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Introduction The use of current available treatment for male erectile dysfunction (ED) has some limitations that are related to efficacy and adverse effects. Nanotechnology has been used as a new tool in medicine to improve these limitations and new medications potentially to alleviate and cure ED. Aim To review the currently literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and to identify gaps for future research. Methods A comprehensive literature review was conducted via Google Scholar, Science Direct, and PubMed on English publications using different keywords such as “erectile dysfunction”, “emerging treatments”, “nanotechnology”, and “herbal medicine”. The retrieved papers were organized into groups according to the sections covered in this review paper. Main Outcomes Measures We reviewed novel ED treatments such as nanotechnological phosphodiesterase inhibitors, papaverine hydrochloride, sialorphin, adipose tissue-derived stem cells, sonic hedgehog, and herbal medicine. Results Numerous preclinical studies have addressed novel phosphodiesterase 5 inhibitors nanoparticle, and their recent delivery systems. Nitric oxide, sialorphin, sonic hedgehog, and herbal medicine loaded nanoparticles and nano adipose tissue-derived stem cells as a potential new treatment for ED. In addition, papaverine-containing nanoparticles have been reported. A limited number of randomized clinical studies have determined the mechanism of these treatments. Conclusion A literature review on the application of nanotechnology in ED therapy was successfully conducted. New nano medications are promising to treat ED. However, further studies are warranted to further assess their efficacy and safety.

Phosphodiesterase 3A (PDE3A) selectively cleaves the phosphodiester bond of cAMP and is inhibited by cGMP, making it an important regulator of cAMP-cGMP signaling crosstalk in the pulmonary vasculature. In addition, the nitric oxide-cGMP axis is known to play an important role in maintaining endothelial barrier function. However, the potential role of protein kinase G-Iα (PKG-Iα) in this protective process is unresolved and was the focus of our study. We describe here a novel mechanism regulating PDE3A activity, which involves a PKG-Iα-dependent inhibitory phosphorylation of PDE3A at serine 654. We also show that this phosphorylation is critical for maintaining intracellular cAMP levels in the pulmonary endothelium and endothelial barrier integrity. In an animal model of acute lung injury (ALI) induced by challenging mice with lipopolysaccharide (LPS), an increase in PDE3 activity and a decrease in cAMP levels in lung tissue was associated with reduced PKG activity upon PKG-Iα nitration at tyrosine 247. The peroxynitrite scavenger manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin prevented this increase in PDE3 activity in LPS-exposed lungs. In addition, site-directed mutagenesis of PDE3A to replace serine 654 with alanine yielded a mutant protein that was insensitive to PKG-dependent regulation. Taken together, our data demonstrate a novel functional link between nitrosative stress induced by LPS during ALI and the downregulation of barrier-protective intracellular cAMP levels. Our data also provide new evidence that PKG-Iα is critical for endothelial barrier maintenance and that preservation of its catalytic activity may be efficacious in ALI therapy.

Objective To study the effect of sildenafil citrate on spontaneous passage of distal ureteric stones (DUS). Patients and methods This was a randomised double-blinded placebo-controlled study of 100 patients with DUS. Inclusion criteria were: male, age 18–65 years, normal renal function, and a single radiopaque unilateral DUS of 5–10 mm. Patients were randomly allocated into two equal groups, one that received placebo and the other that received 50 mg sildenafil citrate once daily. Both investigators and patients were masked to the type of treatment. Patients self-administered the medication until spontaneous passage of the DUS. In patients where there was uncontrolled pain, fever, an increase in serum creatinine of >1.8 mg/dL, progressive hydronephrosis or no further progress after 4 weeks, a decision was taken for further treatment. Results In all, 47 and 49 patients were available for analysis in both the placebo and sildenafil citrate groups; respectively. Both groups were comparable for age and stone characteristics. Spontaneous expulsion occurred in 19 of 47 patients (40.4%) in the placebo group and in 33 of 49 (67.3%) in the sildenafil citrate group (P = 0.014). The mean time to stone expulsion was significantly shorter in the sildenafil citrate group (P