Made available in DSpace on 2019-03-29T23:50:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-06-06 / Background - Acute kidney injury (AKI) is an independent risk factor for mortality in adults and children. In 2007 the RIFLE criteria (Risk, Injury, Failure, Loss and End Stage classification) were adapted for the pediatric population (pRIFLE score), which facilitated the studies on this entity in the pediatric population. Generally, urine output (UO) < 1 mL/kg/h is accepted as oliguria in neonates, although it has not been systematically studied. pRIFLE criteria suggest UO cut-offs similar to those of the adult population (0.3 and 0.5 mL/kg/h). The aim of the present study was to investigate UO in correlation with mortality in critically ill neonates and suggest changes in the pRIFLE definition of reduced diuresis. Methods - A retrospective cohort study was performed in an eight-bed neonatal intensive care unit (NICU). UO was systematically measured by diaper weight each 3 h. Discriminatory capacity to predict mortality of UO was measured and patients were divided according to UO ranges:G1 > 1.5 mL/kg/h; G2 1.0 1.5 mL/kg/h; G3 0.7 1.0 mL/kg/h and G4 < 0.7 mL/kg/h. These ranges were incorporated to pRIFLEGFR criteria and its performance was evaluated. Results - Of 384 patients admitted at the NICU during the study period, 72 were excluded and overall mortality was 12.8%. UO showed good performance for mortality prediction (area under the curve 0.789, P < 0.001). There was a stepwise increase in hospital mortality according to UO groups after controlling for SNAPPE-II and diuretic use. Using these UO ranges with pRIFLE improves its discriminatory capacity (area under the receiver operating characteristic curve 0.882 versus 0.693, P< 0.05). Conclusions - UO is a predictor of mortality in NICU. An association between a UO threshold < 1.5 mL/kg/h and mortality was observed, which is higher than the previously published pRIFLE thresholds. Adopting higher values of UO in pRIFLE criteria can improve its capacity to detect AKI severity in neonates. / Introdução - A lesão renal aguda (LRA) é um fator de risco independente para mortalidade em adultos e crianças. Em 2007, a classificação RIFLE para LRA (classificação Risk, Injury, Failure, Loss and End Stage) foi adaptada para a população pediátrica (pRIFLE), o que facilitou os estudos sobre essa entidade na população. Geralmente, o débito urinário (DU) < 1,0 ml/kg/h é aceito como oligúria em neonatos, embora esse valor não tenha sido sistematicamente estudado. A classificação pRIFLE sugere pontos de corte na diurese similares aos utilizados em adultos (0,3 e 0,5 ml/kg/h). O objetivo desse presente estudo foi investigar a correlação do DU com mortalidade em recém-nascidos criticamente enfermos e avaliar se os valores utilizados no pRIFLE para o débito urinário são adequados para o uso na população neonatal. Metodologia - Foi realizado um estudo de coorte retrospectivo em uma unidade de terapia intensiva neonatal (UTIN) de oito leitos. O DU foi sistematicamente medido através do peso das fraldas a cada três horas. A capacidade discriminatória do DU para predizer mortalidade foi avaliada e os pacientes foram divididos de acordo com faixas de DU: G1 > 1,5 ml/kg/h; G2 1,0 - 1,5 ml/kg /h; G3 0,7 1,0 ml/kg/h e G4 < 0,7 ml/kg/h. Essas faixas foram incorporadas ao critério pRIFLE (TFG) e seu desempenho foi avaliado. Resultados - Dos 384 pacientes admitidos na UTI durante o período do estudo, 72 foram excluídos e a mortalidade geral foi de 12,8%. O DU mostrou um bom desempenho preditora de mortalidade (área sobre a curva ROC (AuROC) 0, 789, P < 0,001). Houve um aumento gradual da mortalidade hospitalar de acordo com os grupos de diurese após ajuste para SNAPPE-II e uso de diuréticos. Utilizando essas faixas de diurese com o pRIFLE, houve uma melhora na sua capacidade discriminatória (AUROC 0,882 versus 0,693, p <0,05). Conclusão - O DU é um preditor de mortalidade em UTIN. Uma associação entre DU < 1,5 ml/kg/h e mortalidade foi observado, sendo maior do que o publicado previamente com o pRIFLE. Adotar valores mais elevados para o DU no critério pRIFLE pode melhorar sua capacidade de detectar a gravidade da LRA em recém-nascidos.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-03-27T13:35:23Z No. of bitstreams: 2 Dissertação - Emmeline Flor Ribeiro - 2014.pdf: 1787776 bytes, checksum: c8a4106ef03ff49855997007460d4558 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-03-27T14:47:39Z (GMT) No. of bitstreams: 2 Dissertação - Emmeline Flor Ribeiro - 2014.pdf: 1787776 bytes, checksum: c8a4106ef03ff49855997007460d4558 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-03-27T14:47:39Z (GMT). No. of bitstreams: 2 Dissertação - Emmeline Flor Ribeiro - 2014.pdf: 1787776 bytes, checksum: c8a4106ef03ff49855997007460d4558 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-12-09 / Aspidosperma subincanum Mart. is a medicinal herb used for the treatment of hypercholesterolemia, diabetes and digestive illnesses. The bitter tonic of its bark is known by the indigenous population to stimulate circulatory functions. Although a previous study showed that EEAS induces hypotension associated with bradycardia and vasodilation, no scientific data have been described to evaluate the diuretic effects of this Brazilian medicine plant. The aim of the present study was to evaluate the diuretic activity of an ethanol extract of Aspidosperma subincanum (EEAS), and possible mechanisms of action, using Wistar rats. EEAS, 60, 120 and 300 mg/Kg, or furosemide (20 mg/Kg) were orally administered and the rats were kept individually in metabolic cages for 24h for urine collection 1, 2, 4, 6, 8, 12 and 24h after treatments. To evaluate the involvement of prostanoids in the diuretic action of EEAS, the animals received piroxicam (5 mg/Kg, i.p.), a nonselective inhibitor of cyclooxygenase, before treatment with EEAS 120 mg/Kg. The control groups received only saline (NaCl, 0,9%), or saline and piroxicam. The urinary volume, the water consumption, electrolyte excretion and pH were measured. The oral administration of EEAS 60 and 120mg/Kg increased significantly the urine and electrolyte excretion of Na+ and K+ continuously throughout the study period, wherein increased the urinary output from the first hour after treatment, and increased the electrolytes from the second hour onwards after treatment. EEAS 60 and 120 mg/Kg caused a relative increase in cumulative diuresis around of 77% and 142,95%, respectively, compared with the control group. EEAS 300 mg/Kg increased the urinary excretion from 8 h after treatment. From 4 h until the end of the experiment, the group treated with EEAS 120 mg/kg provided a major excretion of Na+ than the furosemide group, while the group treated with EEAS 60 mg/Kg provided a similar excretion of Na+ when compared to the group that received furosemide. The furosemide group showed significantly higher amounts of K+ in the urine when compared with the others group. The urinary excretion of EEAS was reduced by piroxicam 2 h, 4 h and 8 h after treatments by around 54.2%, 50.3% and 38.9%, respectively. Piroxicam reduced Na+ excretion between 4 and 8 h after treatments by 38.4 and 39.0%, respectively. And still inhibited the K+ excretion by around 28.2% at 4 h and 47.1% at 8 h. The results suggest that EEAS could present compound(s) responsible for diuretic activities, and the mechanism could involve prostanoids system. / O Aspidosperma subincanum Mart. é uma planta medicinal conhecida popularmente por ser utilizada no tratamento de hipercolesterolemia, diabetes e doenças digestivas. O tônico amargo de sua casca é conhecido pela população indígena por estimular as funções circulatórias. Embora, um estudo prévio tenha demonstrado que o extrato etanólico de Aspidosperma subincanum (EEAS) induz hipotensão associada à bradicardia e vasodilatação, nenhum estudo científico avaliou os efeitos diuréticos dessa planta medicinal brasileira. O objetivo do presente estudo foi avaliar a atividade diurética do EEAS e possíveis mecanismos de ação, utilizando ratos Wistar. EEAS, 60, 120 e 300 mg/Kg, ou furosemida (20 mg/Kg) foram administrados, via oral, e os ratos foram colocados individualmente em gaiolas semi-metabólicas durante 24 h para a coleta de urina, nos períodos de 1, 2, 4, 6, 8, 12 e 24 h após os tratamentos. Para avaliar o envolvimento da via dos prostanoides no possível efeito diurético do EEAS, os animais receberam piroxicam (5 mg/Kg, i.p.), um inibidor não seletivo das cicloxigenases, previamente ao tratamento com EEAS 120 mg/Kg. Os grupos controle receberam apenas salina (NaCl, 0,9%), ou salina e piroxicam. O volume urinário, o consumo de água, a excreção de eletrólitos e o pH foram medidos. A administração oral de EEAS 60 e 120 mg/Kg aumentou significativamente a excreção urinária e de eletrólitos Na+ e K+ durante o período de estudo, sendo que houve aumento do volume urinário a partir da primeira hora após os tratamentos, e aumento da excreção de eletrólitos a partir de 2 h após os tratamentos. EEAS 60 e 120 mg/Kg causaram aumento relativo na diurese cumulativa de 24 h em aproximadamente 77% e 142,95%, respectivamente, comparado com grupo controle. EEAS 300 mg/Kg causou aumento da excreção urinária a partir de 8 h após tratamento. De 4 h até o final do experimento, o grupo tratado com EEAS 120 mg/kg proporcionou maior excreção de Na+ do que o grupo tratado com furosemida, enquanto o grupo tratado com EEAS 60 mg/Kg proporcionou excreção similar ao grupo furosemida, sendo que neste grupo ocorreu maior excreção de K+ na urina quando comparado com os outros grupos. A excreção urinária do EEAS foi reduzida por piroxicam nos períodos de 2 h, 4 h e 8 h após os tratamentos na proporção de 54.2%, 50.3% e 38.9%, respectivamente. O piroxicam também inibiu a excreção de Na+ entre 4 e 8 h após os tratamentos, na proporção de 38.4 e 39.0%, respectivamente. Ainda inibiu excreção de K+ na ordem de 28.2% em 4 h e 47.1% em 8 h. Os resultados mostram que o EEAS apresenta compostos ativos responsáveis pela atividade diurética em ratos, e o mecanismo de ação parece envolver a via dos prostanoides.

Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-05-21T13:44:05Z No. of bitstreams: 1 Disserta??o Rosirene DallAgnese p?s-banca.pdf: 1579820 bytes, checksum: 8b18b2dd28fd5e5160df51c8f463aef9 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-06-06T17:55:06Z (GMT) No. of bitstreams: 1 Disserta??o Rosirene DallAgnese p?s-banca.pdf: 1579820 bytes, checksum: 8b18b2dd28fd5e5160df51c8f463aef9 (MD5) / Made available in DSpace on 2018-06-06T17:58:54Z (GMT). No. of bitstreams: 1 Disserta??o Rosirene DallAgnese p?s-banca.pdf: 1579820 bytes, checksum: 8b18b2dd28fd5e5160df51c8f463aef9 (MD5) Previous issue date: 2017-10-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: Respiratory diseases in pediatrics are important causes of hospitalization in the Pediatric Intensive Care Unit (PICU) and, not withstanding, to the need for mechanical ventilation. The use of mechanical ventilation and continuous sedation associated with the administration of fluids, which severe patients need for initial hemodynamic stabilization, often result in a cumulative positive fluid balance. This hydric overload is associated with worse outcomes. Among the alternatives for the hydric balance to be optimized, the establishment of the prone position is found as such. Objectives: To verify if the prone position in pediatric patients submitted to mechanical ventilation increases diuresis with optimization in the hydric balance as well as to verify if this improvement has repercussions in days of mechanical ventilation and hospitalization in PICUs. Methods: Retrospective cohort through review of medical records. It was selected patients who were submitted to ventilation for pulmonary causes and aged from 1 month old to 12 years old. The prone group (PG) was the one in which the patients were submitted to the prone position at some point of the study. The control group (CG) was the one in which the patients met the inclusion criteria but were not undergone prone position. The collected data included demographic data, Pediatric Index of Mortality (PIM 2), hydric balance, diuresis, use of diuretics and vasoactive drug index, mechanical ventilation duration, prone position duration, relationship between prone and mechanical ventilation duration, besides duration of hospital stay (PICU and hospital). Mann-Whitney and Chi-Square tests were used to compare the PG and CG groups. For the longitudinal analysis, repeated measures of ANOVA were used, using BH (ml/kg/day), diuresis (ml/kg/h) and the amount of furosemide (mg/kg/day) during a period classified as D1 to D4 (D1 being the first day of mechanical ventilation in the CG and the day immediately before prone in the PG). The main outcome was the increase of diuresis and the improvement of hydric balance in pronated patients. The secondary outcome was the decrease of duration of mechanical ventilation and hospitalization in the PICU and in the hospital. Results: 84 patients were included and, after some losses, 77 (PG=37 and CG=40) remained. Regarding age, sex, pathologies, index of mortality, death, use of vasoactive drugs and occurrence of intercurrences, the groups were similar. There was no significant improvement of diuresis, hydric balance, mechanical ventilation and hospitalization duration in the PICU. Regarding the use of diuretics, there was greater use of furosemide (P<0.001) and spironolactone (P=0.04) in the PG. When performed a longitudinal analysis of repeated measures of D1 to D4, it was shown that both PG and CG had improved diuresis and hydric balance, with a more significant improvement from D1 to D2 in the PG (P=0.034). However, when verifying this improvement, it was noticed that it was also related to the use of diuretics. Conclusion: Throughout the analysed days of mechanical ventilation (D1 to D4), there was improvement of both diuresis and hydric balance of patients in both groups, without showing, however, superiority of the prone group in relation to the control group. / Introdu??o: Doen?as respirat?rias em pediatria s?o importantes causas de interna??o em Unidade de Terapia Intensiva Pedi?trica (UTIP) e, n?o raro, levam a necessidade de ventila??o mec?nica. O uso de ventila??o mec?nica e de seda??o cont?nua associados ? administra??o de fluidos que o paciente grave necessita para a sua estabiliza??o hemodin?mica inicial, frequentemente ocasionam balan?o h?drico positivo cumulativo. Essa sobrecarga h?drica est? associada a piores desfechos. Entre as alternativas para que o balan?o h?drico seja otimizado, encontra-se, entre outras, a instaura??o da posi??o prona. Objetivos: Verificar se a posi??o prona em pacientes pedi?tricos submetidos a ventila??o mec?nica aumenta a diurese com otimiza??o no balan?o h?drico, bem como aferir se essa melhora repercute em dias de ventila??o mec?nica e de interna??o em UTIP. M?todos: coorte retrospectiva atrav?s de revis?o de prontu?rios. Foram selecionados os pacientes, submetidos a ventila??o por causa pulmonar, com idade entre 1 m?s e 12 anos. O grupo prona (GP) foi aquele em que os pacientes foram submetidos a posi??o prona em algum momento do estudo. O grupo controle (GC) foi aquele em que os pacientes preencheram os crit?rios de inclus?o, mas que n?o foram submetidos a posi??o prona. Os dados coletados inclu?ram dados demogr?ficos, escore de mortalidade (PIM 2), balan?o h?drico, diurese, uso de diur?ticos e ?ndice de drogas vasoativas, tempo de ventila??o mec?nica, tempo de posi??o prona, rela??o entre o tempo de prona e ventila??o mec?nica, al?m do tempo de interna??o (UTIP e no hospital). Para a compara??o entre os grupos GP e GC foram utilizados os testes de Mann-Whitney e do Qui-Quadrado. Para a an?lise longitudinal optou-se por ANOVA de medidas repetidas, utilizando o BH (ml/kg/dia), a diurese (ml/kg/h) e a quantidade de furosemida(mg/kg/dia) durante um per?odo classificado de D1 a D4 (sendo D1 o primeiro dia de ventila??o mec?nica no GC e o dia imediatamente anterior ? prona no GP). O desfecho principal foi o aumento da diurese e melhora do balan?o h?drico nos pacientes pronados. O desfecho secund?rio foi a diminui??o no tempo de ventila??o mec?nica e de interna??o em UTIP e no hospital. Resultados: foram inclu?dos 84 pacientes e, ap?s as perdas, permaneceram 77 (GP=37 e GC= 40). Em termos de idade, sexo, patologias, escores de mortalidade, ?bito, uso de drogas vasoativas e ocorr?ncia de intercorr?ncias os grupos foram semelhantes. Atrav?s de compara??o entre os grupos n?o houve melhora significativa na diurese, balan?o h?drico, tempo de ventila??o mec?nica e de interna??o em UTIP. Com rela??o ao uso de diur?ticos, houve maior uso de furosemida (P<0,001) e de espironolactona (P=0,04) no GP. Quando realizada an?lise longitudinal de medidas repetidas de D1 a D4, evidenciou-se que tanto o GP quanto o GC tiveram melhora da diurese e do balan?o h?drico, com melhora mais significativa de D1 para D2 no GP (P=0,034). No entanto, ao se verificar essa melhora, percebeu-se que ela tamb?m estava relacionada ao uso de diur?ticos. Conclus?o: Ao longo dos dias de ventila??o mec?nica estudados (D1 a D4), houve melhora tanto na diurese quanto no balan?o h?drico dos pacientes de ambos os grupos, sem evidenciar-se, no entanto, superioridade do grupo prona em rela??o ao controle.

Die Anwendung von Birkenblättern (Betulae folium) erfolgt zur Durchspülung der Harnwege. In der vorliegenden Arbeit wurde die Wirkungsweise der Birkenblätter auf verschiedenen Ebenen der Phytopharmakaforschung untersucht. Zunächst wurde in-vitro die Beeinflussung der Metallopeptidasen Neutrale Endopeptidase (NEP, EC 3.4.24.11), Angiotensin-Converting-Enzym (ACE, EC 3.4.15.1) und Leucin-Aminopeptidase (LAP, EC 3.4.11.2) durch Birkenblätterextrakte, -fraktionen und reine Naturstoffe untersucht. Die Auftrennung eines Methanol- und eines Ethylacetatextraktes führte nicht zur Gewinnung einzelner, für die Gesamtwirkungen der Extrakte verantwortlicher Fraktionen bzw. Komponenten. Die Eigenschaft der Flavonoide als wirksamkeitsmitbestimmende Inhaltsstoffe konnte jedoch bestätigt werden. Ein systematisches Screening von Flavonoiden ergab u.a., dass das Ausmaß der Enzymhemmung von der Anzahl der freien phenolischen OH-Funktionen bestimmt wurde und dass Flavonoidaglyka stärker die Enzyme hemmten, als die im Pflanzenmaterial vorliegenden Glykoside (IC50 NEP: Myricetin 42 Mikromol/L, Quercetin 192 Mikromol/L). Die in der Birkenrinde vorkommenden Triterpene Betulinsäure und Betulinol wurden als starke Inhibitoren der LAP erkannt (IC50 LAP: 7,3 +/- 1,4 bzw. 8,8 +/- 1,78 Mikromol/L). In einem nächsten Abschnitt der Arbeit wurden die Absorptionseigenschaften von Hyperosid und Rutin mit einem In-vitro-Perfusionsmodell am isolierten Rattendünndarm untersucht. Sowohl Rutin als auch Hyperosid traten unverändert als Glykoside durch den Darm in das Akzeptorkompartiment über. Auch in Form eines Birkenblätterextraktes wurde Hyperosid am Rattendünndarm absorbiert, der Extrakt veränderte jedoch nicht die Absorptionsrate. Als Mechanismus wurde der passive Transport durch die Poren der Tight junctions der Dünndarmzellen angenommen. Abschließend wurde eine Pilotstudie (n=14) durchgeführt, in der das ausgeschiedene Harnvolumen nach einmaliger Einnahme eines Birkenblättertees im Vergleich zu einer entsprechenden Menge Leitungswasser bestimmt wurde. Bei 50 % der Probanden wurde innerhalb der vierstündigen Testphase eine Zunahme der Harnproduktion beobachtet, bei den anderen 50 % stellte sich eine gegensätzliche Reaktion auf Tee und Placebo ein. Eine signifikante Erhöhung der Harnproduktion konnte somit, unter dem angegebenen Studiendesign, nicht nachgewiesen werden. / Irrigation of the urinary tract is the therapeutic indication for Birch leaf (Betulae folium). In the present thesis, effects and efficacy of Birch leaves were investigated in various fields of medicinal plant research. The effects of Birch leaf extracts, their fractions, and pure natural compounds on the metallopeptidases - Neutral Endopeptidase (NEP, EC 3.4.24.11), Angiotensin Converting Enzyme (ACE, EC 3.4.15.1), and Leucine Aminopeptidase (LAP, EC 3.4.11.2) - were investigated in vitro. Phytochemical separation of extracts obtained by methanol and ethyl acetate did not result in more active fractions compared to those of the whole extracts. The ability of flavonoids to contribute to the efficacy reached by Birch leaf extracts, could be confirmed. A systematic screening could show that the inhibitory potency of flavonoids is dependent on the number of phenolic hydroxyl functions in their chemical structure. Aglycones of flavonoids were more active than their corresponding glycosides occurring in the plant material (IC50 NEP: myricetin 42 mikromol/L, quercetin 192 mikromol/L). Betulinic acid and betulinol, triterpenes of the bark of Betula, inhibited LAP strongly by reaching an IC50 of 7,3 +/- 1,4 mikromol/L and 8,8 +/- 1,78 mikromol/L, respectively. Furthermore, this thesis showed the absorption profiles of hyperoside and rutin in an isolated small intestine model of the rat. Both glycosides were detected in the acceptor compartment without being metabolised. Administration of hyperoside by a Birch leaf extract did not influence the absorption rate. A passive transport through the pores of the tight junctions, localized between the intestinal cells, was considered to be the mechanism of absorption of the flavonol glycosides. Finally, a human pilot study (n=14) was carried out. The excreted urinary volume was determined after a single intake of a Birch leaf infusion or tap water. An increased urine output after 4 hours of the test period was found in 50% of the volunteers. In the contrary, an opposite effect was determined in 50% of the volunteers after administration of the herbal infusion and of a placebo solution. Thus, no significant increase of urine volume could be observed under these test conditions.