A method for trimming surfaces generated as solutions to Partial Differential Equations (PDEs) is presented. The work we present here utilises the 2D parameter space on which the trim curves are defined whose projection on the parametrically represented PDE surface is then trimmed out. To do this we define the trim curves to be a set of boundary conditions which enable us to solve a low order e...

This paper presents a method to extend PDE surfaces to high dimensional spaces. We review a common existing analytic solution, and show how it can be used straightforwardly to increase the dimension of the space the surface is embedded within. We then further develop a numerical scheme suitable for increasing the number of variables that parametrise the surface, and investigate some of the prop...

In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently u...

Objective(s): Recently, we showed that some new synthetic compounds structurally related to cilostamide (4-(1,2-dihydro-2-oxoquinolin-6-hydroxy)- N-cyclohexyl-N-methylbutanamide), a selective phosphodiesterase 3 (PDE3) inhibitor, produce inotropic effect comparable to that of IBMX (3-isobutyl-1-methylxanthine), a non-selective PDE inhibitor, but with differential chronotropic effect. In this in...

Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that th...

Results During a follow-up period of 47.2 21.8 months (range 4 to 82 months), 49 patients experienced major adverse cardiac events (MACE). The difference in ED prevalence between patients with and those without MACE was significant (61.2% vs. 36.4%; p 0.001). Cox regression analysis showed that ED predicted MACE (hazard ratio [HR] 2.1; 95% confidence interval [CI] 1.6 to 2.6; p 0.001). Among pa...

Many men with erectile dysfunction (ED) also have associated underlying cardiovascular and metabolic conditions, for which they are likely to be taking medication. Therefore, cardiovascular safety and potential drug interactions are two of the major concerns when using PDE-5 inhibitors in these patients. The PDE-5 inhibitor, vardenafil, is characterized by a rapid onset of action, increased dur...

C hronic inflammatory processes are related to conditions as distinct as atherosclerosis, amyotrophic lateral sclerosis, asthma, systemic lupus, Alzheimer’s disease, and Parkinson’s disease. The continuous use of antiinflammatory agents is required to treat these conditions. However, the longterm use of these drugs creates an additional challenge: the high frequency of severe side effects. For ...

Phosphodiesterases (PDEs) are enzymes that break down the phosphodiesteric bond of the cyclic nucleotides, cAMP and cGMP, second messengers that regulate many biological processes. PDEs participate in the regulation of signal transduction by means of a fine regulation of cyclic nucleotides so that the response to cell stimuli is both specific and activates the correct third messengers. Several ...