Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia.

BACKGROUND/AIM: Periprostatic adipose tissue (PPAT) directs tumour behaviour. Microenvironment secretome provides information related to its biology. This study was performed to identify secreted proteins by PPAT, from both prostate cancer and benign prostate hyperplasia (BPH) patients. PATIENTS AND METHODS: Liquid chromatography-mass spectrometry-based proteomic analysis was performed in PPAT-conditioned media (CM) from patients with prostate cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or benign disease (CM-BPH). RESULTS: The highest number and diversity of proteins was identified in CM-T3. Locomotion was the biological process mainly associated to CMs-T and reproduction to CM-T3. Immune responses were enriched in CMs-T. Extracellular matrix and structural proteins were associated to CMs-T. CM-T3 was enriched in proteins with catalytic activity and CM-T2 in proteins with defense/immunity activity. Metabolism and energy pathways were enriched in CM-T3 and those with immune system functions in CMs-T. Transport proteins were enriched in CM-T2 and CM-BPH. CONCLUSION: Proteins and pathways reported in this study could be useful to distinguish stages of disease and may become targets for novel therapies.

Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction.

INTRODUCTION: Several cases of adulteration of dietary supplements with tadalafil, sildenafil, and vardenafil, or their unapproved analogues have been reported worldwide. Mainly, the presence of the latter represents a serious health risk to consumers as their efficacy and toxic effects have not been assessed and may result in unpredictable adverse effects. AIM: To investigate the suspected adulteration with synthetic phosphodiesterase type 5 (PDE-5) inhibitors in a dietary supplement marketed in Argentina for the treatment of erectile dysfunction (ED). METHODS: The content of the capsules of the dietary supplement (sample A) was analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) diode-array detection. From the organic extract of sample A, a major compound was purified by column chromatography (CC). The isolated compound was identified by proton nuclear magnetic resonance (1H NMR) and carbon NMR (13C NMR), heteronuclear single quantum coherence, distortionless enhancement by polarization transfer (DEPT 135), electrospray ionization mass spectrometry, and ultraviolet, and infrared (Fourier transform infrared spectroscopy) spectroscopy. MAIN OUTCOME MEASURE: Proof of adulteration of herbal products with synthetic PDE-5 inhibitors. RESULTS: By TLC and HPLC analysis, a major compound was detected in sample A organic extract. The purification of this extract by CC led to the isolation of a pure compound which was identified according to its spectral data as (6R,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino [1',2':1,6] pyrido [3,4-b] indole-1,4-dione or aminotadalafil. CONCLUSIONS: An unapproved PDE-5 inhibitor analogue, which was identified as aminotadalafil, has been detected in a dietary supplement. This study represents the first report in Latin America and one of the few independent studies of an adulteration with an unapproved PDE-5 inhibitor of an herbal product for ED treatment.

Human periprostatic adipose tissue: its influence on prostate cancer cells.

BACKGROUND/AIMS: Adipose microenvironment is involved in signaling pathways that influence prostate cancer (PCa) progression. However, the role of human periprostatic adipose tissue (PPAT) from patients with benign prostatic hyperplasia (BPH) has not been studied and compared to that of PPAT from PCa patients. The aim of this paper was to investigate the influence of factors derived from both PPATs on the behavior of androgen-dependent and castration resistant PCa cells. METHODS: PPAT conditioned media (CM) were obtained from tissue samples from patients with clinically primary PCa (TPPAT) or BPH (BPPAT). Cell adhesion, proliferation, migration and metalloproteinase expression were evaluated following exposure of LNCaP (androgen dependent) and PC3 (androgen independent) prostate cancer cell lines to BPPAT or TPPAT CM. RESULTS: Proliferation or motility of LNCaP or PC3 cells were not significantly affected by TPPAT or BPPAT CM. The number of LNCaP but not PC3 cells attached to components of TPPAT CM significantly decreased compared to cells attached to BPPAT CM. PPAT produced and released pro-MMP-9. Zymograms demonstrated that TPPAT CM induced a significant increase in pro-MMP-9 activity compared to BPPAT CM in LNCaP cells but not in PC3 cells. CONCLUSIONS: We conclude that TPPAT released factors, such as pro-MMP-9, could induce the invasive capacity of LNCaP cells and speculate that PPAT derived factors could, in the early stages of prostate cancer, modulate disease progression.

In vivo and in vitro effects of nebivolol on penile structures in hypertensive rats.

BACKGROUND: Erectile dysfunction is associated with high blood pressure and antihypertensive treatment, especially diuretics and traditional beta-blockers. Nevertheless, new beta-blockers such as nebivolol present some differences with respect to the classic beta-blockers. The aim of this study was to determine the functional and morphologic effects of nebivolol on penile structures in hypertensive rats. METHODS: During a 6-month period, male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rats were studied. The groups were as follows: 1) untreated SHR (Untreated-SHR); 2) SHR given nebivolol 10 mg/kg/day (SHR+N); 3) SHR given amlodipine 3 mg/kg/day (SHR+AML); and 4) untreated WKY (untreated-WKY). Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, as well as collagen type III (COL III) in cavernous tissue, were evaluated. RESULTS: After 6 months, SHR groups given nebivolol and amlodipine showed similar reductions in blood pressure compared with untreated SHR. However, only SHR+N and control WKY showed significantly lower values of CSM (P < 01), VSM (P < 01), and COL III (P < 01) when compared with untreated SHR and SHR+AML. In addition SHR+N showed a higher endothelial nitric oxide synthase expression in sinusoidal endothelium compared with SHR, and SHR+AML (P < 01). In vitro studies revealed that SHR+N displayed a better relaxation response to acetylcholine than untreated-SHR and SHR+AML (P < 01). CONCLUSION: Nebivolol presented equivalent BP control compared with amlodipine. However, only nebivolol showed a significant better functional outcome with a protective role against structural changes in erectile tissue that are caused by arterial hypertension.

Differences between Candesartan and Hydralazine in the protection of penile structures in spontaneously hypertensive rats.

INTRODUCTION: Previous studies indicate that angiotensin type I receptor antagonists present a beneficial effect on penile structures in hypertensive rats. However, at present there is no substantial information concerning the functional aspect of this class of antihypertensive drugs. AIM: To determine, by in vitro studies, functional effects of Candesartan in comparison with a traditional vasodilating agent, Hydralazine, on penile structures in a rat model of arterial hypertension. METHODS: During 4 months, three groups of male spontaneously hypertensive rats (SHR) and one of Wistar-Kyoto (WKY) rats, as control group, were studied: SHR without treatment; SHR with Candesartan cilexetil 7.5 mg/kg/day; SHR with Hydralazine 50 mg/kg/day; and WKY rats without treatment. Cavernous smooth muscle strips were mounted in an organ bath system for in vitro studies. In addition, cavernous smooth muscle and vascular smooth muscle from cavernous arteries, cavernous tissue fibrosis, and collagen type III were also evaluated by immunohistochemistry. RESULTS: After 4 months, SHR with Candesartan and Hydralazine showed similar reduction in blood pressure compared with untreated SHR. However, in vitro studies revealed that SHR with Candesartan displayed a better relaxation response to acetylcholine than SHR and SHR with Hydralazine (P < 0.01). Immunostaining indicates that only SHR with Candesartan and control WKY rats showed significantly lower values of: (i) cavernous smooth muscle (P < 0.01); (ii) vascular smooth muscle (P < 0.01); and (iii) collagen type III (P < 0.01) when compared with untreated SHR or SHR with Hydralazine. Additionally, SHR with Candesartan presented a higher endothelial nitric oxide synthase expression in sinusoidal endothelium in comparison with SHR, and SHR with Hydralazine (P < 0.01). CONCLUSION: Candesartan presented equivalent blood pressure control compared with Hydralazine. However, only Candesartan showed a significant better response to acetylcholine, in in vitro studies, with a protective role against structural changes in vessels as well as in cavernous spaces of the erectile tissue.

Different effect of losartan and amlodipine on penile structures in male spontaneously hypertensive rats.

BACKGROUND: Erectile dysfunction is highly prevalent in hypertensive patients. Since both angiotensin II receptor type-1 blockers (ARBs) and calcium antagonists are current and effective antihypertensive drugs, the aim of this study was to determine possible differences between ARBs and calcium antagonists concerning the protection of penile structures from the deleterious effects of arterial hypertension. METHODS AND RESULTS: During 6 months, 3 groups of male spontaneously hypertensive rats (SHR) and 1 of Wistar-Kyoto (WKY) rats, as a control group, were studied: SHR without treatment; SHR with losartan (L) 30 mg/kg/day; SHR with amlodipine (A) 3 mg/kg/day, and WKY without treatment. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, cavernous tissue fibrosis and collagen type III (COL III) were evaluated. After 6 months, SHR+L and SHR+A showed a similar reduction in blood pressure compared with untreated SHR. However, only SHR+L and control WKY presented significantly lower values of: CSM (p < 0.01), VSM (p < 0.01), and COL III (p < 0.01) when compared with either untreated SHR or SHR+A. There was also a positive correlation between left ventricular mass and proteinuria with VSM from cavernous arteries, CSM and COL III in untreated SHR and SHR+A. These relations were not present in SHR+L and WKY. CONCLUSION: Although losartan and amlodipine achieved similar blood pressure control, losartan but not amlodipine showed a significant protective role against structural changes in the vessels and cavernous spaces of the erectile tissue caused by arterial hypertension.

Tratamiento farmacológico de la disfunción eréctil / Farmacologic treatment of the erectile disfunction

Anatomía funcional del pene.- Mecanismos que regulan la erección.- Disfunción sexual eréctil: Etiología, diagnóstico, tratamiento.- Medicación oral; Aplicación transepitelial de drogas vasoactivas; Tratamiento hormonal; Fármacotest; Inyección intracavernosa: complicaciones.- Disfunción sexual eréctil orgánica y psicógena con erección farmacológica.- Disfunción sexual eréctil en la diabetes y el tabaquismo

Tratamiento farmacológico de la disfunción eréctil / Farmacologic treatment of the erectile disfunction

Anatomía funcional del pene.- Mecanismos que regulan la erección.- Disfunción sexual eréctil: Etiología, diagnóstico, tratamiento.- Medicación oral; Aplicación transepitelial de drogas vasoactivas; Tratamiento hormonal; Fármacotest; Inyección intracavernosa: complicaciones.- Disfunción sexual eréctil orgánica y psicógena con erección farmacológica.- Disfunción sexual eréctil en la diabetes y el tabaquismo

Plástica del muñon peneano en penectomias parciales / Plastic surgery of penis stumps in partial penectomy

Se presenta una técnica de cirugia plástica para la reconstrucción del glande en los muñones peneanos por amputación parcial oncológica. Se practicó con éxito en 7 pacientes que fueron seguidos por espacio de uno a cuatro años. Se utiliza un colgajo pediculado de escroto que en dos tiempos quirúrgicos, permite presentar un muñon peneano de aspecto normal y un neomeato con escasa tendencia a la estenosis

Valor diagnóstico del ultrasonido en patología tumoral de testículo / Diagnosis value of ultrasound in pathology testis tumors

Se presentan 19 pacientes con testiculos tumorales estudiados con ecografía (transductor de 5 MHz) y su correspondiente confirmación quirúrgica. La ecografía demostró una alta certeza diagnóstica: 96,8% para determinar la localización de una lesión escrotal (intratesticular, extratesticular o mixta). Frente a las lesiones neoplásicas, el método demostró alta sensibilidad: 100%, baja especificidad: 64%, y 85% de certeza diagnóstica. Se analizan en detalle los signos ultrasonográficos asociados a patología tumoral, así como el origen de los 5 falsos-positivos que disminuyen la especificidad ecográfica

Plástica del muñon peneano en penectomias parciales / Plastic surgery of penis stumps in partial penectomy

Se presenta una técnica de cirugia plástica para la reconstrucción del glande en los muñones peneanos por amputación parcial oncológica. Se practicó con éxito en 7 pacientes que fueron seguidos por espacio de uno a cuatro años. Se utiliza un colgajo pediculado de escroto que en dos tiempos quirúrgicos, permite presentar un muñon peneano de aspecto normal y un neomeato con escasa tendencia a la estenosis (AU)

Valor diagnóstico del ultrasonido en patología tumoral de testículo / Diagnosis value of ultrasound in pathology testis tumors

Se presentan 19 pacientes con testiculos tumorales estudiados con ecografía (transductor de 5 MHz) y su correspondiente confirmación quirúrgica. La ecografía demostró una alta certeza diagnóstica: 96,8% para determinar la localización de una lesión escrotal (intratesticular, extratesticular o mixta). Frente a las lesiones neoplásicas, el método demostró alta sensibilidad: 100%, baja especificidad: 64%, y 85% de certeza diagnóstica. Se analizan en detalle los signos ultrasonográficos asociados a patología tumoral, así como el origen de los 5 falsos-positivos que disminuyen la especificidad ecográfica (AU)

Tratamiento del carcinoma renal avanzado / Treatment of renal carcinoma

Se comunican los resultados obtenidos en el tratamiento de 62 pacientes con carcinoma renal metastásico con el empleo de nefrectomia adyuvante y medroxiprogesterona (14 por ciento de sobrevida a los dos años), quimioterapia con vinblastina (18,7 por ciento de sobrevida a los dos años) y en protocolo reciente, nefrectomia adyuvante con inmunoterapia activa especifica (20 por ciento de sobrevida al finalizar el primer año). Se destaca la buena evolución obtenida con la resección de las metástasis únicas. La sobrevida global de pacientes con métastasis fue de 17,7 por ciento al finalizar el segundo año de tratamiento

Tratamiento del carcinoma renal avanzado / Treatment of renal carcinoma

Se comunican los resultados obtenidos en el tratamiento de 62 pacientes con carcinoma renal metastásico con el empleo de nefrectomia adyuvante y medroxiprogesterona (14 por ciento de sobrevida a los dos años), quimioterapia con vinblastina (18,7 por ciento de sobrevida a los dos años) y en protocolo reciente, nefrectomia adyuvante con inmunoterapia activa especifica (20 por ciento de sobrevida al finalizar el primer año). Se destaca la buena evolución obtenida con la resección de las metástasis únicas. La sobrevida global de pacientes con métastasis fue de 17,7 por ciento al finalizar el segundo año de tratamiento (AU)