Publications by authors named "Carlos Augusto Fernandes Molina"

12 Publications

  • Page 1 of 1

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

Prevalence of Vas Deferens Calcifications on Abdominal CT Examinations and Association With Systemic Conditions.

AJR Am J Roentgenol 2020 12 6;215(6):1398-1402. Epub 2020 Oct 6.

Department Medical Images, Radiation Therapy, and Oncohematology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.

The purpose of this study was to describe the prevalence of vas deferens (VD) calcifications on abdominal CT examinations and the associations between VD calcifications and several systemic conditions. The CT examinations of male patients from January 2010 to December 2011 were retrospectively reviewed. After exclusions, the records of 1915 consecutively identified patients were analyzed. Five readers, 3rd- and 4th-year radiology residents, recorded the presence and laterality of VD calcifications and of vascular calcifications presumed due to atherosclerosis. A sixth reader parsed the patient records for diagnoses of type 2 diabetes mellitus (DM) and chronic kidney disease (CKD). The mean age of the entire sample population was 52.9 ± 18.9 years (range, 1-93 years). The mean age of patients with VD calcifications was 59.3 ± 12.0 (SD) years and of the group without VD calcifications was 52.9 ± 19.1 years ( = 0.17). The prevalence of VD calcification was 1.61% (31 patients): 21 (67.7%) of the patients had bilateral calcification; seven (22.6%), right-sided only; and three, (9.7%) left-sided. The frequency of DM was 28.8% (551/1915), of CKD was 7.58% (150/1915), and of atherosclerosis, 60.4% (1156/1915). The mean caliber of calcified VDs was 5.31 ± 1.29 mm versus 3.63 ± 0.63 mm for patients without calcification or any chronic condition ( < 0.0001). Among age, atherosclerosis, DM, and CKD in univariate regression analysis, only DM was associated with VD calcification ( = 0.006). However, because age ( = 0.063) and atherosclerosis ( = 0.057) were close to significant, they were included in the multivariate analysis, which also showed only DM associated with VD calcification (odds ratio, 2.14 ± 0.85). In the large cohort in this study, the prevalence of VD calcification was 1.61%. VD calcification was strongly associated with DM. The pathologic implications of VD calcification remain unclear and warrant further investigation in prospective longitudinal studies.
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http://dx.doi.org/10.2214/AJR.19.22672DOI Listing
December 2020

Chronic alcoholism associated with diabetes induced apoptosis in the corpus cavernosum of rats.

Acta Cir Bras 2020 Sep 7;35(8):e202000805. Epub 2020 Sep 7.

PhD, Associate Professor, Department of Surgery and Anatomy, FMRP-USP, Ribeirao Preto-SP, Brazil. Conception and design of the study, critical revision, supervised all phases.

Purpose: To evaluate the effects of alcohol exposure and diabetes on apoptotic process in the corpus cavernosum.

Methods: Forty eight male Wistar rats were divided into four groups: control, diabetic, alcoholic and diabetic-alcoholic. Samples of the corpus cavernosum were prepared to study protein expression of apoptotic genes (Caspases-3 and 9) by immunohistochemistry and Real-Time PCR.

Results: The immunoreactivity of Caspases-3 and -9 was diffuse and higher in the treated groups though there was no significant difference between the experimental groups, only when compared with the control group. An increase was observed in the gene expression of Caspases-9 in the diabetic and ethanol-diabetic groups when compared with control and ethanol groups.

Conclusions: The association of these factors (ethanol and diabetes) probably can affect the apoptosis mechanism in lesions of the cavernous tissue in the rat penis. Both gene and protein expression of Caspase-9 in diabetic and ethanol-diabetic groups suggest the involvement of the apoptosis cascade from this study model.
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http://dx.doi.org/10.1590/s0102-865020200080000005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478468PMC
September 2020

Morphological and molecular analysis of apoptosis in the corpus cavernosum of rats submitted to a chronic alcoholism model.

Acta Cir Bras 2020 3;35(3):e202000305. Epub 2020 Jun 3.

PhD, Associate Professor, Department of Surgery and Anatomy, FMRP-USP, Ribeirao Preto-SP, Brazil. Final approval.

Purpose: To evaluate the effect of chronic alcoholism on morphometry and apoptosis mechanism and correlate with miRNA-21 expression in the corpus cavernosum of rats.

Methods: Twenty-four rats were divided into two experimental groups: Control (C) and Alcoholic group (A). After two weeks of an adaptive phase, rats from group A received only ethanol solution (20%) during 7 weeks. The morphometric and caspase-3 immunohistochemistry analysis were performed in the corpus cavernosum. The miRNA-21 expression was analyzed in blood and cavernous tissue.

Results: Chronic ethanol consumption decreased cavernosal smooth muscle area of alcoholic rats. The protein expression of caspase 3 in the corpus cavernosum was higher in A compared to the C group. There was no difference in the expression of miRNA-21 in serum and cavernous tissue between the groups.

Conclusion: Chronic ethanol consumption reduced smooth muscle area and increased caspase 3 in the corpus cavernosum of rats, without altered serum and cavernosal miR-21 gene expression.
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http://dx.doi.org/10.1590/s0102-865020200030000005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282493PMC
June 2020

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

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

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

Complications after bladder augmentation in children.

Acta Cir Bras 2016 ;31 Suppl 1:8-12

Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Brazil.

Purpose: Bladder augmentation is an effective surgical procedure for increasing bladder capacity and reducing pressure on the urinary system. It is indicated for patients with anomalies such as spina bifida, myelomeningocele, urethral valve and bladder exstrophy, who progress with low tolerance of medication.

Cases: This was a retrospective study conducted on pediatric patients submitted to bladder augmentation from 2000 to 2011.

Results: 34 patients aged 4 to 17 years were submitted to bladder augmentation, 30 of them with an ileal loop and 4 with a ureter.A continent urinary shunt was performed in 16 patients, the Mitrofanoff conduit was associated in 15, and the Macedo technique was used in one. Mean follow-up was 34.35 months (1 to 122 months). Mean creatinine was 1.5 ng/ml (0.4 to 7.5 ng/ml) preoperatively and 1.78 ng/ml postoperatively. Three patients required a renal transplant during follow-up. There was improvement or resolution of vesicoureteral reflux in 83.5% of the kidneys on the right and in 75% on the left. Bladder capacity increased, on average, from 152.5 ml to 410 ml. The main complications were vesical lithiasis in 3 patients and conduit perforation in one.

Conclusion: Bladder augmentation showed good results in this series, preserving renal function in most of the patients.
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http://dx.doi.org/10.1590/S0102-86502016001300003DOI Listing
May 2017

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

Expression of VEGF and collagen using a latex biomembrane as bladder replacement in rabbits.

Int Braz J Urol 2012 Jul-Aug;38(4):536-43

Department of Surgery, Division of Urology, Ribeirão Preto Medical School - University of Sao Paulo Ribeirão Preto, SP and Department of Experimental Surgery, Anhanguera-Uniderp University, Campo Grande, MS, Brazil.

Objective: To investigate the VEGF expression and collagen deposition using a latex biomembrane as bladder replacement in rabbits.

Materials And Methods: After partial cystectomy, a patch of a non-vulcanized latex biomembrane (2 x 2 cm) was sewn to the bladder of rabbits with 5/0 monofilament polydioxanone sulfate sutures in a watertight manner. Groups of 5 animals were killed at 15, 45 and 90 days after surgery and the bladder was removed. Sections of 5µm were cut and stained with picrosirius-red in order to estimate the amount of extracellular matrix in the graft. To confirm the presence of VEGF in tissues, protein expression was determined by immunohistochemistry.

Results: No death, urinary leakage or graft extrusion occurred in any group. All bladders showed a spherical shape. A progressive reduction in the amount of collagen occurred in the graft area and was negatively and linearly correlated with time (p < 0.001). VEGF expression was higher in grafted areas when compared to controls at 15 and 45 days after surgery and decreased with time (p < 0.001).

Conclusion: The latex biomembrane as a matrix for partial bladder replacement in rabbits promotes temporary collagen deposition and stimulates the angiogenic process.
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http://dx.doi.org/10.1590/s1677-55382012000400014DOI Listing
May 2013

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats.

Acta Cir Bras 2012 Jul;27(7):477-81

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

Purpose: To investigate the effect of lovastatin on renal ischemia followed by reperfusion.

Methods: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated.

Results: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B.

Conclusions: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.
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http://dx.doi.org/10.1590/s0102-86502012000700008DOI Listing
July 2012

Compensatory renal growth and mitochondrial function: the influence of warm ischemia and reperfusion.

Acta Cir Bras 2008 ;23 Suppl 1:31-5; discussion 35

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

Purpose: To evaluate the influence of ischemia/reperfusion injury on renal compensatory growth (CGR) and mitochondrial function.

Methods: Forty five Wistar rats were divided in 3 groups: Control Group (GC) - 21 rats were submitted to a sham laparotomy and sacrificed at 1st (6 rats) and 7th (15 rats) postoperative days to evaluate the dry weight of both kidneys and their growth during 1 week (6 rats) and to quantify mitochondrial respiration (9 rats); Group 1 (G1) - 12 rats underwent right nephrectomy and were sacrificed 7 days later for analysis of renal mitochondrial function (6 rats) and dry weight (6 rats). Group 2 (G2) - renal warm ischemia for 60 minutes followed by right nephrectomy was performed in 12 rats; they were sacrificed 7 days later to evaluate renal mitochondrial function (6 rats) and dry weight (6 rats).

Results: Dry weight (mg) of left kidneys at 7th day: GC - 219+/-18, G1 - 281+/-23 and G2 - 338+/-39 (GCxG1 p<0.01; GCxG2 p<0.001; G1xG2 p<0.01). State 4 mitochondrial respiration rate and respiratory control ratio (RCR) were similar in all groups (p>0.05). State 3 respirations (mM/min/mg) in GC, G1 and G2 was respectively: 99+/-23, 132+/-22 and 82+/-44 (p<0.02; the only statistical difference noted was between groups G1xG2 - p<0.05).

Conclusions: Following unilateral nephrectomy CRG is associated with an increase in state 3 of mitochondrial respiration. Renal ischemia/reperfusion injury enhances the CRG provoked by unilateral nephrectomy but such enhancement seems independent on mitochondrial respiration.
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http://dx.doi.org/10.1590/s0102-86502008000700006DOI Listing
June 2009