Publications by authors named "Silvio Tucci"

44 Publications

Expression of MicroRNAs (miR-15b, miR-16, miR-138, miR-221, and miR-222) as Biomarkers of Endothelial Corpus Cavernosum Dysfunction in a Diabetic Alcoholic Murine Model.

Sex Med 2021 Apr 3;9(2):100326. Epub 2021 Mar 3.

Division of Urology, University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil.

Introduction: MicroRNAs (miRNAs) are short noncoding RNA molecules that regulate gene expression and are related to endothelial dysfunction (EnD). Recently, miRNAs have also been explored as potential biomarkers and target molecular therapy of erectile dysfunction (ED). Could the miRNAs be the tip of the iceberg of chronic arterial disease foreshadowed by the ED?

Aim: To investigate the expression of miR-15b, miR-16, miR-138, miR-221, and miR-222 in corpus cavernosum (CC) and peripheral blood in a rat model of endothelium dysfunction secondary to diabetes (DM) and alcohol consumption to assess potential endothelial lesion biomarkers.

Methods: Twenty males Wistar rats were divided into 4 groups: control group (C), alcohol consumption group (A), diabetic group (D), diabetic-alcohol consumption group (D + A). DM was alloxan-induced and alcohol consumption was through progressive increase of ethanol concentration in drinkable water. After 7 weeks, miRNAs expressions from CC and blood sample were evaluated by real-time PCR. Functional assessment of CC was performed in an acetylcholine endothelium-dependent relaxation pharmacological study.

Main Outcome Measure: miRNA expression in CC and blood were evaluated; pharmacological study in CC strips was conducted to validate EnD.

Results: We found that 3 miRNAs (miR-16, miR-221, and miR-222) were downregulated in the CC in the D+A group, while all 5 miRNAs were downregulated in the blood of D and D + A groups. The endothelium-dependent relaxation induced by acetylcholine was significantly decreased in groups A, D, and D + A. Diagnostic accuracy estimated by AUC, to discriminating groups A, D, and D + A from controls, was superior to >0.9 in all plasmatic miRNAs.

Conclusion: miRNAs downregulation was identified in both CC and blood notably in DM associated with alcohol consumption animals (D + A), the greatest endothelial injury potential group. Serum miRNAs have also demonstrated high diagnostic accuracy properties in predicting CC relaxation dysfunction labeling EnD. RB Tiraboschi, FSL Neto, DP da Cunha Tirapelli, et al. Expression of MicroRNAs (miR-15b, miR-16, miR-138, miR-221, and miR-222) as Biomarkers of Endothelial Corpus Cavernosum Dysfunction in a Diabetic Alcoholic Murine Model. Sex Med 2021;9:100326.
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http://dx.doi.org/10.1016/j.esxm.2021.100326DOI Listing
April 2021

Right Atrium Tumor Extension Through the Inferior Vena Cava. Considerations About Nine Cases Operated Under Cardiopulmonary Bypass.

Braz J Cardiovasc Surg 2019 12 1;34(6):723-728. Epub 2019 Dec 1.

Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Department of Surgery and Anatomy Ribeirão Preto SP Brazil Department of Surgery and Anatomy, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Introduction: Adrenocortical and renal cell carcinomas rarely invade the right atrium (RA). These neoplasms need surgical treatment, are very aggressive and have poor prognostic and surgical outcomes.

Case Series: We present a retrospective cohort of nine cases of RA invasion through the inferior vena cava (four adrenocortical carcinomas and five renal cell carcinomas). Over 13 years (2002-2014), nine patients were operated in collaboration with the team of urologists. Surgery was possible in all patients with different degrees of technical difficulty. All patients were operated considering the imaging examinations with the aid of CPB. In all reported cases (renal or suprarenal), the decision to use CPB with deep hypothermic circulatory arrest (DHCA) on surgical strategy was decided by the team of urological and cardiac surgeons.

Conclusion: Data retrospectively collected from patients of public hospitals reaffirm: 1) Low incidence with small published series; 2) The selected cases did not represent the whole historical casuistry of the hospital, since they were selected after the adoption of electronic documentation; 3) Demographic data and references reported in the literature were presented as tables to avoid wordiness; 4) The series highlights the propensity to invade the venous system; 5) Possible surgical treatment with the aid of CPB in collaboration with the urology team; 6) CPB with DHCA is a safe and reliable option; 7) Poor prognosis with disappointing late results, even considering the adverse effects of CPB on cancer prognosis are expected but not confirmed.
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http://dx.doi.org/10.21470/1678-9741-2019-0053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894024PMC
December 2019

DDAH1 and DDAH2 polymorphisms associate with asymmetrical dimethylarginine plasma levels in erectile dysfunction patients but not in healthy controls.

Nitric Oxide 2019 11 5;92:11-17. Epub 2019 Aug 5.

Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Brazil. Electronic address:

Erectile Dysfunction (ED) is one of the main complaints of aging male. A reduced production of Nitric Oxide (NO) may be involved in ED pathogenesis. NO is synthesized from l-Arginine, and asymmetrical dimethylarginine inhibits all NO synthases. DDAH1 and DDAH2 are genes that encode enzymes responsible for metabolizing ADMA. We aimed to assess whether: 1) ADMA and nitrite levels associated with ED risk and with symptoms intensity; and whether 2) DDAH1 and DDAH2 gene polymorphisms associate with changes in biochemical data, and with ED risk and symptoms intensity. In this study were included 98 healthy controls and 130 ED patients. ADMA levels were measured by ELISA and nitrite levels by Chemiluminescence. DDAH1 and DDAH2 polymorphisms were assessed by Taqman assays. We found that ED had increased nitrite levels and lower ADMA levels than Control group (P < 0.05). We found a significant correlation of ADMA with Nitrite levels only in ED (B = -0.57, P < 0.001). Genotypes and haplotypes of DDAH1 were associated with ADMA levels in ED (P < 0.05), while haplotypes of DDAH2 were associated with levels of nitrite in ED (P < 0.05). Erectile dysfunction patients show an association between DDAH1 and DDAH2 polymorphisms with ADMA levels, which in turn are negatively correlated with nitrite levels. This is not evident on healthy controls.
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http://dx.doi.org/10.1016/j.niox.2019.08.001DOI Listing
November 2019

Histogram Analysis of Adrenal Lesions With a Single Measurement for 10th Percentile: Feasibility and Incremental Value for Diagnosing Adenomas.

AJR Am J Roentgenol 2018 12 9;211(6):1227-1233. Epub 2018 Oct 9.

1 Department of Internal Medicine, Radiology Division, Ribeirao Preto School of Medicine, University of Sao Paulo, Hospital Clinicas, Avenue Bandeirantes 3900, Campus Monte Alegre, Ribeirao Preto 14049-900, Sao Paulo, Brazil.

Objective: Our purpose was to assess whether histogram analysis of adrenal lesions from a single measurement of mean attenuation and SD, using a threshold of 10% of negative voxels, can replace voxel counting while maintaining diagnostic accuracy.

Materials And Methods: In a 4-year period, 325 adrenal lesions were detected on CT examinations of 308 consecutive patients. After exclusions, 91 patients with 108 lesions, including 20 malignant lesions and 88 adenomas (defined by histologic results or follow-up), were enrolled. Two observers retrospectively measured lesion size, mean attenuation value, and SD attenuation value and generated a pixel histogram. The 10th percentile (P10) was obtained from the conventional histogram analysis and was also calculated from the following formula: P10 = mean attenuation - (1.282 × SD). Diagnostic accuracies of the mean attenuation criterion, histogram analysis, and calculated 10th percentile were compared.

Results: The study group was composed of 74 patients with 88 adenomas and 17 patients with 20 malignant lesions, including seven adrenocortical carcinomas and 13 metastases; 93.1% of histograms showed normal distribution. The correlation between histogram analysis and calculated 10th percentile was 0.9827 and 0.9843 for reader 1 and 2 (p < 0.00001 for both). For both readers, sensitivity and specificity of the mean attenuation analysis were 65.9% (95% CI, 55.0-75.7%) and 100.0% (95% CI, 83.2-100%). The sensitivity and specificity of histogram analysis and calculated 10th percentile were the same, 87.5% (95% CI, 78.7-93.6%) and 95.0% (95% CI, 75.1-99.8%), for both readers. The increment increase in sensitivity was significant (p < 0.001), whereas the decrease in specificity was not (p = 0.15).

Conclusion: For most adrenal lesions, the pixel attenuation has a gaussian distribution, allowing estimation of 10th percentile with a single measurement. The accuracy of histogram analysis and calculated 10th percentile outperformed the mean attenuation as a diagnostic criterion for nonfunctioning adenomas.
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http://dx.doi.org/10.2214/AJR.17.19159DOI Listing
December 2018

Relationship between asymmetric dimethylarginine, nitrite and genetic polymorphisms: Impact on erectile dysfunction therapy.

Nitric Oxide 2017 Dec 23;71:44-51. Epub 2017 Oct 23.

Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Brazil. Electronic address:

Sildenafil is the most used treatment of erectile dysfunction, however a large part of patients do not respond to therapy. This drug enhances nitric oxide (NO) signaling, and therefore factors that alter NO production may impact this drug responsiveness. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all NO synthases, and is metabolized by Dimethylarginine Dimethilaminohydrolase (DDAH) 1 and 2. Here we aimed to assess the relationship between plasma levels of ADMA and nitrite (marker of nitric oxide production) with Sildenafil responsiveness. We also studied genetic polymorphisms in DDAH1 and DDAH2 genes and their relation with biochemical and clinical data. Were included here 140 patients, divided in Clinical Erectile Dysfunction (CED) or Post-Prostatectomy Erectile Dysfunction (PPED) groups. Erectile function was evaluated before and after Sildenafil on-demand treatment using the International Index for Erectile Function Questionnaire. We have found that nitrite was associated with worse response to Sildenafil (r = - 0.25, P = 0.040). rs1554597 and rs18582 DDAH1 polymorphisms were associated with changes in ADMA levels in CED (B = - 0.23, P = 0.002; B = - 0.15, P = 0.017 for both variant genotypes, respectively). Finally, DDAH2 polymorphisms were associated with altered responsiveness to Sildenafil in PPED (B = +0.19, P = 0.027).
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http://dx.doi.org/10.1016/j.niox.2017.10.006DOI Listing
December 2017

Validation of self - confidence scale for clean urinary intermittent self - catheterization for patients and health - caregivers.

Int Braz J Urol 2017 May-Jun;43(3):505-511

Divisão de Urologia, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo- USP - Ribeirão Preto,SP, Brasil.

Objective: To validate a measurement instrument for clean intermittent self-catheterization for patients and health-caregivers.

Material And Methods: Methodological study of instrument validation performed at a Rehabilitation Center in a University hospital for patients submitted to clean intermittent self-catheterization and their health-caregivers. Following ethical criteria, data were collected during interview with nurse staff using a Likert question form containing 16 items with 5 points each: "no confidence"=1, "little confidence"=2, "confident"=3, "very confident"=4 and "completely confident"=5. Questionnaire called "Self- Confident Scale for Clean Intermittent Self-catheterization" (SCSCISC) was constructed based on literature and previously validated (appearance and content).

Results: The instrument was validated by 122 patients and 119 health-caregivers, in a proportion of 15:1. It was observed a good linear association and sample adequacy KMO 0.931 and X2=2881.63, p<0.001. Anti-image matrix showed high values at diagonal suggesting inclusion of all factors. Screen plot analysis showed a suggestion of items maintenance in a single set. It was observed high correlation of all items with the total, alpha-Cronbach 0.944. The same results were obtained in subsamples of patients and health-caregivers.

Conclusion: The instrument showed good psychometric adequacy corroborating its use for evaluation of self-confidence during clean intermittent self-catheterization.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2015.0468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462142PMC
October 2017

Expression profiles of eNOS, iNOS and microRNA-27b in the corpus cavernosum of rats submitted to chronic alcoholism and Diabetes mellitus.

Acta Cir Bras 2017 Jan;32(1):38-45

Associate Professor, Division of Urology, Department of Surgery and Anatomy, School of Medicine of Ribeirao Preto, USP, Ribeirao Preto-SP, Brazil. Concept, design, intellectual and scientific content of the study; critical revision; supervised all phases of the study.

Purpose: : To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies.

Methods: : Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood.

Results: : Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups.

Conclusion: : The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.
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http://dx.doi.org/10.1590/s0102-865020170105DOI Listing
January 2017

Adrenocortical neoplasms in adulthood and childhood: distinct presentation. Review of the clinical, pathological and imaging characteristics.

J Pediatr Endocrinol Metab 2017 Mar;30(3):253-276

Adrenocortical tumors (ACT) in adulthood and childhood vary in clinical, histopathological, molecular, prognostic, and imaging aspects. ACT are relatively common in adults, as adenomas are often found incidentally on imaging. ACT are rare in children, though they have a significantly higher prevalence in the south and southeast regions of Brazil. In clinical manifestation, adults with ACT present more frequently with glucocorticoid overproduction (Cushing syndrome), mineralocorticoid syndromes (Conn syndrome), or the excess of androgens in women. Subclinical tumors are frequently diagnosed late, associated with compression symptoms of abdominal mass. In children, the usual presentation is the virilizing syndrome or virilizing association and hypercortisolism. Histopathological grading and ACT classification in malignant and benign lesions are different for adults and children. In adults, the described criteria are the Hough, Weiss, modified Weiss, and Van Slooten. These scores are not valid for children; there are other criteria, such as proposed by Wieneke and colleagues. In molecular terms, there is also a difference related to genetic alterations found in these two populations. This review discusses the imaging findings of ACT, aiming to characterize the present differences between ACT found in adults and children. We listed several differences between magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography-computed (PET-CT) and also performed a literature review, which focuses on studied age groups of published articles in the last 10 years regarding cortical neoplasm and imaging techniques. Published studies on ACT imaging in children are rare. It is important to stress that the majority of publications related to the differentiation of malignant and benign tumors are based almost exclusively on studies in adults. A minority of articles, however, studied adults and children together, which may not be appropriate.
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http://dx.doi.org/10.1515/jpem-2016-0080DOI Listing
March 2017

Unraveling the expression of the oncogene YAP1, a Wnt/beta-catenin target, in adrenocortical tumors and its association with poor outcome in pediatric patients.

Oncotarget 2016 Dec;7(51):84634-84644

Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.

Background: Overexpression of the oncogene yes-associated-protein-1 (YAP1) is associated with increased cell proliferation in human cancers. YAP1 is a potential target of the Wnt/beta-catenin pathway, which plays an important role in adrenocortical tumors (ACT). The role of YAP1 in adrenocortical tumorigenesis has not been assessed.

Aims: To evaluate YAP1 expression in normal adrenals and pediatric ACT and its association with disease outcome. To investigate the interaction between YAP1 and the Wnt/beta-catenin pathway in adrenocortical cells.

Results: Strong YAP1 staining was present in fetal adrenals and pediatric ACT but weak in postnatal adrenals. In pediatric ACT, YAP1 mRNA overexpression was associated with death, recurrent/metastatic disease and lower overall survival. The inhibition of the Wnt/beta-catenin pathway increased YAP1 mRNA expression. siYAP1 increased CTNNB1/beta-catenin expression and nuclear staining regardless of DLV2, moreover, it decreased cell growth and impaired cell migration.

Materials And Methods: We assessed in 42 pediatric ACT samples the YAP1 protein expression by immunohistochemistry and mRNA expression by RT-qPCR and analyzed their association with outcome. As controls, we resort 32 fetal and postnatal normal adrenals for IHC and 10 normal adrenal cortices for RT-qPCR. The interaction between YAP1 and the Wnt/beta-catenin pathway was assessed in NCI-H295 adrenocortical cells by inhibiting the TCF/beta-catenin complex and by knocking down YAP1.

Conclusion: YAP1 overexpression is a marker of poor prognosis for pediatric patients with ACT. In adrenocortical cells, there is a close crosstalk between YAP1 and Wnt/beta-catenin. These data open the possibility of future molecular therapies targeting Hippo/YAP1 signaling to treat advanced ACT.
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http://dx.doi.org/10.18632/oncotarget.12382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356687PMC
December 2016

Intermittent urethral catheterisation: the reality of the lubricants and catheters in the clinical practice of a Brazilian service.

J Clin Nurs 2016 Nov 24;25(21-22):3382-3390. Epub 2016 Aug 24.

Department of Surgery and Anatomy, FMRP-USP, Ribeirão Preto, Brazil.

Aims And Objectives: To identify how catheters and lubricants have been used among patients using intermittent urinary catheterisation in rehabilitation.

Background: The clean intermittent urinary catheterisation technique is an invasive procedure can cause discomfort, pain and urethral traumas. The use of lubricants and lubricated urinary catheters reduces the friction between the catheter and the urethral mucosa, minimising the risks.

Design: A descriptive exploratory design was used.

Methods: Quantitative and descriptive study developed at a rehabilitation centre of a University Hospital in the interior of the state of São Paulo, Brazil, at the Intermittent Urinary Catheterisation Outpatient Clinic, between June 2012-December 2014. After ethical approval, the data were collected through an interview with the support of a semistructured questionnaire, held during the nursing consultation. Among the users, patients using intermittent urinary catheterisation were interviewed, over 18 years of age and minors younger than eight years accompanied. Descriptive statistical analysis was applied.

Results: Most of 214 (100·0%) patients were interviewed were male, single, young adults and with a primary medical diagnosis of bone marrow injury and myelomeningocele. Most patients perform the urinary catheterisation between four and six times per day. For the procedure, the majority uses polyethylene (polyvinyl chloride) catheter and, as a lubricant, 2·0% lidocaine hydrochloride on the catheter itself. Many mention lack of sensitivity when passing the catheter.

Conclusion: In the study sample, a risk of urethral traumas was evidenced, related to the inappropriate use of catheters and lubricants. For the patients' safety, the professionals need to acknowledge the importance of the appropriate use of lubricants and lubricated catheters to implement evidence-based practices that mobilise public policies.

Relevance To Clinical Practice: The use of evidences demonstrates that the appropriate use of lubricants for intermittent urinary catheterisation is fundamental for patient safety and the performance of the best practices.
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http://dx.doi.org/10.1111/jocn.13466DOI Listing
November 2016

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis.

Endocr Relat Cancer 2016 06 16;23(6):481-93. Epub 2016 May 16.

Department of PediatricsRibeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil

Deregulation of the IGF system observed in human tumors indicates a role in malignant cell transformation and in tumor cell proliferation. Although overexpression of the IGF2 and IGF1R genes was described in adrenocortical tumors (ACTs), few studies reported their profiles in pediatric ACTs. In this study, the IGF2 and IGF1R expression was evaluated by RT-qPCR according to the patient's clinical/pathological features in 60 pediatric ACT samples, and IGF1R protein was investigated in 45 samples by immunohistochemistry (IHC). Whole transcriptome and functional assays were conducted after IGF1R inhibition with OSI-906 in NCI-H295A cell line. Significant IGF2 overexpression was found in tumor samples when compared with non-neoplastic samples (P<0.001), significantly higher levels of IGF1R in patients with relapse/metastasis (P=0.031) and moderate/strong IGF1R immunostaining in 62.2% of ACTs, but no other relationship with patient survival and clinical/pathological features was observed. OSI-906 treatment downregulated genes associated with MAPK activity, induced limited reduction of cell viability and increased the apoptosis rate. After 24h, the treatment also decreased the expression of genes related to the steroid biosynthetic process, the protein levels of the steroidogenic acute regulatory protein (STAR), and androgen secretion in cell medium, supporting the role of IGF1R in steroidogenesis of adrenocortical carcinoma cells. Our data showed that the IGF1R overexpression could be indicative of aggressive ACTs in children. However, in vitro treatments with high concentrations of OSI-906 (>1μM) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth.
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http://dx.doi.org/10.1530/ERC-15-0426DOI Listing
June 2016

Low expression of HLA-DRA, HLA-DPA1, and HLA-DPB1 is associated with poor prognosis in pediatric adrenocortical tumors (ACT).

Pediatr Blood Cancer 2014 Nov 23;61(11):1940-8. Epub 2014 Aug 23.

Department of Pediatrics, Ribeirão Preto Medicine School, University of São Paulo, Ribeirão Preto, Brazil.

Background: Low expression of HLA class II antigens has been associated with more aggressive disease in several human malignancies including adult adrenocortical tumors (ACT), but their clinical relevance in pediatric ACT needs to be investigated.

Procedure: This study analyzed the expression profile of three class II histocompatibility genes (HLA-DRA, HLA-DPA1, and HLA-DPB1) in 58 consecutive pediatric ACT (13 adenomas and 45 carcinomas) by quantitative real time PCR and their association with clinical and biological features. HLA-DPA1 protein level was determined by immunohistochemistry.

Results: A significant association (P < 0.01) was observed between lower expression levels of the three genes analyzed and poor prognostic factors such as age ≥ 4 years, tumor size ≥ 200 cm(3), tumor weight ≥ 100 g, and metastatic disease; the presence of an unfavorable event and death. Underexpression of the HLA-DRA, HLA-DPA1, and HLA-DPB1 genes were associated with lower 5-year event-free survival (EFS) (P = 0.017, P < 0.001, and P = 0.017, respectively). Cox multivariate analysis showed that HLA-DPA1 was an independent prognostic factor (P = 0.029) when analyzed in association with stage IV, age and tumor size. Significantly lower EFS was also observed in patients with negative/weak immunostaining for HLA-DPA1 (P = 0.002). Similar results were observed when only patients classified as having carcinomas were analyzed.

Conclusion: Our results suggest that lower expression of HLA-DRA, HLA-DPA1, and HLA-DPB1 genes may contribute to more aggressive disease in pediatric ACT. HLA-DPA1 immunostaining may represent potential aggressiveness marker in this tumor.
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http://dx.doi.org/10.1002/pbc.25118DOI Listing
November 2014

Urethral dysfunction due to alloxan-induced diabetes. Urodynamic and morphological evaluation.

Acta Cir Bras 2014 Jul;29(7):457-64

Department of Surgery and Anatomy, FMRP, USP, Ribeirao Preto, SP, Brazil.

Purpose: To evaluate the effect of short and long term alloxan-induced diabetes on bladder and urethral function of female rats, and also describing its correlated morphological alterations.

Methods: Thirty five female rats were divided into three groups: G1 (n=9), control group; G2 (n=17), six weeks alloxan-induced diabetic rats; G3 (n=9), 20 weeks alloxan-induced diabetic rats. Functional evaluation was performed by cystometry and simultaneous measurements of the urethral pressure during bladder filling and voiding. Morphological evaluation was also performed with measurement of bladder and urethral fibrosis and collagen content and thickness of lamina propria and smooth muscle layers.

Results: The peak bladder pressures and contraction amplitudes were decreased in 100% and 47% of the G3 and G2 groups respectively, when compared to control. Bladder overactivity was observed in 53% of the G2 group.

Conclusion: Alloxan-induced diabetes urethropathty in female rat was associated to bladder morphological alterations as higher thicknesses of it lamina propria, detrusor and adventicea.
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http://dx.doi.org/10.1590/s0102-86502014000700008DOI Listing
July 2014

Urethral dysfunction due to alloxan-induced diabetes. Urodynamic evaluation and action of sildenafil citrate.

Acta Cir Bras 2014 Apr;29(4):274-9

Department of Surgery and Anatomy, FMRP, USP, Ribeirao Preto, SP, Brazil.

Purpose: To evaluate the effect of diabetes mellitus and of sildenafil citrate on female urethral function.

Methods: Twenty nine female rats were divided into four groups: G1 - (n=9), normal rats; G2 - (n=6), normal rats treated with sildenafil citrate; G3 - (n=9) rats with alloxan-induced diabetes; G4 - (n=5) rats with alloxan-induced diabetes treated with sildenafil citrate. Under anesthesia, urodynamic evaluation was performed by cystometry and urethral pressure simultaneously.

Results: A significant increase in urethral pressure was observed during micturition.

Conclusion: Sildenafil citrate can partially reduced urethral pressure in diabetic female rats.
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http://dx.doi.org/10.1590/s0102-86502014000400009DOI Listing
April 2014

Altered expression of noncanonical Wnt pathway genes in paediatric and adult adrenocortical tumours.

Clin Endocrinol (Oxf) 2014 Oct 19;81(4):503-10. Epub 2014 May 19.

Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.

Context: The role of planar cell polarity (Wnt/PCP) and calcium-dependent (Wnt/Ca) noncanonical Wnt pathways in adrenocortical tumours (ACTs) is unknown.

Objectives: To investigate the gene expression of Wnt/PCP and Wnt/Ca pathways and its association with TP53 p.R337H and CTNNB1 mutations in paediatric and adult ACTs and to correlate these findings with clinical outcome.

Patients: Expression of noncanonical Wnt-related genes was evaluated in 91 ACTs (66 children and 25 adults) by qPCR and the expression of beta-catenin, P53 and protein effectors of Wnt/Ca (NFAT) and Wnt/PCP (JNK) by immunohistochemistry. TP53 and CTNNB1 genes were sequenced.

Results: TP53 p.R337H mutation frequency was higher in children (86% vs 28%), while CTNNB1 mutation was higher in adults (32% vs 6%). Mortality was higher in adults harbouring TP53 p.R337H and in children with CTNNB1 mutations. Overexpression of WNT5A, Wnt/Ca ligand, was observed in children and adults. Overexpression of MAPK8 and underexpression of PRICKLE, Wnt/PCP mediators, were observed in paediatric but not in adult cases. Cytoplasmic/nuclear beta-catenin and P53 accumulation was observed in the majority of paediatric and adult ACTs as well as NFAT and JNK. Overexpression of MAPK8 and underexpression of PRICKLE were associated with mortality in children, while overexpression of WNT5A and underexpression of PRICKLE were associated with mortality in adults.

Conclusions: In our study, TP53 p.R337H and CTNNB1 mutations correlated with poor prognosis in adults and children, respectively. We demonstrate, for the first time, the activation of Wnt/PCP and Wnt/Ca noncanonical pathway genes, and their association with poor outcome in children and adults, suggesting their putative involvement in ACTs aggressiveness.
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http://dx.doi.org/10.1111/cen.12462DOI Listing
October 2014

Sonic hedgehog signaling is active in human adrenal cortex development and deregulated in adrenocortical tumors.

J Clin Endocrinol Metab 2014 Jul 8;99(7):E1209-16. Epub 2014 Apr 8.

School of Medicine (D.C.G., L.F.L., L.M.M., C.A.S., C.E.M., L.G.T., S.T., F.R., A.C.M., L.N.R., M.C., S.R.R.A.), Ribeirao Preto Medical School-University of Sao Paulo, 14090-900 Ribeirao Preto, Brazil; School of Medicine (M.C.B.V.F., A.C.L.), University of Sao Paulo, 01246-903 Sao Paulo, Brazil; and Boldrini Children's Center (J.A.Y., S.R.B., I.A.C., M.J.M.), 13083-210 Campinas, Brazil.

Background: The sonic hedgehog (SHH) pathway plays a key role in rodent adrenal cortex development and is involved in tumorigenesis in several human tissues, but data in human adrenal glands are limited.

Objectives: The objectives of the study were to analyze the involvement of the SHH pathway in human adrenal development and tumorigenesis and the effects of SHH inhibition on an adrenocortical tumor (ACT) cell line.

Patients And Methods: Expression of SHH pathway components was evaluated by immunohistochemistry in 51 normal adrenals (33 fetal) and 34 ACTs (23 pediatric) and by quantitative PCR in 81 ACTs (61 pediatric) and 19 controls (10 pediatric). The effects of SHH pathway inhibition on gene expression and cell viability in the NCI-H295A adrenocortical tumor cell line after cyclopamine treatment were analyzed.

Results: SHH pathway proteins were present in fetal and postnatal normal adrenals and showed distinct patterns of spatiotemporal expression throughout development. Adult adrenocortical carcinomas presented with higher expression of PTCH1, SMO, GLI3, and SUFU compared with normal adult adrenal cortices. Conversely, pediatric ACTs showed lower mRNA expression of SHH, PTCH1, SMO, GLI1, and GLI3 compared with normal pediatric adrenal cortices. In vitro treatment with cyclopamine resulted in decreased GLI3, SFRP1, and CTNNB1 mRNA expression and β-catenin staining as well as decreased cell viability.

Conclusions: The SHH pathway is active in human fetal and postnatal adrenals, up-regulated in adult adrenocortical carcinomas, and down-regulated in pediatric ACTs. SHH pathway antagonism impaired cell viability. The SHH pathway is deregulated in ACTs and might provide a new target therapy to be explored.
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http://dx.doi.org/10.1210/jc.2013-4098DOI Listing
July 2014

Spindle assembly checkpoint gene expression in childhood adrenocortical tumors (ACT): Overexpression of Aurora kinases A and B is associated with a poor prognosis.

Pediatr Blood Cancer 2013 Nov 20;60(11):1809-16. Epub 2013 Jun 20.

Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Background: Pediatric adrenocortical tumors (ACT) are rare malignancies and treatment has a small impact on survival in advanced disease and the discovery of potential target genes could be important in new therapeutic approaches.

Methods: The mRNA expression levels of spindle checkpoint genes AURKA, AURKB, BUB, and BUBR1 were analyzed in 60 children with ACT by quantitative real time PCR. The anticancer effect of ZM447439, an experimental AURK inhibitor, was analyzed in a primary childhood ACT culture carrying the TP53 p.R337H mutation.

Results: A significant association was observed between malignancy as defined by Weiss score ≥3 and higher AURKA (2.0-fold, P = 0.01), AURKB (7.0-fold, P = 0.007), and BUBR1 (5.8-fold, P = 0.007) gene expression, and between unfavorable event (death or relapse) and higher expression of AURKA (6.0-fold, P = 0.034) and AURKB (17-fold, P = 0.013). Overexpression of AURKA and AURKB was associated with lower event-free survival in uni- (P < 0.001 and P = 0.006, respectively) and multivariate (P = 0.002 and P = 0.03, respectively) analysis. Significant lower Event free survival (EFS) was also observed in patients with moderate/strong immunostaining to AURKA (P = 0.012) and AURKB (P = 0.045). ZM447439 was able to induce inhibition of proliferation and colony formation in a primary childhood ACT culture carrying the TP53 p.R337H mutation.

Conclusion: Our results suggest that AURKA and AURKB overexpression in pediatric ACT may be related to more aggressive disease and the inhibition of these proteins could be an interesting approach for the treatment of these tumors.
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http://dx.doi.org/10.1002/pbc.24653DOI Listing
November 2013

Low nitric oxide bioavailability is associated with better responses to sildenafil in patients with erectile dysfunction.

Naunyn Schmiedebergs Arch Pharmacol 2013 Sep 19;386(9):805-11. Epub 2013 May 19.

Department of Pharmacology, State University of Campinas, Campinas, Sao Paulo, Brazil.

Erectile dysfunction (ED) is a multifactorial disease associated with vascular dysfunction, low nitric oxide (NO) bioavailability, and oxidative stress. However, it is not known whether low NO bioavailability and oxidative stress affect the responsiveness of ED patients to sildenafil. We tested this hypothesis by studying 28 healthy subjects (control group), 26 patients with ED without comorbidities (ED group), and 18 patients with ED and diabetes mellitus (ED/DM group). The International Index for Erectile Function (IIEF) questionnaire was used to assess the erectile function of all participants, and their responsiveness to sildenafil was assessed as the percentage of change in the five-item version of IIEF score before and after sildenafil treatment. Levels of whole blood nitrite, antioxidants markers (ferric reducing ability of plasma (FRAP) and reduced glutathione), and oxidative stress markers (thiobarbituric acid reactive substance and protein carbonyl) were determined. We found a negative correlation between whole blood nitrite levels and the responses to sildenafil in both ED groups (P<0.05). FRAP correlated negatively with the responses to sildenafil in the ED/DM group (P<0.05). No other significant associations were found. Our findings show evidence that low NO bioavailability is associated with better responses to sildenafil in patients with ED (with or without DM).
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http://dx.doi.org/10.1007/s00210-013-0882-zDOI Listing
September 2013

Hormone therapy in hypospadias surgery: a systematic review.

J Pediatr Urol 2013 Dec 19;9(6 Pt B):971-9. Epub 2013 Apr 19.

Federal University of Juiz de Fora - UFJF, Av. Rio Branco, 2985/sl. 605, Juiz de Fora, MG 36010012, Brazil. Electronic address:

Surgical correction of hypospadias is proposed to improve the aesthetic and functional quality of the penis. Hormone therapy preceding surgical correction is indicated to obtain better surgical conditions. However, there is divergence in the literature regarding the hormone therapy of choice, time of its use before surgery, appropriate dose, and route of application. To try to elucidate this matter, an electronic survey of the databases PubMed and Cochrane Central Library was conducted, limited to articles in English published since 1980. Search strategy identified 14 clinical trials that matched the inclusion criteria. Analysis was made in terms of study design, classification of hypospadias, association with chordee and cryptorchidism, type of hormone, route of application, dose and duration of treatment, penile length before and after hormone therapy, glans circumference before and after hormone therapy, adverse effects, and surgical complications. From the trials evaluated it was not possible to determine the ideal neoadjuvant treatment. A preference for use of testosterone was observed. Intramuscular administration seems to have fewer adverse effects than topical treatment. Side effects were seldom described, and treated patients were not followed on a long-term basis. The scarcity of randomized and controlled clinical trials regarding the topic impairs the establishment of a protocol. In conclusion, although preoperative hormone therapy is currently used before hypospadias surgery, its real benefit in terms of improvement of the penis and surgical results has not been defined.
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http://dx.doi.org/10.1016/j.jpurol.2013.03.009DOI Listing
December 2013

Postnatal evaluation of intrauterine hydronephrosis due to ureteropelvic junction obstruction.

Acta Cir Bras 2013 ;28 Suppl 1:33-6

Division of Urology, Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.

Purpose: Fetal hydronephrosis is a frequent finding due to advances in prenatal ultrasonography. The definition of fetal and neonatal urinary tract obstruction is a very difficult task requiring confirmation of reduced renal function and hydronephrosis. In this study we followed a series of consecutive patients with intrauterine hydronephrosis that persisted during post-natal life.

Methods: 116 newborns with antenatal hydronephrosis diagnosed by ultrasound and submitted to a specific post-natal evaluative protocol with a follow-up period of 6 years.

Results: In 45 (38.8%) of 116 patients, ureteropelvic junction (UPJ) obstruction was confirmed and surgical correction of the UPJ obstruction was done in 19 patients. From 26 children who were initially submitted to non-surgical treatment, only 6 (23%) needed a surgical approach during follow up. Overall analysis showed that surgery was performed in 25 patients with UPJ obstruction, and the others 20 patients were kept under clinical observation, since normal renal function was confirmed by scintigraphy scans.

Conclusion: Fetal hydronephrosis due to UPJ obstruction deserves careful postnatal evaluation. UPJ obstruction is the most frequent anomaly and its surgical treatment has very precise indications. The evaluative protocol was useful in identify patients that could be followed-up with a non-surgical approach.
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http://dx.doi.org/10.1590/s0102-86502013001300007DOI Listing
January 2014

Renal abscess in hyper-IgE syndrome.

Urology 2013 Feb;81(2):414-6

Division of Pediatric Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of São Paulo Faculty of Medicine of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.

Kidney disease due to Aspergillus fumigatus is a rare finding in hyper-IgE syndrome. We report a patient with autosomal dominant hyper-IgE syndrome, recurrent pneumonia, and acute necrosuppurative pyelonephritis caused by Aspergillus fumigatus with a fatal outcome. We emphasize the severity and the difficulties in the management of renal complications that could be limiting the survival of these patients.
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http://dx.doi.org/10.1016/j.urology.2012.10.035DOI Listing
February 2013

The imaging and pathological features of a mucinous tubular and spindle cell carcinoma of the kidney: a case report.

World J Surg Oncol 2013 Feb 2;11:34. Epub 2013 Feb 2.

Department of Pathology - Faculdade de Medicina Ribeiro Preto, University of Sao Paulo, Ribeirao Preto, State of Sao Paulo, Brazil.

A mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and recently described kidney neoplasm with distal nephron differentiation. It can affect patients of all ages and is more prevalent among women. In this case report, we present a 50-year-old woman who had a renal mass, which was accidently discovered during an investigation for chronic anemia. The final diagnosis of MTSCC was made after the lesion was removed and a pathology work-up was performed. The clinical, pathological and imaging findings of this rare neoplasm are described in this report.
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http://dx.doi.org/10.1186/1477-7819-11-34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566951PMC
February 2013

Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome?

Ultrasound Med Biol 2012 Oct 21;38(10):1689-94. Epub 2012 Aug 21.

Department of Internal Medicine (Imaging Science Center), School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil.

The aim of this study was to evaluate the prognostic implications of the sonographic appearance of prostate cancers. All patients with biopsy-proven prostate cancer between January 2003 and July 2004 (and at least 5 years of follow-up) were selected retrospectively. After exclusions, 101 patients constituted our study population and were divided into isoechoic (or nonvisible) and hypoechoic (or visible) lesion. The clinical outcomes of these two groups were compared. The outcomes for the two groups were significantly different (p < 0.01). For nonvisible lesions, 37 of the 41 patients (90.2%) had no disease relapse and 2 (4.9%) had biochemical failure. For the visible lesions, 37 of the 60 (61.6%) patients were free of recurrence, 7 (11.7%) had systemic metastases and 10 (16.7%) died of complications related to prostate cancer. Our data show that patients with nonvisible prostate cancer had significantly better outcomes than patients with visible lesions during a five-year period of evaluation.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.06.006DOI Listing
October 2012

Expression profile of apoptosis-related genes in childhood adrenocortical tumors: low level of expression of BCL2 and TNF genes suggests a poor prognosis.

Eur J Endocrinol 2012 Aug 22;167(2):199-208. Epub 2012 May 22.

Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.

Background: Impaired apoptosis has been implicated in the development of childhood adrenocortical tumors (ACT), although the expression of apoptosis-related gene expression in such tumors has not been reported.

Methods: The mRNA expression levels of the genes CASP3, CASP8, CASP9, FAS, TNF, NFKB, and BCL2 were analyzed by quantitative real-time PCR in consecutive tumor samples obtained at diagnosis from 60 children with a diagnosis of ACT and in 11 non-neoplastic adrenal samples. BCL2 and TNF protein expression was analyzed by immunohistochemistry.

Results: A significant association was observed between tumor size ≥100 g and lower expression levels of the BCL2 (P=0.03) and TNF (P=0.05) genes; between stage IV and lower expression levels of CASP3 (P=0.008), CASP9 (P=0.02), BCL2 (P=0.002), TNF (P=0.05), and NFKB (P=0.03); Weiss score ≥3 and lower expression of TNF (P=0.01); unfavorable event and higher expression values of CASP9 (P=0.01) and lower values of TNF (P=0.02); and death and lower expression of BCL2 (P=0.04). Underexpression of TNF was associated with lower event-free survival in uni- and multivariate analyses (P<0.01). Similar results were observed when patients with Weiss score <3 were excluded.

Conclusion: This study supports the participation of apoptosis-related genes in the biology and prognosis of childhood ACT and suggests the complex role of these genes in the pathogenesis of this tumor.
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http://dx.doi.org/10.1530/EJE-12-0183DOI Listing
August 2012

Chronic partial urethral obstruction in female rats: description of an experimental model and initial results.

Acta Cir Bras 2011 ;26 Suppl 2:111-4

Department of Surgery and Anatomy, FMRP, USP, Ribeirao Preto-SP,

Purpose: To develop an experimental model of infravesical urinary obstruction in female rats.

Methods: After median caudal laparotomy, the urethra of 14 female rats was delicately separated from the vagina and loosely wrapped with cellophane tape measuring 0.4 x 1.0 cm. The animals were evaluated 4 (n=7) and 8 (n=7) weeks later. Five additional control animals were only subjected to separation of the urethra and vagina and monitored for 12 weeks.

Results: After four weeks, three rats presented vesical dilation associated with discrete ureteral ectasis in 2 animals, with the third presenting discrete hydronephrosis in one kidney. After eight weeks, five rats (71.4%) presented vesical distension with bilateral ureterohydronephrosis. No significant changes (p>0.05) in serum urea or creatinine occurred in any group compared to preoperative values.

Conclusion: We present here an inexpensive and simple method for the slow induction of urethral obstruction in adult female rats, with the development of progressive vesical hypertrophy and ureterohydronephrosis, which may be used as an experimental model for the study of different aspects of obstructive nephropathy.
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http://dx.doi.org/10.1590/s0102-86502011000800020DOI Listing
June 2012

Abdominal compartment syndrome caused by massive pyonephrosis in an infant with primary obstructive megaureter.

Case Rep Med 2011 31;2011:174167. Epub 2011 Jul 31.

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Avenida dos Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.

The authors report a case of abdominal compartment syndrome caused by massive pyonephrosis in an infant with primary obstructive megaureter successfully treated with emergency surgical decompression.
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http://dx.doi.org/10.1155/2011/174167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3147139PMC
November 2011

Using Mitrofanoff's principle and Monti's technique as a surgical option for bladder augmentation with a continent stoma: a case report.

J Med Case Rep 2011 Feb 3;5:49. Epub 2011 Feb 3.

Department of Surgery and Anatomy, Division of Urology, Ribeirao Preto Medical School, Sao Paulo University, Sao Paulo, Brazil.

Introduction: Hydronephrosis, reflux and renal failure are serious complications that occur in patients with neurogenic bladder associated with myelomeningocele. When the bladder compliance is lost, it is imperative to carry out surgery aimed at reducing bladder storage pressure. An ileocystoplasty, and for patients not suitable for intermittent catheterization, using the Mitrofanoff principle to form a continent stoma and the subsequent closure of the bladder neck, can be used. We report here, for the first time to the best of our knowledge, an association between two previously described techniques (the Mitrofanoff principle and the technique of Monti), that can solve the problem of a short appendix in obese patients.

Case Presentation: A 33-year-old male Caucasian patient with myelomeningocele and neurogenic bladder developed low bladder compliance (4.0 mL/cm H2O) while still maintaining normal renal function. A bladder augmentation (ileocystoplasty) with continent derivation principle (Mitrofanoff) was performed. During surgery, we found that the patient's appendix was too short and was insufficient to reach the skin. We decided to make an association between the Mitrofanoff conduit and the ileal technique of Monti, through which we performed an anastomosis of the distal stump of the appendix to the bladder (with an antireflux valve). Later, the proximal stump of the appendix was anastomosed to an ileal segment of 2.0 cm that was open longitudinally and reconfigured transversally (Monti technique), modeled by a 12-Fr urethral catheter, and finally, the distal stump was sutured at the patient's navel.After the procedure, a suprapubic cystostomy (22 Fr) and a Foley catheter (10 Fr) through the continent conduit were left in place. The patient had recovered well and was discharged on the tenth day after surgery. He remained with the Foley catheter (through the conduit) for 21 days and cystostomy for 30 days. Six months after surgery he was continent with good bladder compliance without reflux and fully adapted to catheterization through the navel.

Conclusion: The unpublished association between the Mitrofanoff and Monti techniques is feasible and a very useful alternative in urologic cases of derivation continent in which the ileocecal appendix is too short to reach the skin (i.e., in obese patients).
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http://dx.doi.org/10.1186/1752-1947-5-49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038960PMC
February 2011

Histologic study of urethral extracellular matrix and collagen from aging and long-term alloxan-induced diabetic male rats.

Urology 2011 Feb 13;77(2):510.e6-11. Epub 2010 Dec 13.

Department of Anatomy and Surgery, University of São Paulo Faculty of Medicine of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.

Objectives: To evaluate the histological alterations of extracellular matrix in long-term alloxan-induced diabetes and aging urethras of male rats with descriptions of total connective tissue, muscle layer and collagen types I and III relative amounts.

Methods: Histologic evaluations were performed in 3 animal groups: group 1, 8 weeks old; group 2, 44 weeks old; and group 3, 44 weeks old with alloxan-induced diabetes. The muscle layer thickness, extracellular matrix fibrosis, and collagen were quantified on digital images of the urethral samples.

Results: A higher total thickness and muscle layer thickness and higher connective tissue and collagen content were observed in the urethras of group 3. No changes in the collagen type III/I ratio were found in the urethra of groups 2 and 3.

Conclusions: Our results suggest that the morphologic alterations of the urethra should also be considered in long-term studies of diabetic lower urinary tract dysfunction. These morphologic alterations due to diabetes differ from the changes induced by aging itself and could represent a final stage in decompensate urethras. Further studies are necessary to establish the real influence of the urethral morphologic changes on lower urinary tract diabetes dysfunction.
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http://dx.doi.org/10.1016/j.urology.2010.09.033DOI Listing
February 2011

Chronic alcoholism associated with diabetes impairs erectile function in rats.

BJU Int 2010 Jun 2;105(11):1592-7. Epub 2010 Feb 2.

Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Brazil.

Objective: To investigate the effects of chronic ethanol consumption and diabetes on nitric oxide (NO)-mediated relaxation of cavernosal smooth muscle (CSM).

Material And Methods: Male Wistar rats were divided into four groups: control, isocaloric, diabetic and ethanol-diabetic. The CSMs were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (ACh; 0.01-1000 micromol/L), sodium nitroprusside (SNP, 0.01-1000 micromol/L) or EFS (1-32 Hz) in strips pre-contracted with phenylephrine (10 micromol/L). Immunoexpression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was also accessed.

Results: The endothelium-dependent relaxation induced by ACh was decreased in CSM from ethanol-diabetic rats when compared with the controls, with a mean (sem) of 21 (4) vs 37 (2)%. Similarly, the potency and maximal responses induced by SNP were reduced in the ethanol-diabetic [3.97 (0.38) and 85 (1)%, respectively] and diabetic groups [3.78 (0.56) and 81 (2)%, respectively] when compared with the controls [5.3 (0.22) and 90 (3)%, respectively] and isocaloric [5.3 (0.19) and 92 (1)%, respectively] groups. Noradrenergic nerve-mediated contractions of CSM in response to EFS were increased in rats from ethanol-diabetic and diabetic groups when compared with the control and isocaloric groups. Conversely, there were no differences in EFS-induced relaxation among the groups. The immunostaining assays showed overexpression of eNOS and iNOS in the CSM from diabetic and ethanol-diabetic rats when compared with the control and isocaloric rats.

Conclusion: There was an impairment of relaxation of CSM from ethanol-diabetic and diabetic rats that involved a decrease in the NO-cyclic guanosine monophosphate signalling pathway by endothelium-dependent mechanisms accompanied by a change in the CSM contractile sensitivity.
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http://dx.doi.org/10.1111/j.1464-410X.2009.09084.xDOI Listing
June 2010

Chronic ethanol consumption induces cavernosal smooth muscle dysfunction in rats.

Urology 2009 Dec 16;74(6):1250-6. Epub 2009 Jul 16.

Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.

Objectives: To investigate the effects of chronic ethanol consumption on nitric oxide (NO)-mediated relaxation in rat cavernosal smooth muscle (CSM).

Methods: Male wistar rats were divided into 2 groups: control and ethanol. CSM obtained from both groups were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hertz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (0.01-1000 micromol L(-1)), sodium nitroprusside (SNP, 0.01-1000 micromol L(-1)), or EFS (1-32 Hz) in strips precontracted with phenylephrine (10 micromol L(-1)). Blood ethanol, serum testosterone levels, and basal nitrate generation were determined. Immunoexpression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was also accessed.

Results: Ethanol intake for 4 weeks significantly increased noradrenergic nerve-mediated contractions of CSM in response to EFS. The endothelium-dependent relaxation induced by acetylcholine decreased after the ethanol treatment. Ethanol consumption decreased serum testosterone levels but did not affect the nitrate levels on rat CSM. The mRNA and protein levels for eNOS and iNOS receptors were increased in CSM from ethanol-treated rats.

Conclusions: Ethanol consumption reduces endothelium-dependent relaxation induced by acetylcholine, but does not affect SNP or EFS-induced relaxation, suggesting that ethanol disrupts the endothelial function. Despite the overexpression of eNOS and iNOS in ethanol-treated rats, the impaired relaxation induced by acetylcholine may suggest that chronic ethanol consumption induces endothelial dysfunction.
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http://dx.doi.org/10.1016/j.urology.2009.04.043DOI Listing
December 2009