Entity

Time filter

Source Type

Porto Alegre, Brazil

Santos T.,University of Porto | Drummond M.,University of Porto | Botelho F.,Servico de Urologia
Revista Portuguesa de Pneumologia | Year: 2012

Introduction: OSAS (obstructive sleep apnea syndrome) is defined by recurrent episodes of upper airway obstruction during sleep, causing multiple clinical consequences. Literature review suggests that OSAS induces a spectrum of abnormalities in neural, hormonal and vascular regulation that contribute to the development of ED (erectile dysfunction). The aims of this study were to estimate the prevalence of ED in OSAS patients and evaluate its determinants. Methods: 62 patients from Hospital S. João Sleep Laboratory with newly diagnosed OSAS were included in the study and answered the IIEF-5 (international index erectile function 5 item version) questionnaire. Results: The prevalence of ED in OSAS patients was 64.4%. Age and diabetes constituted themselves as independent risk factors for more severe degrees of ED: OR = 1.226 (95% CI: 1.062---1.415) and OR = 31.205 (95% CI: 1.222---796.557), respectively. Compared with nonsmokers, ex-smokers group revealed a positive association with ED: OR = 4.32 (95% CI: 1.09---17.11). Hypertension and ACEI (angiotensin converting enzyme inhibitors) or ARB (angiotensin II receptor blockers) therapy were also correlated to ED symptoms: OR = 3.25 (95% CI: 1.09---9.65) and 7.39 (95% CI: 1.52---35.99), respectively. No association was found relating BMI (p = 0.254), alcoholic habits (p = 0.357), acute myocardial infarction (p = 0.315), dyslipidemia (p = 0.239), metabolic syndrome (p = 0.215) and ED. OSAS severity was not associated with ED in our sample. Conclusions: The prevalence of ED in OSAS patients is high. ED determinants in our sample were age and diabetes. Past smoking habits, hypertension and ACEI/ARB therapy also revealed a statistically significant association with ED. 2011 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L. All rights reserved.


Matos A.R.,Programa Of Pos Graduacao Stricto Sensu Em Oncologia Do Instituto Nacional Of Cancer Inca | Coutinho-Camillo C.M.,Hospital AC Camargo | Thuler L.C.S.,Coordenacao de Pesquisa Clinica INCA | Thuler L.C.S.,Rio de Janeiro State Federal University | And 5 more authors.
Experimental and Molecular Pathology | Year: 2013

Thrombospondin 2 (TSP2) is a protein with important roles in different tumor types, mainly related to tumor inhibition. However, there are limiting data regarding TSP2 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH). We aimed to investigate TSP2 transcript and protein expression in tumoral and non-tumoral prostate tissues and cell lines, and its implications for PCa diagnosis and progression. TSP2 transcript expression was evaluated by real time PCR in PCa and BPH tissue samples and in tumoral and non-tumoral cell lines. TSP2 protein expression analysis was conducted by immunohistochemistry in a tissue microarray (TMA) containing PCa and BPH tissue samples. TSP2 transcript was down-regulated in PCa tissue samples and cell lines, when compared to BPH and non-tumoral samples (P < 0.01). Receiver Operating Curve (ROC) analysis demonstrated that TSP2 transcript levels can better distinguish PCa from BPH tissue samples (P < 0.01) than serum PSA levels (P = 0.299). TSP2 protein expression has been observed in the cytoplasm of both PCa and BPH epithelial and stromal compartments. TSP2 stromal staining scores were significantly lower in PCa than in BPH tissues (P < 0.01), while similar TSP2 epithelial staining patterns were observed in both diseases. Notably, the TSP2 epithelial staining score was significantly correlated to vascular invasion and biochemical recurrence in PCa tissue samples (P < 0.05). Our data indicate that TSP2 is down-regulated at PCa tissues and cell lines, especially at stroma compartment, which could be related to PCa progression. TSP2 levels could potentially be applied for differential PCa and BPH diagnosis. © 2013 Elsevier Inc.


Angulo J.,Hospital Ramon y Cajal | Gonzalez-Corrochano R.,Hospital Ramon y Cajal | Cuevas P.,Hospital Ramon y Cajal | Fernandez A.,Hospital Ramon y Cajal | And 4 more authors.
Journal of Sexual Medicine | Year: 2010

Introduction.: Diabetic men with erectile dysfunction (ED) are less responsive to therapy with type 5 phosphodiesterase (PDE5) inhibitors. Although an impairment of the nitric oxide (NO)/cyclic guanosin-monophosphate (cGMP) pathway has been shown in diabetic ED vs. non-diabetic ED, the functionality of NO/cGMP pathway in non-diabetic and diabetic ED patients with respect to non-ED patients has not been established. Aim.: The aim of this study is to evaluate the function of NO/cGMP signalling in human erectile tissues from ED patients exploring the added impact of diabetes. Methods.: Corpus cavernosum strips (human corpus cavernosum [HCC]) and penile resistance arteries (HPRA) were collected from penile specimens from organ donors (OD) and from diabetic and non-diabetic men with ED undergoing penile prosthesis implantation. Main Outcome Measures.: Relaxations to acetylcholine, electrical field stimulation, sodium nitroprusside, and sildenafil were evaluated in phenylephrine-contracted HCC and norepinephrine-contracted HPRA. cGMP content in HCC was also determined. Results.: The impairment of endothelium-dependent relaxation in HCC and HPRA from ED patients was exacerbated by diabetes (Emax 76.1, 62.9, and 49.3% in HCC and 73.1, 59.8, and 46.0% in HPRA from OD, non-diabetic and diabetic ED, respectively). Hypertension, hypercholesterolemia, or aging did not exert a further impairment of endothelial relaxation among ED patients. Diabetes also causes a further impairment of neurogenic relaxation in HCC and HPRA. The basal and stimulated content of cGMP in HCC was significantly decreased in patients with ED, but specially reduced in diabetic patients. Diabetes clearly impaired PDE5 inhibitor-induced vasodilation of HPRA from ED patients. Conclusions.: ED is related to impaired vasodilation, reduced relaxant capacity, and diminished cGMP content in penile tissue. These alterations are more severe in diabetes and accompany reduced relaxant efficacy of PDE5 inhibition. Thus, an exacerbated reduction of nitric oxide/cGMP signaling could be responsible for ED in diabetic men and would explain their reduced response to treatment. © 2009 International Society for Sexual Medicine.


Angulo J.,Hospital Universitario Ramon y Cajal | Cuevas P.,Hospital Universitario Ramon y Cajal | Fernandez A.,Hospital Universitario Ramon y Cajal | La Fuente J.M.,Servico de Urologia | And 3 more authors.
Journal of Sexual Medicine | Year: 2012

Introduction. Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTSs) may be associated with erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors used for treating ED have shown clinical benefit in patients with LUTS but their actions in human LUT tissues are not well defined. Aim. To determine the effects of the long-acting PDE5 inhibitor, tadalafil, on smooth muscle tone in human prostate and bladder neck as well as to evaluate the influence of tadalafil on the efficacy of the α-adrenergic receptor antagonist, tamsulosin, in inhibiting contractile responses in these tissues. Methods. Strips of human peripheral prostate (HPP), human internal prostate (HIP), and human bladder neck (HBN) were obtained from organ donors and patients with BPH. The strips were then disposed in organ baths to evaluate nitric oxide/cyclic guanosine monophosphate (cGMP)-mediated relaxation and cGMP kinetics in HPP and HIP, and electrical field stimulation (EFS)-induced neurogenic contractions in HPP and HBN. Main Outcome Measures. Tadalafil-induced effects on sodium nitroprusside (SNP)-induced relaxation and cGMP accumulation in HPP and HIP and influence of tadalafil and tamsulosin on EFS-induced contractions of HPP and HBN. Results. SNP-induced relaxation of HPP and HIP was significantly potentiated by tadalafil (30-60nM). SNP-induced cGMP accumulation in HPP and HIP was enhanced by tadalafil (30-60nM), but significant difference was only obtained in HPP. EFS-induced contractions sensitive to tetrodotoxin in HPP were significantly inhibited by tadalafil (30nM) but not by tamsulosin (0.01-100nM) or vehicle. Further inhibition of neurogenic responses in HPP was achieved by combining tadalafil and tamsulosin treatments. Tamsulosin, but not tadalafil, significantly reduced EFS-induced contractions in HBN, but the coadministration of both therapies resulted in additional inhibition of contractions. Conclusions. While tadalafil enhances cGMP accumulation and potentiates prostate relaxation, tadalafil combined with tamsulosin results in enhanced inhibition of neurogenic contractions of HPP and HBN. © 2012 International Society for Sexual Medicine.


La Fuente J.M.,Servico de Urologia | Fernandez A.,Hospital Universitario Ramon y Cajal | Cuevas P.,Hospital Universitario Ramon y Cajal | Gonzalez-Corrochano R.,CSIC - Biological Research Center | And 2 more authors.
European Journal of Pharmacology | Year: 2014

We have analysed the effects of large-conductance calcium-activated potassium channel (BK) stimulation on neurogenic and myogenic contraction of human bladder from healthy subjects and patients with urinary symptoms and evaluated the efficacy of activating BK to relief bladder hyperactivity in rats. Bladder specimens were obtained from organ donors and from men with benign prostatic hyperplasia (BPH). Contractions elicited by electrical field stimulation (EFS) and carbachol (CCh) were evaluated in isolated bladder strips. in vivo cystometric recordings were obtained in anesthetized rats under control and acetic acid-induced hyperactive conditions. Neurogenic contractions of human bladder were potentiated by blockade of BK and small-conductance calcium-activated potassium channels (SK) but were unaffected by the blockade of intermediate calcium-activated potassium channels (IK). EFS-induced contractions were inhibited by BK stimulation with NS-8 or NS1619 or by SK/IK stimulation with NS309 (3 μM). CCh-induced contractions were not modified by blockade or stimulation of BK, IK or SK. The anti-cholinergic agent, oxybutynin (0.3 μM) inhibited either neurogenic or CCh-induced contractions. Neurogenic contractions of bladders from BPH patients were less sensitive to BK inhibition and more sensitive to BK activation than healthy bladders. The BK activator, NS-8 (5 mg/kg; i.v.), reversed bladder hyperactivity induced by acetic acid in rats, while oxybutynin was ineffective. NS-8 did not significantly impact blood pressure or heart rate. BK stimulation specifically inhibits neurogenic contractions in patients with urinary symptoms and relieves bladder hyperactivity in vivo without compromising bladder contractile capacity or cardiovascular safety, supporting its potential therapeutic use for relieving bladder overactivity. © 2014 Elsevier B.V.

Discover hidden collaborations