https://uroweb.org/wp-content/uploads/14-Male-Sexual-Dysfunction_LR1.pdf

Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation.

Vascular endothelial growth factors (VEGFs) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in the adult. It is therefore important to understand the mechanism of action of this family of five mammalian ligands, which act through three receptor tyrosine kinases (RTKs). In addition, coreceptors like neuropilins (NRPs) and integrins associate with the ligand/receptor signaling complex and modulate the output. Therapeutics to block several of the VEGF signaling components have been developed with the aim to halt blood vessel formation, angiogenesis, in diseases that involve tissue growth and inflammation, such as cancer. In this review, we outline the current information on VEGF signal transduction in relation to blood and lymphatic vessel biology.

/pdf/signal-transduction-by-vascular-endothelial-growth-factor-2km99omtgf.pdf

Signal Transduction by Vascular Endothelial Growth Factor Receptors

The main challenge for all electrical, mechanical and optical sensors is to detect low molecular weight (less than 400 Da) chemical and biological analytes under extremely dilute conditions. Surface plasmon resonance sensors are the most commonly used optical sensors due to their unique ability for real-time monitoring the molecular binding events. However, their sensitivities are insufficient to detect trace amounts of small molecular weight molecules such as cancer biomarkers, hormones, antibiotics, insecticides, and explosive materials which are respectively important for early-stage disease diagnosis, food quality control, environmental monitoring, and homeland security protection. With the rapid development of nanotechnology in the past few years, nanomaterials-enhanced surface plasmon resonance sensors have been developed and used as effective tools to sense hard-to-detect molecules within the concentration range between pmol and amol. In this review article, we reviewed and discussed the latest trend and challenges in engineering and applications of nanomaterials-enhanced surface plasmon resonance sensors (e.g., metallic nanoparticles, magnetic nanoparticles, carbon-based nanomaterials, latex nanoparticles and liposome nanoparticles) for detecting “hard-to-identify” biological and chemical analytes. Such information will be viable in terms of providing a useful platform for designing future ultrasensitive plasmonic nanosensors.

Nanomaterials enhanced surface plasmon resonance for biological and chemical sensing applications

Oxytocin: the Great Facilitator of Life

Vascular endothelial growth factors and angiogenesis in eye disease.

By real-time RT-PCR and Western blot analysis, we found that phosphodiesterase type 5 (PDE5) mRNA and protein abundance was several fold higher in human male than in female reproductive tracts. The highest mRNA level (>1 × 107 molecules/μg total RNA) was detected in human corpora cavernosa (CC), where PDE5 protein was immunolocalized in both muscular and endothelial compartment. The possible role of androgens in regulating PDE5 expression was studied using a previously established rabbit model of hypogonadotropic hypogonadism. In this model, hypogonadism reduced, and testosterone (T) supplementation restored, CC PDE5 gene and protein expression. In addition, T supplementation completely rescued and even enhanced cyclic GMP conversion to metabolites, without changing IC50 for sildenafil (IC50 = 2.16 ± 0.62 nm). In control CC strips, sildenafil dose-dependently increased relaxation induced by electrical field stimulation, with EC50 = 3.42 ± 1.7 nm. Hypogonadism reduced, and T increased, sildenafil effect on...

/pdf/androgens-regulate-phosphodiesterase-type-5-expression-and-4pybucki1y.pdf

Androgens Regulate Phosphodiesterase Type 5 Expression and Functional Activity in Corpora Cavernosa

Benign prostate hyperplasia is the most common disease in the aging male, often comorbid with erectile dysfunction. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) decrease lower urinary tract symptoms in patients with erectile dysfunction and BPH. We studied PDE5 expression and activity in the human bladder and PDE5i effects both in vitro (human and rat) and in vivo (rat). PDE5 is highly expressed in rat and human bladder and immunolocalized in vascular endothelium and muscle fibers. Sildenafil, tadalafil, and vardenafil blocked 70% of the total cGMP-catabolizing activity; vardenafil was the most potent (IC50 = 0.3 nm). In human bladder cells and in rat strips, a PDE-resistant cGMP analog, SP-8-Br-PET-cGMPS, induced, respectively, a consistent antiproliferative and relaxant effect. In contrast, the nitric oxide donor sodium nitroprusside (SNP) was almost ineffective. However, blocking PDE5 with vardenafil increased SNP antiproliferative and relaxant activity up to the l...

/pdf/characterization-and-functional-role-of-androgen-dependent-3kuh7isg5w.pdf

Characterization and Functional Role of Androgen-Dependent PDE5 Activity in the Bladder

Characterization and functional role of an androgen-dependent PDE5 activity in bladder

Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum.

Metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) are often associated. One of their common denominators is hypogonadism. However, testosterone supplementation is limited by concerns for potential prostatic side effects. The objective was to determine whether MetS-associated prostate alterations are prevented by testosterone supplementation. We used a previously described animal model of MetS, obtained by feeding male rabbits a high-fat diet (HFD) for 12 weeks. Subsets of HFD rabbits were treated with testosterone or with the farnesoid X receptor agonist INT-747. Rabbits fed a standard diet were used as controls. HFD-animals develop hypogonadism and all the MetS features: hyperglycemia, glucose intolerance, dyslipidemia, hypertension, and visceral obesity. In addition, HFD-animals show a prostate inflammation. Immunohistochemical analysis demonstrated that HFD-induced prostate fibrosis, hypoxia, and inflammation. The mRNA expression of several proinflammatory (IL8, IL6, IL1b, and TNFa), T lymphocyte (CD4, CD8, Tbet, Gata3, and ROR gt), macrophage (TLR2, TLR4, and STAMP2), neutrophil (lactoferrin), inflammation (COX2 and RAGE), and fibrosis/myofibroblast activation (TGFb, SM22a, aSMA, RhoA, and ROCK1/ROCK2) markers was significantly increased in HFD prostate. Testosterone, as well as INT-747, treatment prevented some MetS features, although only testosterone normalized all the HFD-induced prostate alterations. Interestingly, the ratio between testosterone and estradiol plasma level retains a significant, negative, association with all the fibrosis and the majority of inflammatory markers analyzed. These data highlight that testosterone protects rabbit prostate from MetS-induced prostatic hypoxia, fibrosis, and inflammation, which can play a role toward the development/progression of BPH/LUTS.

/pdf/testosterone-protects-from-metabolic-syndrome-associated-4zhl0lv85d.pdf

Sandra Filippi

Papers

Androgens Regulate Phosphodiesterase Type 5 Expression and Functional Activity in Corpora Cavernosa

Characterization and Functional Role of Androgen-Dependent PDE5 Activity in the Bladder

Characterization and functional role of an androgen-dependent PDE5 activity in bladder

Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum.

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit.