RESUMO OBJETIVOS: Examinamos os efeitos do tadalafil em um dos inibidores da fosfodiesterase tipo 5 (PDE5) em um modelo de rato com obstrução ureteral unilateral parcial e completa (UUO). MÉTODOS: Os ratos foram divididos em cinco grupos: sham (n = 6), obstrução ureteral unilateral parcial (PUUO, n = 6), PUUO com tadalafil (PUUO T; Cialis, 10 mg/72 h, intragástrica; Lilly, Indianapolis, Indiana, EUA), completa obstrução ureteral unilateral (CUUO, n = 6) e CUUO com tratamento com tadalafil (CUUO T). RESULTADOS: Quinze dias após a UUO, o ureter apresentou alterações nas camadas de urotélio e infiltração significativa de células inflamatórias nos grupos PUUO e CUUO. Em comparação com os grupos sham, PUUO e CUUO, houve um aumento grave da infiltração de células inflamatórias. O epitélio urotelial exibiu degeneração e perda celular devido às células epiteliais inchadas, atróficas e desnudas nos grupos PUUO e CUUO. Nos grupos PUUO T e CUUO T, o urotélio revelou menor degeneração e perda de células epiteliais. Nós mostramos que a expressão da actina do músculo liso-α (α-SMA) e do fator de crescimento transformador-β (TGF-β) foram exibidas como sub-regulação nos grupos PUUO e CUUO. A expressão do TGF-β foi diminuída positivamente correlacionada com a da α-SMA nos grupos de terapia com tadalafil, PUUO T e CUUO T. CONCLUSÃO: O tadalafil do inibidor da fosfodiesterase tipo 5 reduziu as expressões α-SMA e TGF-β nos ureteres obstruídos, medidos por exames bioquímicos. Além disso, o tadalafil diminuiu a degeneração do urotélio devido à diminuição da perda de células epiteliais e da infiltração de células inflamatórias. Nossos resultados mostram que o tadalafil previne ou retarda o início da inflamação do ureter e degeneração urotelial em ratos com UUO.

SUMMARY OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

ABSTRACT Aim: URS is a very commonly used procedure for treatment of ureter stones. Increased hydrostatic pressure in the collecting system linked to fluids used during the procedure may cause harmful effects on the kidney. The aim of this study is to determine whether the URS procedure has a negative effect on the kidney by investigating NGAL, KIM-1, FABP and Cys C levels in urine. Material and Methods: This study included 30 patients undergoing ureterorenoscopy (URS) for ureter stones. Urine samples were collected 5 times; before the URS procedure (control) and at 1, 3, 5 and 12 hours following the procedure. NGAL, KIM-1, FBAP and Cys C levels were measured in urine and compared with the control values. Results: The NGAL levels in urine before the procedure and at 1, 3, 5 and 12 hours after the procedure were 34.59±35.34; 62.72±142.32; 47.15±104.48; 45.23±163.16 and 44.99±60.79ng/mL, respectively (p=0.001). Similarly, the urinary KIM-1, FABP and Cys C levels were found to increase compared to control values; however this increase did not reach statistical significance (p >0.05). Conclusions: After the URS procedure, there were important changes in NGAL, FABP, KIM-1 and Cys C levels. These changes reached statistical significance for NGAL, but did not reach significance for the other parameters. In conclusion, the URS procedure significantly affects the kidney; however, this effect disappears over time.

RESUMO Objetivo: Este ensaio aleatório prospectivo tem por objetivo verificar se existe uma associação entre o programa de administração de nutrição enteral e os hormonios leptina e grelina, os quais funcionam no metabolismo energético. Métodos: Este estudo incluiu 38 pacientes de Unidades de Terapia Intensiva, com idades entre os 18 e os 85 anos, que receberam nutrição enteral. Os pacientes foram escolhidos aleatoriamente para receberem nutrição enteral utilizando infusão contínua (n=19) ou intermitente (n=18). Além de exames bioquímicos de rotina, foram colhidas amostras de sangue dos pacientes para análises dos níveis de leptina e grelina no 1º, 7º e 14º dias de nutrição enteral. Resultados: Não houve diferença estatística significante entre os grupos em relação a dados descritivos e variáveis categóricas tais como doenças subjacentes, complicações, utilização de esteroides e outros (p>0,05). A diminuição no número de leucócitos e nos níveis de creatinina e proteína C-reativa com o tempo foi estatisticamente significativa (p=0,010, p=0,026, p<0,001, respetivamente). Não existiu diferença com significância estatística entre os grupos em relação aos níveis de leptina e grelina (p=0,982 e p=0,054). Embora os níveis de leptina não mudaram com o tempo, os níveis de grelina de ambos os grupos foram significativamente superiores no 7° e 14° dias quando comparados aos verificados na análise do primeiro dia (p=0,003). Conclusão: Este estudo revelou que os programas de nutrição enteral contínua e intermitente foram bem tolerados com pequenas complicações apresentadas pelos pacientes em Unidades de Terapia Intensiva. O padrão de administração de nutrição enteral por si só não afetou os níveis de leptina e grelina. Estudos controlados aleatórios em coortes maiores são necessários para verificar qual programa de administração de nutrição enteral, intermitente ou a contínuo, é mais adaptável ao padrão de secreção diurno de hormônios metabólicos.

ABSTRACT Objective: The aim of this prospective randomized trial is to verify whether there is an association between the methods of administration of enteral nutrition and the leptin and ghrelin hormones, which have a major role in the regulation of energy metabolism. Methods: This study enrolled 38 enteral-fed patients aged 18 to 85 in the Intensive Care Unit. The patients were prospectively randomized to receive either continuous infusion (n=19) or intermittent feeding (n=18) of enteral nutrition. In addition to routine biochemical assays, blood samples were taken from the patients for leptin and ghrelin analyses on the 1th, 7th, and 14th days of enteral nutrition. Results: There was no statistically significant difference between the groups regarding descriptive statistics and categorical variables such as underlying diseases, complications, steroid use and others (p>0.05). The decrease in the number of white blood cells and in creatinine and C-reactive protein levels over time were statistically significant (p=0.010, p=0.026, p<0.001 respectively). There was no statistically significant difference between the groups with respect to leptin and ghrelin levels (p=0.982 and p=0.054). Leptin levels did not change over time; however, the ghrelin levels of both groups were significantly higher on the 7th and 14th days than on the first day of analysis (p=0.003). Conclusion: This study revealed that both continuous and intermittent enteral nutrition feeding regimens were well tolerated in Intensive Care Unit patients showing minor complications. The method of administration of enteral nutrition alone did not affect the leptin and ghrelin levels. Randomized controlled large cohort trials are needed to to compare intermittent and continuous enteral nutrition to determine which one is more adaptable to diurnal patterns of secretion metabolic hormones.

ABSTRACT Introduction Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). Materials and Methods Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. Results Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p<0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p<0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p<0.05). Conclusion In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.