Introdução: Várias evidências em estudos de animais knockout sugerem a efetiva participação dos genes Fgf9-Fgfr2 no processo de determinação testicular. Animais XY knockout para os genes Fgf9 e Fgfr2 apresentam reversão sexual como consequência da alteração na cascata de eventos masculinizantes nas gônadas fetais. Até o momento, mutações inativadoras dos genes FGF9-FGFR2 não foram descritas em pacientes 46, XY portadores de disgenesia gonadal. Objetivos: Pesquisar a presença de mutações inativadoras nos genes FGF9 e FGFR2 em pacientes portadores de DDS 46,XY por anormalidades do desenvolvimento gonadal. Casuística e Métodos: Trinta e três pacientes com disgenesia gonadal 46, XY, 11 com a forma completa e 22 com a forma parcial. As regiões codificadoras dos genes FGF9 e FGFR2 de todos os pacientes foram amplificadas e sequenciadas. As investigações quanto a presença de deleções foram realizadas usando-se a técnica de MLPA (Multiplex ligation-dependent probe amplification). Resultados: Mutações ou deleções nos genes FGF9 não foram encontradas em nenhum dos pacientes estudados, apenas alguns polimorfismos previamente descritos. No gene FGFR2 não foram encontradas deleções. Uma nova variante não sinônima em heterozigose, c.1358 C>T (p.Ser453Leu), localizada no exon 10 do FGFR2 foi encontrada em duas irmãs com disgenesia gonadal parcial 46,XY. A mãe é portadora da variante alélica e o estudo de 147 indivíduos controles não identificou a presença desta variante. A análise da variante em sites de previsão, PolyPhen, SIFT e Mutation Taster indicou que a nova proteína FGFR2 é possivelmente danificada. Conclusões: Se esses resultados dos sites de previsão forem confirmados em estudos funcionais futuros a participação do gene FGFR2 na determinação gonadal masculina em humanos estará comprovada / Introduction: Several evidence in animal studies \"knockout\" suggest the effective participation of Fgf9-Fgfr2 genes in testicular determination process. Animals XY \"knockout\" for Fgf9 and Fgfr2 genes exhibit sex reversal as a result of the change in the cascade of masculinizing events in fetal gonads. To date, So far inactivating mutations of FGF9 and FGFR2 genes have not been described in 46,XY patients with gonadal dysgenesis. Objectives: To investigate the presence of inactivating mutations in the FGF9 and FGFR2 gene in patients with 46,XY DSD by gonadal abnormalities. Casuistic and Methods: Thirty-three patients with 46,XY gonadal dysgenesis, 11 with the full form and 22 with the partial form. The coding regions of FGF9 and FGFR2 genes of all patients were amplified and sequenced. Investigations on the presence of deletions were made using the MLPA technique (\"Multiplex ligation-dependent probe amplification\"). Results: Mutations or deletions in the FGF9 gene were not found in any of the patients studied, only a few polymorphisms previously described. FGFR2 gene deletions were not found. A new non-synonymous variant in heterozygosis, c.1358 C> T (p.Ser453Leu) located in exon 10 of FGFR2 was found in two sisters with 46,XY partial gonadal dysgenesis. The mother is a carrier of the variant allele and the study of 147 control subjects did not identify the presence of this variant. The analysis of the variant on prediction sites, \"PolyPhen\", \"SIFT\" and \"Mutation Taster\" indicated that the new FGFR2 protein is possibly damaged. Conclusions: If the results of the prediction sites are confirmed by future functional studies the participation of the FGFR2 gene in human male gonadal determination will be proven

The progressively increasing prevalence of the Metabolic Syndrome (MetS) has emerged as a major global health concern since the MetS is associated with an increased risk for cardiovascular morbidity and mortality. Central obesity represents a key feature of the MetS and is strongly related to all MetS comorbidities. Dysregulation of adipose tissue-derived proteins, so called adipokines, has been implied to partially contribute to these effects. Recently, fibroblast growth factor-21 (FGF-21) has been introduced as a novel insulin sensitizing and weight reducing adipokine with potential therapeutic properties. However, data on FGF-21 elimination are rather limited. Therefore, FGF-21 regulation in relation to renal function has been investigated in a patient population with chronic kidney disease (CKD, study population 1), as well as one with acute kidney impairment (study population 2). In study population 1 (n = 499), patients were distributed into five CKD subgroups according to estimated glomerular filtration rate (eGFR). Median FGF-21 serum concentrations progressively increased from CKD stage 1 to stage 5 and highest values of FGF-21 were detected in stage 5 (1: 86.4 ng/l; 2: 206.4 ng/l; 3: 289.8 ng/l; 4: 591.3 ng/l; 5: 1918.1 ng/l). Furthermore, eGFR remained the strongest predictor for FGF-21 levels in multivariate analysis. For study population 2 (n = 32), blood samples were obtained before elective unilateral partial or total nephrectomy, as well as within 30 hours after surgery. In this population FGF-21 levels significantly increased after surgery (325.0 ng/l) as compared to before surgery (255.5 ng/l). Furthermore, relative changes of FGF-21 were independently and positively predicted by relative changes of creatinine in this cohort. These results are in accordance with the hypothesis that FGF-21 is eliminated by the kidneys and that the extent of kidney dysfunction substantially contributes to serum FGF-21 levels. However, additional animal experiments and prospective clinical studies are needed to further elucidate the role of the kidneys in FGF-21 physiology.

No description available.

<p>Human physiology is dependent on an accurate phosphate (Pi) homeostasis. Defective Pi regulation causes hyper- or hypophosphatemia, which are associated with ectopic calcification or impaired bone mineralization, and a shortened life span. Current endocrine models of Pi homeostasis are incomplete. However, studies of acquired and hereditary disorders of Pi homeostasis have revealed new potential Pi regulating hormones, Phosphatonin(s). One of these is fibroblast growth factor-23 (FGF23). FGF23 is produced in bone and is secreted into the circulation. Mutations in FGF23 causes disturbed Pi regulation, without the appropriate counter-regulatory actions of parathyroid hormone or vitamin D. By the generation of FGF23 transgenic mice, which display phenotypic similarities to patients with hypophosphatemic disorders, we show that FGF23 exerts endocrine actions in the kidney and causes osteomalacia. Renal FGF23 actions severely decrease Pi reabsorption and expression of Klotho, a suggested age suppressor gene, known to be crucial in FGF23 receptor binding and activation. In bone, our transgenic model displays impaired osteoclast polarization, which should be detrimental to osteoclastic bone resorption in osteomalacia. However, in our model osteoclasts efficiently participate in bone matrix degradation. Furthermore, we investigated a large population-based cohort in order to elucidate the role of FGF23 in normal physiology. Importantly, we were able to demonstrate an association of FGF23 to parathyroid hormone, renal function and bone mineral density and we found a correlation of FGF23 to weight and body fat mass. The studies on which this thesis is based, demonstrate that FGF23 has phosphatonin-like properties and that the skeleton functions as an endocrine organ. In addition, the results indicate that FGF23 has a role in bone mineral and lipid metabolism, and that FGF23 is a possible diagnostic marker and therapeutic target for the future.</p>

No description available.

La peau est un organe à l'architecture complexe qui assure plusieurs rôles essentiels dont celui de barrière contre les agressions extérieures. De plus, il est capable de se régénérer grâce un processus hautement régulé: la cicatrisation. Des biomatériaux, synthétisés à partir de macromolécules d'origine naturelle et/ou synthétique, ont été développés pour servir de pansements, de support de culture cutanée ou de substitut cutané.L'originalité de notre étude a été de mimer, non pas la matrice extracellulaire dermique, mais le réseau de fibrine, temporaire, qui apparait lors de la cicatrisation. Au cours de travaux précédents, il a été démontré qu'il était possible de renforcer mécaniquement un réseau de fibrine, à concentration physiologique, en l'associant, dans une architecture de réseaux interpénétrés de polymères (RIP), avec un réseau de polyoxyde d'éthylène (POE). Durant mes travaux, la non toxicité de ces matériaux envers des cellules modèles a été démontrée. Puis, la composition du matériau a été optimisée pour augmenter son module de stockage jusqu'à un facteur 100 par rapport à celui du gel de fibrine. Ensuite, grâce à la synthèse d'alcool polyvinylique méthacrylate (PVAm) pour le remplacement du POE, un matériau présentant mêmes qualités, mais plus facilement stockable à l'état déshydraté et complètement réhydratable, a pu être obtenu. Nous nous sommes ensuite attachés à rendre ce nouveau matériau biodégradable. L'introduction de sérum albumine bovine méthacrylate (BSAm) copolymérisée avec le PVAm (co-réseau) dans une architecture RIP avec un réseau de fibrine a permis de synthétiser un matériau hydride présentant l'ensemble des propriétés précédemment décrites et dégradable par des enzymes. Ce matériau a été testé en contact avec des populations cellulaires fibroblastiques. Il a pu être démontré, qu'en plus d'être non cytotoxique, ce matériau pouvait être totalement colonisé par ces cellules. Pour finir, l'encapsulation de cellules à l'intérieur de cette matrice et leur prolifération ont pu être observées. En conclusion, les matériaux synthétisés lors de ces travaux, c'est-à-dire des RIPs associant un réseau de fibrine à la concentration physiologique et un réseau de polymère synthétique, possèdent les propriétés nécessaires pour être utilisés en tant que pansements et supports de culture pour la régénération cutanée. De plus, la possibilité d'encapsuler des fibroblastes dans le RIP à base de coréseaux de PVAm et BSAm en fait un substitut cutané potentiel.Mots clefs : hydrogel, réseaux interpénétrés de polymères, fibrine, POE, PVA, BSA, encapsulation cellulaire, fibroblaste, médecine régénérative, peau. / The skin is an organ with a complex architecture that provides several key roles including barrier against external aggressions. In addition, it has the ability to regenerate itself by following a highly regulated process,: the wound healing. Biomaterials, synthesized by using macromolecules from natural and/or synthetic origin, have been developed to serve as wound dressing, cell culture support or skin substitute.The originality of our study was to not mimic the dermal extracellular matrix, but mimic the the fibrin scaffold, the temporary matrix who appears during the healing process. In previous work, it was shown that it was possible to mechanically reinforce a fibrin scaffold at physiological concentration by associating into interpenetrating polymer network (IPN) architecture with a polyethylene oxide (PEO) network. In my work, the non-toxicity of these materials was proved with model cells. Then, the material composition has been optimized to increase the storage modulus by 100 in comparison of the fibrin scaffold. Then, through the synthesis of polyvinyl alcohol methacrylate (PVAm) to replace the POE, a material with the same properties, but more easily stored in a dehydrated state (more ductile) and completely rehydratable could be obtained. We then attached to make this new biodegradable material. The use of bovin serum albumin methacrylate (BSAm) copolymerized with PVAm(conetwork) into IPN architecture with a fibrin scaffold performs to synthesize a hybrid material with all the properties described above and degradable by enzymes. This material has been tested in contact with human fibroblast. It has been demonstrated that in addition to be non-cytotoxic, this material could be completely colonized by these cells. Finally, the encapsulation of cells in the bulk of this matrix and their proliferation inside were observed.In conclusion, the materials synthesized in this work, IPN containing a fibrin scaffold at physiological concentration and a synthetic polymer network, have sufficient properties to be used as wound dressings or cells culture support for skin regeneration. In addition, the ability to encapsulate fibroblasts in material based on conetwork of PVAm and BSAM makes it suitable for a skin substitute application.Key words: hydrogel, Interpenetrating Polymer Network, fibrin, POE, PVA, BSA, entrapping, fibroblast, tissue engineering, skin.

Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...

Evidências sugerem que o fator de crescimento de fibroblasto 2 (FGF2), produzido por melanomas, possui importante papel no crescimento tumoral, angiogênese e metástase. Assim, o uso de anticorpo monoclonal (mAb) que reconhece e bloqueia a atividade de FGF2 é uma abordagem a ser considerada em oncologia. O propósito desse estudo foi avaliar a aplicação diagnóstica e terapêutica de um novo anticorpo anti-FGF2, 3F12E7 IgG1, em melanoma experimental B16-F10. Para isso, camundongos C57Bl/6 foram implantados subcutaneamente (ou intravenosamente, para ensaios de metástase) com células de melanoma murino B16-F10 (5x105 células/animal). Quando tumores alcançaram 3-4 mm de diâmetro (ou 24 h pós-inóculo de células B16-F10, no caso de ensaios de metástase), camundongos foram tratados com anti-FGF2 3F12E7 IgG. Animais controle receberam igual volume do veículo ou quantidade de anticorpo controle de isotipo. Grupos: animais tratados com (1) anti-FGF2 3F12E7 IgG1; (2) ligante de CEA IgG1 (controle de isotipo); e (3) veículo. O tratamento dos camundongos portadores de tumor com anti-FGF2 IgG resultou, comparado com os controles salina e de isotipo, em uma redução no número de focos metastáticos nos pulmões (ANOVA, p < 0,05), em ensaios de metástase experimental, bem como em uma menor taxa de crescimento de tumores subcutâneos (n=7/grupo). Esse resultado é acompanhado por uma redução na densidade vascular do tumor, conforme determinado por imunomarcação para CD34 ou CD31. A captação tumoral de anti-FGF2 3F12E7 IgG foi avaliada por métodos de medicina nuclear, usando esse anticorpo radiomarcado com tecnécio-99m. Estudos SPECT/CT in vivo e de biodistribuição ex vivo revelaram que 99mTc-anti-FGF2 3F12E7 IgG pode atingir eficientemente tumores subcutâneos e metastáticos de B16-F10. Assim, esses dados sugerem que anti-FGF2 3F12E7 IgG pode ser uma estratégia antitumoral promissora para melanoma, bem como uma potencial ferramenta de imagem a ser explorada, atuando como um possível traçador para rastrear tumores FGF2-positivos e mapear esse estímulo angiogênico no microambiente tumoral. Aprovado pelo comitê de ética (CAPPesq): número 0942/09 / Compelling evidence suggests that fibroblast growth factor 2 (FGF2), produced by melanomas, plays important role in tumor growth, angiogenesis and metastasis. Therefore, the use of a monoclonal antibody (mAb) that recognizes and blocks FGF2 activity is seen as an approach to be considered in oncology. The purpose of this study was to evaluate the diagnostic and therapeutic application of a new anti-FGF2 antibody, 3F12E7 IgG1, in experimental melanoma B16-F10. For this, C57Bl/6 mice were subcutaneously (or intravenously, for experimental metastasis assay) implanted with murine melanoma B16-F10 cells (5x105 cells/animal). When tumors reached 3-4 mm in diameter (or 24 h after B16-F10 cells injection, in the case of metastasis assay), mice started receiving anti-FGF2 3F12E7 IgG. Control mice received equal volume of vehicle or isotype control IgG amount. Groups: (1) anti-FGF2 3F12E7 IgG1-treated, (2) CEA-binding IgG1-treated (isotype control) and (3) vehicle-treated mice. The treatment of tumor-bearing mice with anti-FGF2 IgG, compared with saline and isotype controls, led to a reduction in the number of metastatic foci in the lungs (ANOVA test, p < 0.05), in experimental metastasis assays, as well as to a lower subcutaneous tumor growth rate (n=7 per group). This result is accompanied by a reduction in the tumor vascular density, as determined by CD34 or CD31 staining. The anti-FGF2 3F12E7 IgG tumor uptake was evaluated by nuclear medicine approaches, using this antibody radiolabeled with technetium-99m. In vivo SPECT/CT and ex vivo biodistribution studies reveled that 99mTc-anti-FGF2 IgG could efficiently achieved B16-F10 subcutaneous and metastatic tumors. Thus, these data suggest that the anti-FGF2 3F12E7 IgG may be a promising antitumor strategy for melanoma, as well as a potential imaging tool to be explored, working as a possible tracer to identify FGF2-positive tumors and map this angiogenic stimulus in the tumor microenvironment. Ethics committee (CAPPesq) approval number 0942/09

Ein in der chirurgischen Implantologie nicht gelöstes Problem ist die mangelhafte Versiegelung von Implantaten, die Haut und Weichgewebe penetrieren, sogenannte Hautdurchleitungen. Infolgedessen kommt es hier zu rezidivierenden oder chronischen periimplantären Entzündungen. Ziel der Studie war es, ein in-vitro Modell zu entwickeln, mit dem es möglich ist, die Adhäsion und Proliferation von Fibroblasten an unterschiedlich oberflächen- veränderten Titanwerkstoffen zu untersuchen. Verwendet wurden polierte, sand- und glaskugelgestrahlte, Kollagen-A- und Silikon- beschichtete Titanplättchen. Die Hälfte dieser Plättchen wurde noch zusätzlich mit dem Radio-Frequency-Glow-Discharge-Verfahren (RFGDT) physikalisch vorbe- handelt. Somit ergaben sich insgesamt 10 Oberflächenmodifikationen. Die ober- flächenveränderten Titanplättchen wurden in Wells einer 96er Mikrotiterplatte ein- gebracht. Anschließend wurden die Wells mit Nährstofflösung aufgefüllt und mit 1 x 104 Fibroblasten (humane Fibroblasten) beschickt. Der Kultivierungszeitraum zur Austestung der Zelladhäsion betrug 12 Stunden, für die Proliferation 72 Stunden. Nach Ablösen der Fibroblasten von den Titanträgern erfolgte die Zellzählung in der Neubauer-Zählkammer. Die quantitativ gewonnenen Ergebnisse wurden mathematisch-statistisch aufgearbeitet. Parallel zu jedem Versuchsdurchgang wurde der Zellbewuchs auf jeweils zwei Titanplättchen pro Oberflächenart rasterelektronenmikroskopisch qualitativ analysiert und deskriptiv-statistisch anhand eines eigens entwickelten Scores (Werte 1 - 7) ausgewertet. Das RFGD-Verfahren erwies sich bezüglich der Adhäsion bei sand- und kugelgestrahlten sowie bei Kollagen-A-bschichteten Trägern den physikalisch unbehandelten überlegen. Für polierte Titanträger ließ sich keine Aussage treffen, bei Silikon-beschichteten Trägern war das RFGDT von Nachteil. Fibroblasten adhärierten am besten an polierten, physikalisch unbehandelten Titanwerkstoffen. An Silikon-beschichteten Trägern kam es zur geringsten Fibroblastenanhaftung. Bezüglich des Gesamteffektes von Adhäsion und Proliferation, also nach 72-stündiger Zellkultivierung, ergab sich eine deutliche Überlegenheit der polierten und Kollagen-A-beschichteten Oberflächen, die physikalisch mit dem RFGD-Verfahren vorbehandelt waren. Auch hier wiesen die Silikon-beschichteten Träger den geringsten Fibroblastenbewuchs auf. Überdies erwies sich, dass eine schlechtere Adhäsion durch verbesserte Proliferation der Fibroblasten wett gemacht werden kann und vice versa. In der REM ließ sich an den polierten Titanplättchen eine nahezu perfekte Anpassung der Fibroblasten an die Werkstoffoberflächen nachweisen. Mit Hilfe der qualitativen rasterelektronenmikroskopischen Befunde lässt sich jedoch nur das zu erwartende Ausmaß der Zelladhäsion prognostizieren. Hinsichtlich der Fibroblastenproliferation kommt es zwischen qualitativ und quantitativ ermittelten Resultaten zu teilweise deutlichen Unterschieden. Der Vergleich der gewonnenen Resultate mit den Ergebnissen einer Studie der Keratinozytenadhäsion und -proliferation an identischen Werkstoffoberflächen zeigt, dass beide Zellspezies, Fibroblasten und Keratinozyten, gleichermaßen den besten Bewuchs an Kollagen-A-dotierten und physikalisch vorbehandelten Oberflächen aufweisen. Während jedoch Fibroblasten an polierten Titanwerkstoffen das beste Adhäsions- und Proliferationsverhalten zeigen, kommt es an diesen Oberflächen zum geringsten Keratinozytenbewuchs. Andererseits zeigen Fibroblasten an Silikon- beschichteten Werkstoffen das signifikant schlechteste Wachstum, wohingegen Silikon-beschichtete gegenüber sandgestrahlten Titanoberflächen für Keratinozyten von Vorteil sind. Zwecks Überprüfung der in vitro gewonnenen Resultate ist eine Versuchsreihe mit Kollagen-A-beschichteten Titanwerkstoffen am lebenden Organismus erforderlich. Es ist nicht auszuschließen, dass es in vivo aufgrund der Komplexität und Variabilität an Einflussgrößen noch zu deutlichen Abweichungen von den in vitro ermittelten Ergebnissen kommen kann. Zudem fallen die hier gewählten Kultivierungszeiträume beim lebenden Organismus in die Periode der Entzündungsphase, welche der Implantation eines Biomaterials folgt. Auch die hier vorgestellte Studie belegt, dass das Design eines idealen Implantats für jede Zellpopulation, mit welcher der Werkstoff in Berührung kommt, eine spezifische Oberflächentextur erfordert. / An unsolved problem in surgical implantology is the inadequately sealed junction between transcutaneous implants and surrounding skin or soft tissue. This results in reoccurring or chronic peri-implantary inflammation. The purpose of this study was to develop an in-vitro model enabling the examination of adhesion and proliferation of fibroblasts on surface variations of titanium materials. The surfaces employed in this study were polished, sandblasted, glassblasted, collagen-A and silicon coated titanium platelets. Additionally, half of these platelets had been preprocessed with radio frequency glow discharge treatment (RFGDT). Thus, in total ten surface modifications have been involved. Platelets were deposited in wells of a 96 micro-titre plate. Then these wells were filled with nutritive solution and loaded with 1 x 104 fibroblasts (human fibroblasts). Cultivation period was 12 hours for testing cell adhesion and 72 hours for testing proliferation. After being detached from the titanium carrier cells were counted in a Neubauer counting chamber. The quantitative results were subjected to mathematical-statistical appraisal. In parallel to each test procedure cell growth on two titanium platelets per surface modification was subjected to quantitative analysis on an electron microscopic grid and to descriptive-statistical evaluation with a custom-developed scoring system (values 1-7). The RFGD process gave improved adhesion results on sandblasted and glassblasted as well as on collagen-A coated surfaces. For silicon coated carriers RFGDT showed a negative influence were as no significant results could be achieved for polished titanium carriers. Best fibroblast adhesion was observed on polished, physically untreated titanium materials, poorest adhesion was determined on silicon-coated material. The combined effect of adhesion and proliferation observed after 72 hour cell cultivation was obviously superior in the polished and collagen A coated surfaces which had been pretreated with RFGD. Silicon coated surfaces exhibited the lowest fibroblast growth. Poorer adhesion can be compensated by improved fibroblast proliferation and vice versa. Almost perfect adaptation of fibroblasts to material surface was exhibited by REM on polished titanium platelets. The findings established in the electron microscopic grid can predict only the expected extent of cell adhesion. In some cases there is a significant difference between results of fibroblast proliferation determined qualitatively on one hand and quantitatively on the other. A comparison of the results gained in this work with those of a study of adhesion and proliferation of keratinocytes on identical surfaces shows that both cell species, fibroblasts as well as keratinocytes, demonstrate the best growth on collagen-A loaded, physically pre-treated surfaces. Whereas fibroblasts show the best adhesive and proliferative behaviour on polished titanium materials, keratinocytes feature the lowest growth. Conversely, fibroblasts grow poorest on silicon coated surfaces, whereas keratinocytes favour silicon coated materials over sandblasted titanium surfaces. In order to monitor the results gained in vitro, an in vivo test series with collagen-A- loaded titanium materials would be appropriate. It cannot be excluded that an in vivo study might generate significant deviations from results established in vitro because of the complex and variable nature of parameters. In addition, cultivation periods chosen in this study, transpire in the living organism during the inflammation phase following implantation of a biomaterial. Further studies are required to comprehend the epithelial and connective tissue organisation process in the implant environment. The study presented here verifies that the design for ideal implant requires a specific surface for each cell population with which the material comes into contact.

INTRODUÇÃO: O paratormônio (PTH) e o fator de crescimento de fibroblastos 23 (FGF-23) aumentam precocemente durante o curso da doença renal crônica (DRC) antes do desenvolvimento de hiperfosfatemia. Este estudo avaliou os efeitos de dois quelantes de fósforo, acetato de cálcio (Ca) e hidrocloreto de sevelamer (SEV), nos níveis de PTH e FGF-23 de pacientes com DRC. MÉTODOS: Quarenta e dois pacientes com DRC estágios III e IV foram randomizados em 2 grupos para receber durante 6 semanas, Ca ou Sev. Após este período os pacientes foram seguidos por mais 2 semanas (washout). Analisamos os efeitos destes quelantes sobre os parâmetros do metabolismo ósseo e mineral. RESULTADOS: No início do estudo, os pacientes apresentaram-se com fração de excreção do fósforo, PTH e FGF-23 séricos elevados. Durante o tratamento com quelantes de fósforo houve um declínio progressivo nos níveis de PTH e fósforo urinário, mas sem mudanças nos níveis séricos de cálcio e fósforo. Ocorreu uma mudança significativa nos níveis de FGF-23 no grupo de pacientes tratados com Sev. CONCLUSÕES: Este estudo confirmou os efeitos positivos da prescrição de quelantes de fósforo no controle do PTH, nos estágios III e IV da DRC. Estudos prospectivos e de longo seguimento são necessários para confirmar os efeitos do Sev sobre os níveis de FGF-23 e os benefícios de sua redução sobre parâmetros como mortalidade / INTRODUCTION: Parathyroid hormone (PTH) and fibroblast growth factor (FGF-23) levels increase early in CKD before the occurrence of hyperphosphatemia. This study evaluated the effect of two phosphate binders, calcium carbonate or sevelamer hydrocloride, on PTH and FGF-23 levels in patients with CKD. METHODS: Forty two patients were randomized in two groups to receive calcium acetate or sevelamer hydrochloride, over a 6-wk period. After that, the patients were followed by more two weeks and effects of phosphate binders on mineral parameters were analyzed. RESULTS: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH and FGF-23 During treatment with both phosphate binders, there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF-23 only in sevelamer-treated patients. CONCLUSIONS: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer hydrocloride on serum FGF-23 and the benefits of this decrease on outcomes