Caracterização dos mecanismos de ação da imunoterapia intravesical com P-MAPA envolvendo as vias de sinalização dor receptores Toll-like (TLR) 2 e 4 na progressão do câncer de bexiga não-músculo invasivo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An update on metabolic assessment in patients with urinary lithiasis

The objective of this study was to evaluate the prevalence of urinary metabolic abnormalities in patients with urolithiasis and their potential risk factors.A total of 905 stone patients were evaluated in a prospective trial from February 2000 to January 2012. Inclusion criteria were as follows: history and/or imaging tests confirming at least 2 separate or concurrent stone episodes; creatinine clearance a parts per thousand yen60 mL/min; and negative proteinuria and urine culture. Metabolic study consisted of two 24-h urine collections separated by a period of 3 months for dosing Ca, P, uric acid, Na, K, Mg, oxalate, and citrate. Serum levels of Ca, P, uric acid, Na, K, Cl, Mg, creatinine, and glucose were assessed. Urinary pH and urinary acidification tests were also performed.A total of 735 patients were included, with a mean age of the 40 +/- A 1.0 year; 96.8 % of patients presented diagnosis of one or more urinary metabolic abnormalities. The most prevalent metabolic abnormalities were hypercalciuria (50.8 %), hypomagnesuria (50.1 %), hypocitraturia (35.4 %), and hyperuricosuria (30.7 %). Body weight was significantly higher in patients with hyperuricosuria (81.20 +/- A 15.67 kg vs. 70.17 +/- A 14.13 kg, respectively, p = 0.001). Urinary sodium was significantly higher in patients with hypercalciuria than without (246.97 +/- A 103.9 mEq/24 h vs. 200.31 +/- A 91.6 mEq/24 h, p = 0.001) and hyperuricosuria compared to without (283.24 +/- A 107.95 mEq/24 h vs. 198.57 +/- A 85.3 mEq/24 h, p = 0.001).Urinary metabolic disturbances were diagnosed in 96.8 % of patients in the study. These results warrant metabolic study and follow-up in patients with recurrent lithiasis in order to decrease recurrence rate through specific treatments, modification in alimentary, and behavioral habits.

Fetal kidney programming by severe food restriction: effects on structure, hormonal receptor expression and urinary sodium excretion in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterações ultrassonográficas renais e vesicais de ovinos confinados e suplementados com cloreto de amônio

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Herpes zoster-associated acute urinary retention in immunocompetent patient

Herpes zoster-associated urinary retention is an uncommon event related to virus infection of the S2-S4 dermatome. The possible major reasons are ipsilateral hemicystitis, neuritis-induced or myelitis-associated virus infection. We report a case of a 65-year-old immunocompetent female patient who presented an acute urinary retention after four days under treatment with valacyclovir for gluteal herpes zoster. The patient had to use a vesical catheter, was treated with antibiotics and corticosteroids and fully recovered after eight weeks.

Phospho-mTOR in non-tumour and tumour bladder urothelium: Pattern of expression and impact on urothelial bladder cancer patients

Urothelial bladder carcinoma (UBC) is heterogeneous in its pathology and clinical behaviour. Evaluation of prognostic and predictive biomarkers is necessary, in order to produce personalised treatment options. The present study used immunohistochemistry to evaluate UBC sections containing tumour and non-tumour areas from 76 patients, for the detection of p-mTOR, CD31 and D2-40 (blood and lymphatic vessels identification, respectively). Of the non-tumour and tumour sections, 36 and 20% were scored positive for p-mTOR expression, respectively. Immunoexpression was observed in umbrella cells from non-tumour urothelium, in all cell layers from non-muscle-invasive (NMI) tumours (including expression in superficial cells), and in spots of cells from muscle-invasive (MI) tumours. Positive expression decreased from non-tumour to tumour urothelium, and from pTl/pTis to pT3/pT4 tumours; however, the few pT3/pT4 positive cases had worse survival rates, with 5-year disease-free survival being significantly lower. Angiogenesis occurrence was impaired in pT3/pT4 tumours that did not express p-mTOR. In conclusion, p-mTOR expression in non-tumour umbrella cells is likely a reflection of their metabolic plasticity, and extension to the inner layers of the urothelium in NMI tumours is consistent with an enhanced malignant potential. The expression in cell spots in a few MI tumours and absence of expression in the remaining tumours is intriguing and requires further research. Additional studies regarding the up- and downstream effectors of the mTOR pathway should be conducted.

Role of alpha1 and alpha2-adrenoceptors of the lateral hypothalamic area on urinary excretion caused by centrally administered angiotensin II

To determine whether central α1 and α2-adrenergic mechanisms are involved in urinary sodium and potassium excretion and urine volume induced by angiotensin II (ANGII), these renal parameters were measured in volume-expanded Holtzman rats with cannulas implanted into lateral ventricle (LV) and lateral hypothalamus (LH). The injection of ANGII into LV in rats with volume expansion reduced the sodium, potassium and urine excretion in comparison to the control injections of isotonic saline, whereas prazosin (α1 antagonist) potentiated these effects. Clonidine (α2 agonist) and yohimbine (α2 antagonist) injected into LH previous to injection of ANGII into LV also abolished the inhibitory effect of ANGII. These results suggest that the discharge of central alpha-adrenergic receptors has dual inhibitory and excitatory effect on antinatriuretic, antikaliuretic and antidiuretic effect induced by central ANGII in volume-expanded rats. © 1995.

Urinary flow in children: correlation with age, body height and body surface area

Peak flow rate data (Qmax) are important for diagnosis of lower urinary tract obstruction. However, the lack of uroflowmetry studies in children, makes their interpretation difficult. With this aim, we studied 167 boys classified in four groups according to their age (G1: n = 48, 6-7 years; G2: n = 43, 8-9 years; G3: n = 37, 10-11 years; G4: n = 39, 12-14 years). We studied in all children, weight, height, body surface area, peak flow rate (Qmax) and the correspondant urinary volume (Vol). Means and standard deviations of Qmax (ml/sec) were: 15 +/- 5 (G1), 15 +/- 5 (G2), 17 +/- 5 (G3) and 22 +/- 7 (G4) respectively. Corresponding urinary volumes (Vol) (mean standard deviation-in ml) were: G1 = 123 +/- 75; G2 = 122 +/- 79; G3 = 158 +/- 96 and G4 = 162 +/- 101. We found a significant correlation (p < 0,01) between Qmax and Vol in groups G2, G3 and G4; and between Qmax and height in groups G1 and G4. The authors demonstrated a positive correlation between maximum flow and voided volume, and an increase of Qmax with age.

Bladder augmentation in rabbits with anionic collagen membrane, with or without urotelial preservation. Cistometric and hystologic evaluation

The use of bowel segments to perform bladder augmentation is associated with several metabolic and surgical complications. A great variety of synthetic materials, biodegradable or not, have been tested. Collagen-based biomaterials have shown effectiveness for the regeneration and obtainment of a functional bladder. Assess the functional and histological response of the rabbit bladder to anionic collagen membrane (ACM), either when it is anastomosed to the bladder or it is placed onto bladder after vesicomyectomy. In 15 male rabbit a partial cystectomy was performed. After 4 weeks they were divided in 3 groups. Group 1 (G1) - bladder augmentation with ACM. Group 2 (G2) ACM is placed onto bladder after vesicomyectomy. Group 3 (G3) control group. Maximal bladder capacity (MBC) and weight were assessed with 4 (M1), 8 (M2) and 12 (M3) weeks after partial cystectomy. In M3 was performed the sacrifice and extraction of the bladder and kidneys for anatomopathologic study. There were neither bladder stones, nor implant extrusion in M3. There was a significant increase in MBC in G1 and G2 (p<0.05), but no statistical differences in G3 (p=0.35). There is no significant difference comparing G1 and G2. In M3, both groups have shown a bigger MBC than G3 (p<0.05). The microscopic assessment showed an inflammatory reaction in the bladder augmented, with urothelium preserved. The ACM was effective for the increase of MBC. The bladders with preservation of the urothelium have shown an extensive inflammatory process.

Structural alterations of the bladder induced by detrusor instability. experimental study in rabbits

The aim of this study was to evaluate the histopathological and immunohistochemical alterations induced by detrusor instability in the bladder of rabbits submitted to partial bladder outlet obstruction. Thirty male Norfolk rabbits were divided into 2 groups, a clinical control and a group with detrusor instability. Urine culture, cystometric study, histopathological and immunohistochemical analysis were performed in all animals prior to surgery (M1) and 4 weeks after-surgery (M2). Partial obstruction (G2) resulted in a 2.5 fold increment (p < 0.05) in bladder weight when compared to control (G1). Four weeks after surgery, 93% of animals in G2 developed cystitis. Partial obstruction resulted in detrusor instability at M2 and bladder capacity was significantly increased (p < 0.05) from M1 to M2. The incidence of mild to moderate mucosal and adventitious fibrosis at M2 was higher in G2 (p < 0.05) when compared to G1. Inflammatory reaction at M2 was statistically higher (p < 0.05) in G2. There was no difference in muscular hypertrophy between M1 and M2 in G1. However, 67% of G2 bladders showed a moderate to intense muscular hypertrophy at M2. Hyperplasia of the epithelium was also increased in G2 when M1 and M2 were compared (p < 0.05). Detrusor instability induced by partial bladder outlet obstruction caused significant histopathological and immunohistochemical alterations in the bladder of rabbits.

Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3-adrenoceptor activation and α1-adrenoceptor blockade

Mirabegron is the first β3-adrenoceptor (AR) agonist approved for treatment of overactive bladder syndrome (OAB). This study aimed to investigate the effects of β3-adrenoceptor (AR) agonist mirabegron in mouse urethra. The possibility that mirabegron exerts α1-AR antagonism was also tested in rat smooth muscle preparations presenting α1A- (vas deferens and prostate), α1D- (aorta) and α1B-AR (spleen). Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [(3) H]Prazosin to membrane preparations of HEK 293 cells expressing each of the human α1-ARs, as well as β-AR mRNA expression and cyclic AMP measurements in mouse urethra were performed. Mirabegron produced concentration-dependent urethral relaxations that were right shifted by the selective β3-AR antagonist L 748,337, but unaffected by β1- and β2-AR antagonists (atenolol and ICI 118,551, respectively). Mirabegron-induced relaxations were enhanced by the phosphodiesterase-4 inhibitor rolipram, and this agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the α1-AR agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of α1-AR in urethra, vas deferens and prostate (α1A-AR, pA2  ≅ 5.6) and aorta (α1D-AR, pA2  ≅ 5.4), but not in spleen (α1B-AR). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant α1A- and α1D-ARs (pKi ≅ 6.0). The effects of mirabegron in urethral smooth muscle are the result of β3-AR agonism together with α1A / α1D-AR antagonism.

Sepsis and AKI in clinical emergency room patients: the role of urinary NGAL

Few studies have investigated the predictive properties of urinary (u) NGAL as an AKI marker in septic population. This study evaluated the efficacy of uNGAL as predictor of AKI and death in septic patients admitted to the clinical emergency room (ER). We prospectively studied patients with sepsis admitted to the ER. Urine was analyzed for NGAL within the first 24 hours after admission (classified as NGAL1), between 24 and 48 h (NGAL2), and at moment of AKI diagnosis (NGAL3). Among 168 septic patients admitted to ER, 72% developed AKI. The uNGAL and its relationship with creatinine (Cr) were high in septic patients but statistically higher in those with sepsis and AKI. The uNGAL1 and uNGAL2, as well as uNGAL1/uCr1 and uNGAL2/uCr2, were good predictors for AKI (AUC-ROC 0.73, 0.70, 0.77, and 0.84, resp.). The uNGAL1 and uNGAL1/uCr1 were poor predictors for death (AUC-ROC 0.66 and 0.68, resp.), whereas uNGAL2 and uNGAL2/uCr2 were better predictors (AUC-ROC 0.70 and 0.81, resp.). The uNGAL is highly sensitive but nonspecific predictor of AKI and death in septic patients admitted into ER.

Efeitos das formulações nanoestruturadas de doxorrubicina e cisplatina em dispersão de óxido de grafeno reduzido no tratamento da progressão do câncer de bexiga Não-músculo invasivo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)