effect was protecting against vascular remodeling. The improvement in vasculopathy was associated with reduction in tissue hypoxia, with a partial reduction in oxidative stress and tubular cell apoptosis. Both therapeutic interventions proved to be efficient in limiting progression of renal disease, with a partial reversion of interstitial fibrosis. The main mechanism is associated with improvement in renal tissue O2 delivery, as a consequence of recovery of arteriolar hyalinosis and control of vascular remodeling. However, maintenance of CsA therapy was associated with a persistent toxic effect, with maintained interstitial inflammation, free radical generation and tubular cell apoptosis that was not neutralized by intervention / Doutorado / Ciencias Basicas / Doutor em Clínica Médica