PREMESSA: Le linee guida raccomandano la fistola AV radio-cefalica autogena (RCAVF)come prima scelta per l'emodialisi. Preoccupazione è stata sollevata che questo potrebbe non essere appropriato nei pazienti anziani. METODO: Noi abbiamo seguito in modo prospettico 126 pazienti per tre anni. Dopo sistematica valutazione clinica ed ecografica, la RCAVF è stata creata utilizzando un microscopio operatore. La pervietà è stata valutata subito, a 1 settimana, a 1 mese e a 1 anno. I risultati sono stati registrati e stratificati in 2 gruppi: <70a e > 70a. RISULTATI: La RCAVF è stata creata nel 75% dei <70a e nel 70% dei >70a. L'incidenza di insuccesso immediato è stata 11% (<70a) e 13% (>70a). La pervietà primaria e secondaria ad 1 anno è stata 67% e 84% (<70a), 63% e 80% (>70a). CONCLUSIONI: La microchirurgia ha permesso la creazione di RCVAF in >70a con un rischio accettabile di fallimento e lievi differenze rispetto a <70a. L'età non deve precludere una creazione di RCAVF. / BACKGROUNDS: Guidelines recommend autogenous radial-cephalic AV fistula (RCAVF) as the first-choice for haemodialysis. Concern has been raised that this may not be appropriate in the elderly. We evaluated the results of microsurgery for RCAVF creation in elderly patients. METHODS: We prospectively followed 126 patients during three years. After systematic clinical and ultrasound evaluation, a RCAVF was created using a surgical microscope. Patency was assessed immediately, at 1 week, 1 month and 1 year. The outcomes were recorded and stratified into 2 groups: <70y and >70y. RESULTS: RCAVF was created in 75% of <70y and 70% of >70y. Incidence of early failure was 11% (<70y) and 13% (>70y). Primary and secondary patency at 1 year was 67% and 84% (<70y), 63% and 80 %(>70y) . CONCLUSIONS: Microsurgery allowed the creation of RCAVF in >70y with acceptable risk of failure and slight differences by comparison with <70y. Older age should not preclude an RCAVF creation.

Introduzione. Recenti studi hanno dimostrato che il Rituximab (RTX) è un’alternativa sicura ed efficace alla ciclofosfamide nell’indurre la remissione in pazienti con severa vasculite ANCA-associata (AAV) di nuova diagnosi o recidiva. Scopo dello studio era valutare l’efficacia e la sicurezza del RTX nei nostri pazienti con AAV. Metodi. Studio retrospettivo delle caratteristiche cliniche, dei risultati e della tolleranza al RTX dei pazienti con AAV trattati presso il nostro centro da Gennaio 2006 a Dicembre 2011. Inizialmente veniva utilizzato lo schema convenzionale delle 4 somministrazioni settimanali da 375 mg/m2. Dal 2011 sulla base dell’esperienza maturata e dei nuovi dati della letteratura si decideva di non adottare uno schema fisso per le recidive, ma di somministrare una o due dosi secondo la severità della recidiva ed il rischio infettivo. Risultati. Venivano trattati 51 pazienti con AAV, 15/51 (29%) di nuova diagnosi e 36/51 (71%) ad una recidiva. La maggior parte dei pazienti con nuova diagnosi presentavano una micropoliangioite con severo interessamento renale, 5/15 (33%) erano in dialisi dall’esordio. 32/36 (89%) pazienti trattati ad una recidiva presentavano una recidiva granulomatosa di Granulomatosi di Wegener (WG). Tutti ottenevano una remissione, più rapidamente per le manifestazioni vasculitiche. 2/5 pazienti in dialisi dall’esordio recuperavano la funzione renale. Si osservavano 11 recidive in 9 pazienti con GW mediamente dopo 23.1 mesi, tutti ottenevano nuovamente la remissione. Ad un follow-up medio di 20.1 mesi si registravano 4 decessi, 3 (3/15, 20%) nel gruppo di pazienti con nuova diagnosi, uno (1/36, 3%) nel gruppo trattato ad una recidiva. Quattro pazienti sospendevano il RTX per infezioni. Conclusioni. Nella nostra casistica il RTX si è dimostrato efficace e sicuro nell’indurre la remissione in pazienti con severa AAV, sia all’esordio che alla recidiva. I pazienti con WG presentano maggior rischio di recidiva e dovrebbero pertanto essere mantenuti in terapia immunosoppressiva dopo RTX. / Background. Recently Rituximab (RTX) has proved to be an effective and safe alternative to Cyclophosphamide for remission induction in newly diagnosed and relapsing anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to evaluate the efficacy and safety of RTX in our cohort of AAV-patients. Method. A retrospective study of the main clinical characteristic, outcomes, and RTX tolerance of AAV patients treated in our centre from January 2006 to December 2011. Initially we adopted the conventional schedule of RTX administration (4 weekly doses of 375 mg/m2). Since 2011, basing on our previous experience and new literature data, we have decided to not use a fixed schedule to treat relapse but to administer 1 or 2 doses of RTX according to individual AAV severity and infective risk. Results. Fifty-one AAV-patients were treated, 15/51 (29%) with newly diagnosed AAV and 36/51 (71%) with relapsing AAV. The majority of newly diagnosed patients had microscopic polyangiitis (9/15, 60%) with severe renal involvement, 5/15 (33%) were on dialysis at diagnosis. 32/36 (89%) patients treated for relapse had Wegener’s Granulomatosis (WG) with granulomatous relapses. All patients achieved clinical remission, within 4-6 weeks for vasculitic manifestation, it took longer for granulomatous manifestation. 2/5 patients on dialysis recovered renal function. Eleven relapses were observed in 9 patients with WG after 23.1 months on average, which were successfully re-treated with RTX. At an average follow-up of 20.1 months four deaths were observed, 3 (3/15, 20%) in the newly diagnosed patients and one (1/36, 3%) in patients treated for relapse. Four patients stopped RTX for infection. Conclusion. In our cohort RTX was found to be safe and effective for remission induction of newly diagnosed and relapsing AAV-patients. WG has an increased risk of relapse and therefore after RTX patients with WG should be maintained with immunosuppressive therapy.

L'insufficienza renale cronica (CKD) è associata ad un rischio cardiovascolare più elevato rispetto alla popolazione generale: fattori come uremia, stress ossidativo, età dialitica, infiammazione, alterazioni del metabolismo minerale e presenza di calcificazioni vascolari incidono fortemente sulla morbosità e mortalità per cause cardiovascolari nel paziente uremico. Diversi studi hanno verificato il coinvolgimento dei progenitori endoteliali (EPC) nella malattia aterosclerotica ed è stato dimostrato che esprimono osteocalcina, marcatore di calcificazione. Inoltre, nella CKD è presente una disfunzione in numero e funzionalità delle EPC. Attualmente, il ruolo delle EPC nella formazione delle calcificazioni vascolari nei pazienti in dialisi non è stato ancora chiarito. Lo scopo della tesi è quello di studiare le EPC prelevate da pazienti con CKD, al fine di determinarne numero e fenotipo. È stato anche valutato l'effetto del trattamento in vitro e in vivo con calcitriolo e paracalcitolo sulle EPC, dato il deficit di vitamina D dei pazienti con CKD: il trattamento con vitamina D sembra avere effetti positivi sul sistema cardiovascolare. Sono stati valutati: numero di EPC circolanti e la relativa espressione di osteocalcina e del recettore della vitamina D; morfologia e fenotipo EPC in vitro; effetti di calcitriolo e paracalcitolo sull’espressione di osteocalcina e sui depositi di calcio. I risultati dello studio suggeriscono che il trattamento con vitamina D abbia un effetto positivo sulle EPC, aumentando il numero di EPC circolanti e normalizzandone la morfologia. Sia calcitriolo che paracalcitolo sono in grado di ridurre notevolmente l’espressione di OC, mentre solo il paracalcitolo ha un effetto significativo sulla riduzione dei depositi di calcio in coltura. In conclusione, il trattamento con vitamina D sembra ridurre il potenziale calcifico delle EPC nell’uremia, aprendo nuove strade per la gestione del rischio cardiovascolare nei pazienti affetti da CKD. / Chronic Kidney Disease (CKD) is associated to an increased cardiovascular risk compared to the general population: factors like uremia, oxidative stress, dialytic vintage, inflammation, mineral metabolism dysregulation and vascular calcifications greatly affect cardiovascular morbidity and mortality in CKD. Several papers reported the involvement of endothelial progenitor cells (EPCs) in atherosclerosis: it was also demonstrated their expression of osteocalcin, a marker of calcification. Moreover, a dysfunction in number and functionality of EPCs is also detectable in CKD. Currently, the role of EPCs in the pathogenesis of vascular calcifications in patients with CKD is not clear. The project presented herein aimed to study EPCs from CKD patients and determine their number and phenotype. Moreover, it was evaluated the effect of treatment with calcitriol and paricalcitol on EPCs, both in vivo and in vitro, because CKD patients suffer from vitamin D deficiency and it was reported that vitamin D has beneficial effects on the cardiovascular system. The number of circulating EPCs and their expression of osteocalcin and vitamin D receptor, morphology and phenotype of EPC in vitro, effects of calcitriol and paricalcitol on expression of osteocalcin and calcium deposition where evaluated. The results suggest that treatment with vitamin D has beneficial effects on EPCs, by increasing their number and improving morphology. Both calcitriol and paricalcitol could strongly reduce the expression of osteocalcin by EPCs, whereas only paricalcitol was able to reduce the deposition of calcium in cell cultures. In conclusion, treatment of CKD patients with vitamin D seems to reduce the calcific potential of EPCs in uremia, highlighting a putative protective role of vitamin D therapy against vascular calcifications.

Background. Hhereditary cystic kidney diseases are a heterogeneous spectrum of disorders leading to renal failure. Clinical features and family history can help to distinguish the recessive from dominant diseases but the differential diagnosis is difficult due the phenotypic overlap. The molecular diagnosis is often the only way to characterize the different forms. A conventional molecular screening is suitable for small genes but is expensive and time-consuming for large size genes. Next Generation Sequencing (NGS) technologies enables massively parallel sequencing of nucleic acid fragments. Purpose. The first purpose was to validate a diagnostic algorithm useful to drive the genetic screening. The second aim was to validate a NGS protocol of PKHD1 gene. Methods. DNAs from 50 patients were submitted to conventional screening of NPHP1, NPHP5, UMOD, REN and HNF1B genes. 5 patients with known mutations in PKHD1 were submitted to NGS to validate the new method and a not genotyped proband with his parents were analyzed for a diagnostic application. Results. The conventional molecular screening detected 8 mutations: 1) the novel p.E48K of REN in a patient with cystic nephropathy, hyperuricemia, hyperkalemia and anemia; 2) p.R489X of NPHP5 in a patient with Senior Loken Syndrome; 3) pR295C of HNF1B in a patient with renal failure and diabetes.; 4) the NPHP1 deletion in 3 patients with medullar cysts; 5) the HNF1B deletion in a patient with medullar cysts and renal hypoplasia and in a diabetic patient with liver disease. The NGS of PKHD1 detected all known mutations and two additional variants during the validation. The diagnostic NGS analysis identified the patient’s compound heterozygosity with a maternal frameshift mutation and a paternal missense mutation besides a not transmitted paternal missense mutation. Conclusions. The results confirm the validity of our diagnostic algorithm and suggest the possibility to introduce this NGS protocol to clinical practice.

There is an urgent need to improve the performance of urine cytology for the diagnosis of bladder cancer. In preliminary studies, telomerase activity evaluated by telomeric repeat amplification protocol (TRAP) assay and chromosomal aneuploidy detected by fluorescence in situ hybridization (FISH) in the diagnosis of bladder cancer have produced important results. Urine cell-free (UCF) DNA has also been proposed as a potential marker for early bladder cancer diagnosis. In the first study the diagnostic performance of TRAP assay and FISH analysis was assessed, while the second study evaluated the potential role of UCF DNA integrity in early bladder cancer diagnosis. In the first cross-sectional study, 289 consecutive patients who presented with urinary symptoms underwent cystoscopy and cytology evaluation. In the second study, UCF DNA was isolated from 51 bladder cancer patients, 46 symptomatic patients, and 32 healthy volunteers. c-Myc, BCAS1 and HER2 gene sequences longer than 250 bp were quantified by real time PCR to verify UCF DNA integrity. In the first study, sensitivity and specificity were 0.39 and 0.83, respectively, for cytology; 0.66 and 0.72 for TRAP; 0.78 and 0.60 for the cytology and TRAP combination; 0.78 and 0.78 for the cytology, TRAP and FISH combination; and 0.65 and 0.93 for the TRAP and FISH combination. In the second study, at the best cutoff of 0.1 ng/µl, UCF DNA integrity analysis showed a sensitivity of 0.73 and a specificity of 0.84 in healthy individuals and 0.83 in symptomatic patients. The preliminary results suggest that these biomarkers could potentially be used for the early diagnosis of bladder cancer, especially in high-risk populations (e.g, symptomatic individuals exposed to occupational risk) who may benefit from the use of noninvasive diagnostic tests in terms of cost-benefit.

I pazienti con glomerulopatie con sindrome nefrosica hanno poche opzioni di trattamento efficace. Riportiamo la nostra esperienza sull'utilizzo della fotochemioterapia extracorporea ( ECP) in 9 pazienti in cui non era stata osservata una risposta efficace/duratura alla convenzionale terapia farmacologica. L’ECP è una promettente terapia immunomodulante, che è stata utilizzata con successo nel trattamento di altre condizioni immunomediate come il rigetto nel trapianto e il GvHD. METODI: In questo studio abbiamo arruolato 9 pazienti, 5 maschi e 4 femmine, età media 32.7±8.9 anni, affetti da sindrome nefrosica e non responsivi/resistenti alle comuni terapie. Il follow-up medio è stato di 41.3±21.7 mesi. Tutti i pazienti sono stati sottoposti a cicli di fotochemioterapia extracorporea secondo il seguente schema: 1ciclo (2 sedute in 2 giorni consecutivi) ogni 15 giorni per tre mesi, seguito da 1ciclo al mese per tre mesi. Il follow up è stato effetuatio ogni 3 mesi durante il primo anno e poi ogni 12 mesi. Durante il follow up sono stati monitorati pressione arteriosa, funzione renale, marcatori diretti ed indiretti di attività della malattia e indici di flogosi. RISULTATI: attraverso l'analisi dei parametri ematochimici indici di attività di malattia, e monitorando l'eventuale progressione della malattia renale, è stato possibile dimostrare che l' ECP può rappresentare per casi selezionati di pazienti una valida ulteriore opzione terapeutica. Secondo i risultati preliminari tale trattamento risulta inoltre caratterizzato da un eccellente profilo di sicurezza . CONCLUSIONI: I risultati osservati suggeriscono che l’ECP è un trattamento efficace per i pazienti con glomenulonefriti con sindrome nefrosica, soprattutto in coloro che presentano ancora una buona funzionalità renale. Valutazioni cliniche aggiuntive dovranno aiuteranno a definire meglio la popolazione di pazienti in cui ECP sia più efficace e raccomandabile. / Patients with glomerulopathies associated with nephrotic syndrome have few effective treatment options. Here we report on the use of extracorporeal photochemotherapy (ECP) in 9 patients in whom glomerulopathy failed to respond to pharmacologic therapy. ECP is a promising immunomodulatory therapy associated with few side effects, that has been successfully used in the treatment of other immune-mediated conditions such as solid organ transplant rejection and graft-versus-host disease. METHODS: In this study, we enrolled 9 patients, 5 males and 4 females, mean age 32.7±8.9 years, suffering from nephrotic syndrome. The mean follow-up was 41.3±21.7 months. All patients were subjected to cycles of extracorporeal photochemotherapy according to the following scheme: 1 cycle (2 sessions on 2 consecutive days) every 15 days for three months, followed by 1 cycle per month for three months. The follow-up was performed every 3 months during the first year and then every 12 months. during follow-up were monitored blood pressure, renal function, indirect markers of disease activity and phlogosis indexes. RESULTS: through the analysis of blood chemistry parameters markers of disease activity, and by monitoring eventual progression of chronic kidney disease, it has been possible to show that the ECP may represent for selected cases of patients a viable additional option. This treatment also would be, according to preliminary results, characterized by an excellent safety profile. CONCLUSIONS: The results suggest that ECP is a feasible treatment for patients with glomerulopathies associated with nephrotic syndrome who have adequate baseline renal function. Additional clinical evaluation will have to be performed to better define the patient population in which ECP is most effective.

Made available in DSpace on 2013-08-07T19:05:35Z (GMT). No. of bitstreams: 1 000449287-Texto+Completo-0.pdf: 1220722 bytes, checksum: 847130381b149aae03742c54c7df7199 (MD5) Previous issue date: 2013 / Background : Kidney transplantation is recognized as the best form of treatment for patients needing renal replacement therapy, significantly improving the quality of life of patients and reducing mortality rates. It is known that the HLA compatibility improves the outcome of transplantations. In Rio Grande do Sul until 2001 transplant based on HLA compatibility between donor and recipient, but the results of this policy change are not yet known in the researched. Objective : Knowing the results in the researched of kidney transplants from deceased donors performed with HLA compatibility distribution as well as the association of these findings with other risk factors for graft loss and patient death. Method : A historical cohort study in a single center, involving 315 patients transplanted with kidneys from deceased donors. We evaluated the results of transplants occurred from May 2001 to May 2011 through the curves and overall survival by HLA compatibility and graft patient in 5 years, as well as analyzed the risk factors for graft loss and patient death. For survival curves, we used the Kaplan-Meier method and comparisons between them were made with the log rank test. For univariate and multivariate analysis of risk factors associated with the outcomes we used the method of Cox Regression. Results : 5-year overall survival of the graft was 69. 8% and the patient was 82. 1%. In this study could not demonstrate that HLA compatibility was a risk factor for graft loss or patient death. In multivariate analysis only recipient age was associated with death (HR 1. 033 / p = 0. 023) and graft loss was related to vascular and endocrine complicactions (HR 2. 388 / p = 0. 001 and HR 0. 283 / p = 0. 014, respectively).Conclusion : The results showed a graft survival and patient satisfaction in five years is comparable to that observed internationally. To demonstrate that the HLA can be related to graft survival and patient will need a larger sample. Vascular and endocrine complications have shown association with graft survival and recipient age was related to patient survival. / Introdução : Sabe-se que a compatibilidade HLA melhora de forma geral os resultados dos transplantes. No Rio Grande do Sul a partir de 2001 iniciou-se a transplantar baseado em compatibilidade HLA entre doador e receptor, mas os resultados desta mudança de política ainda não são conhecidos no meio pesquisado. Objetivo : Conhecer os resultados, no meio pesquisado, dos transplantes de rins provenientes de doadores falecidos feitos com distribuição conforme compatibilidade HLA, bem como a associação destes resultados com os outros fatores de risco para perda do enxerto e óbito do paciente.Método : Estudo de coorte histórica, em um único centro, envolvendo 315 pacientes transplantados com rins provenientes de doadores falecidos. Foram avaliados os resultados dos transplantes ocorridos de maio de 2001 a maio de 2011 através das curvas das sobrevidas global e por compatibilidade HLA do enxerto e do paciente em 5 anos, assim como foram analisados os fatores de risco para perda de enxerto e óbito do paciente. Para as curvas de sobrevida foi utilizado o método de Kaplan-Meier e as comparações entre elas foram realizadas com o teste Log Rank. Para as análises uni e multivariadas dos fatores de risco associados aos desfechos foi utilizado o método de Regressão de Cox. Resultados : Em 5 anos a sobrevida global do enxerto foi de 69,8% e do paciente foi de 82,1%. No meio estudado não foi possível demonstrar que a compatibilidade HLA foi um fator de risco para perda do enxerto ou óbito do paciente. Nas análises multivariadas apenas a idade do receptor mostrou-se associada ao óbito (HR 1,033/p=0,023) e a perda de enxerto foi relacionada às complicações vasculares e endócrinas (HR 2,388/p=0,001 e HR 0,283/p=0,014, respectivamente).Conclusão : Os resultados demonstraram uma sobrevida do enxerto e do paciente em 5 anos satisfatória sendo comparável ao observado internacionalmente. Para demonstrar que a compatibilidade HLA possa ter relação com a sobrevida do enxerto e do paciente será necessário uma amostra maior. As complicações vasculares e endócrinas mostraram ter associação com a sobrevida do enxerto e a idade do receptor mostrou-se relacionada à sobrevida do paciente.

Controvérsias existem sobre os benefícios da hemodiálise de alto fluxo e alta eficiência em relação a hemodiálise convencional. Este estudo compara, através de parâmetros clínicos, laboratoriais, avaliação do sistema nervoso periférico e autônomo, os pacientes em hemodiálise convencional(HDC) e, após, em hemodiálise de alto fluxo e alta eficiência(HDAF), usando os mesmos parâmetros da cinética da uréia, por um período de tempo de 4-8 meses em cada modalidade de tratamento hemodialitico. O sistema nervoso periférico foi avaliado através da miografia e da neurografia de membros superiores e inferiores. O estudo da variabilidade da freqüência cardíaca, através de seis índices no domínio do tempo, foi usado para avaliar o sistema nervoso autônomo nestes pacientes. Não houve diferença quanto às manifestações intradialíticas nos dois tipos de hemodiálise e nem alteração dos níveis tensionais no período de acompanhamento. Na avaliação laboratorial, verificou-se diferença estatisticamente significativa entre a HDC e HDAF nos seguintes parâmetros: creatinina(9,6mg/dl±2,3x10,9mg/dl±2,0;p<0,01),reserva alcalina (16,5mEq/l±2,5x18,2mEq/l±2,7; p<0,05), ácido úrico(6,3mg/dl±1,3x7,1mg/dl±1,64;p<0,01), fósforo(6,4mg/dl±1,3x7,2mg/dl ±1,4;p<0,01) e albumina(4,1mg/ml±0,5x3,8mg/ml±0,27;p<0,01). Observou-se melhora significativa da velocidade de condução sensitiva do nervo ulnar na HDAF(40,72m/s±5,11x48,01m/s±7,7;p<0,05). Houve redução significativa da variabilidade da freqüência cardíaca nos pacientes urêmicos em hemodiálise, comparativamente ao grupo de indivíduos normais. Concluiu-se que não houve diferença significativa nos parâmetros clínicos entre os dois tipos de hemodiálise. Observou-se redução significativa da albumina na HDAF, bem como aumento significativo da creatinina, reserva alcalina, fósforo e ácido úrico. Houve melhora significativa da velocidade de condução sensitiva do nervo ulnar nos pacientes em HDAF. Os pacientes em hemodiálise apresentam deterioração significativa do Sistema Nervoso Autônomo comparativamente ao grupo controle.

SOUSA, Fabíola Carine Monteiro de. Efeito renal do veneno da Bothrops erythomelas e bloqueio induzido pelo fator antibotrópico do Dedelphis marsupialis. 2004. 128 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2004. / Submitted by denise santos (denise.santos@ufc.br) on 2012-03-22T16:10:34Z No. of bitstreams: 1 2004_dis_fcmsousa.pdf: 1396935 bytes, checksum: 05b7233fbbba81191027570385fec567 (MD5) / Approved for entry into archive by Eliene Nascimento(elienegvn@hotmail.com) on 2012-03-26T11:51:35Z (GMT) No. of bitstreams: 1 2004_dis_fcmsousa.pdf: 1396935 bytes, checksum: 05b7233fbbba81191027570385fec567 (MD5) / Made available in DSpace on 2012-03-26T11:51:35Z (GMT). No. of bitstreams: 1 2004_dis_fcmsousa.pdf: 1396935 bytes, checksum: 05b7233fbbba81191027570385fec567 (MD5) Previous issue date: 2004 / Some animals present natural resistance to the effects of snake venoms that can be explained by the presence of neutralizing factors in their blood serum. The resistance of South American Didelphis marsupialis, against crotalid venoms, especially of the genus Bothrops, of utmost medical importance in Brazil, has been object of investigation in the last few years. Bothrops erythromelas, known as “jararaca-da-seca” or “jararaca-malha-de-cascavel” is responsible for a great deal of snakebites in Northeastern Brazil. The venom of this snake induces acute renal failure (Wen et al., 1989). In this work, we examined the action of the antibothropic factor isolated from Didelphis marsupialis on the renal effects of B. erythromelas venom in the absence of systemic interactions. Isolated kidneys from Wistar rats, weighing 260 to 300g, were perfused with Krebs-Henseleit solution containing 6g% of bovine serum albumin, Bothrops erythromelas venom (10mg/mL), antibothropic factor from Didelphis marsupialis (10mg/mL), antibothropic factor from Didelphis marsupialis (10mg/mL) incubated with Bothrops erythromelas venom (10mg/mL) and antibothropic factor from Didelphis marsupialis (30mg/mL) incubated with Bothrops erythromelas venom (10mg/mL). The parameters studied included perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), percent sodium, potassium and chloride tubular transport (%TNa+, %TK+ and %TCl-), and osmotic clearance (Cosm). The control group perfused with albumin was functionally stable for over 120 min. The administration of antibothropic factor from Didephis marsupialis (10µg/mL) did not modify the functional kidney parameters when compared with control group. The infusion of B. erythromelas venom (10µg/mL) caused a significant decrease (p< 0,05*) in perfusion pressure and renal vascular resistance at 60, 90 and 120 min. with maximum effect at 90 min. (PP→ ct90 = 108.70 ± 5.1 mmHg vs vBE90 = 65.20 ± 5.6* mmHg) and (RVR→ ct90 = 5.76 ± 0.65 mmHg/mL.g-1.min-1. vs vBE90 = 3.10 ± 0.45* mmHg/mL.g-1.min-1). The glomerular filtration rate decreased at 60 min. and increased at 90 and 120 min (ct120 = 0.72 ± 0.10 mL.g-1.min-1. vs vBE120 = 1.24 ± 0.26* mL.g-1.min-1). After administration of the venom, the urinary flow increased at 90 and 120 min when compared with control group (ct120 = 0.14 ± 0.07 mL.g-1.min-1. vs vBE120 = 0.47 ± 0.08* mL.g-1.min-1). Sodium transport percent decreased at 90 and 120 min. (ct90 = 79.18 ± 0.88% vs vBE90 = 58.35 ± 4.86* %). Potassium transport percent decreased at 90 and 120 min. (ct90 = 67.20 ± 4.04% vs vBE90 = 57.32 ± 5.28* %). Chloride transport percent decreased at 60, 90 and 120 min. (ct90 = 77.32 ± 2.22% vs vBE90 = 55.97 ± 5.52* %). The osmotic clearance increased at 90 and 120 min. (ct120 = 0.13 ± 0.01 mL. g-1.min-1 vs vBE120 = 0.42 ± 0.07* mL.g-1.min-1). The antibothropic factor from Didelphis marsupialis (10µg/mL) incubated with B. erythromelas venom (10µg/mL) blocked only the effects promoted by venom in the perfusion pressure and in the renal vascular resistance, whereas the highest concentration of the antibothropic factor from Didelphis marsupialis (30µg/mL) reversed the effects on renal vascular resistance, urinary flow, glomerular filtration rate, percent sodium potassium and chloride tubular transport (%TNa+, %TK+ and %TCl-), and osmotic clearance (Cosm). In conclusion, B. erythromelas venom altered all the renal functional parameters evaluated and the antibothropic factor from D.marsupialis was able to inhibit the effects induced by the venom in rat isolated kidney.

JORGE, Antonio Rafael Coelho. Interações entre a ingestão alta de sódio e os peptídeos urodilatina e uroguanilina na função renal de ratos. 2013. 117 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013. / Submitted by denise santos (denise.santos@ufc.br) on 2016-03-23T12:29:22Z No. of bitstreams: 1 2013_tese_arcjorge.pdf: 2340659 bytes, checksum: 811458e18b30f0f794b4356e4f09d389 (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2016-03-23T13:13:26Z (GMT) No. of bitstreams: 1 2013_tese_arcjorge.pdf: 2340659 bytes, checksum: 811458e18b30f0f794b4356e4f09d389 (MD5) / Made available in DSpace on 2016-03-23T13:13:26Z (GMT). No. of bitstreams: 1 2013_tese_arcjorge.pdf: 2340659 bytes, checksum: 811458e18b30f0f794b4356e4f09d389 (MD5) Previous issue date: 2013 / The high sodium intake in the diet has increased considerably in recent decades, promoting the development of several chronic diseases such as hypertension, stroke and coronary heart disea se. Peptides such as urodilatin (UD) and uroguanylin (UGN) have been implicated in the regulation of salt and water homeostasis. However, the regulatory mechanisms are not well understood, as well as their interactions on ren al function. The aim of this work is to study the main effects of the peptides UD and UGN in kidneys of rats subjected to high NaCl intake. The effects were examined using rats for 10 days kept in metabolic cages. The control group received distilled water only, whereas the treated group received 2% solution of NaCl. Kidney function was assessed by perfusion of the isolated rat kidney. Data were compared using Student's t test and ANOVA with significance level of 5%. The UD promoted reduction of perfusion p ressure, renal vascular resistance and urine flow was also observed increased excretion of sodium and chloride, with changes most prominent at the distal level. However, after treatment with salt UD effects were not seen, there was an increase in transport of sodium and chloride to the proximal most pronounced. The effects of UGN were also evaluated in the presence of salt, which was observed to increase perfusion pressure, urine flow and glomerular filtration rate, followed by an increase in the excretion of sodium and chloride, especially at the proximal tubule. The results also showed increased expression of mRNA GC - C receptor and a slight reduction in the expression of GC - A in rats treated with salt. After an increased intake of salt, physiological pathw ays are activated well regulated in order to eliminate excess sodium. The UGN seems to be the primary hormone involved in this pathway, but the UD also have interests in this process. The GC - C receptor is directly involved in the regulation of these physio logical processe. / O elevado consumo de sódio na dieta tem aumentado consideravelmente nas últimas décadas, promovendo o desenvolvimento de diversas doenças crônicas, como hipertensão arterial, acidente vascular cerebral e doenças coronarianas. Peptídeos como a urodilatina (UD) e uroguanilina (UGN) têm sido implicados na regulação da homeostase de sal e água. Porém, os mecanismos de regulação ainda não foram bem esclarecidos, assim como suas interações na função renal. O objetivo desse trabalho é estudar os principais efeitos dos peptídeos UD e UGN em rins de ratos submetidos a alta ingestão de NaCl. Os efeitos foram examinados usando ratos Wistar mantidos por 10 dias em gaiolas metabólicas. O grupo controle recebeu somente água destilada, enquanto que o grupo tratado recebeu 2% de solução de NaCl. A função renal foi avaliada através da perfusão de rim isolado de ratos. Os dados foram comparados através de teste t de Student e ANOVA, com significância de 5%. A UD promoveu redução da pressão de perfusão, resistência vascular renal e fluxo urinário, foi observado também aumento da excreção de sódio e cloreto, sendo as alterações mais proeminentes ao nível distal. Contudo, após tratamento com sal os efeitos da UD não foram vistos, observou-se um aumento transporte de sódio e cloreto mais pronunciado ao nível proximal. Os efeitos da UGN também foram avaliados na presença do sal, onde foram observados a elevação da pressão de perfusão, fluxo urinário e ritmo de filtração glomerular; seguido de aumento na excreção de sódio e cloreto, principalmente ao nível de túbulo proximal. Os resultados também demonstraram a expressão aumentada de mRNA do receptor GC-C e uma discreta redução na expressão de GC-A em ratos tratados com sal. Após uma ingestão aumentada de sal, são ativadas vias fisiológicas muito bem reguladas no objetivo de eliminar o excesso de sódio. A UGN parece ser o hormônio primordial envolvido nessa via, contudo a UD apresentam também participações nesse processo. O receptor GC-C está diretamente envolvido na regulação desses processos fisiológicos