Publications

Human immunodeficiency virus (HIV) continues to be a major contributor to morbidity and mortality worldwide, particularly in developing nations where high cost and logistical issues severely limit the use of current HIV therapeutics. This, combined HIV's high propensity to develop resistance, means that new antiviral agents against novel targets are still urgently required. We previously identified novel anti-HIV agents directed against the nuclear import of the HIV integrase (IN) protein, which plays critical roles in the HIV lifecycle inside the cell nucleus, as well as in transporting the HIV preintegration complex (PIC) into the nucleus. Here we investigate the structure activity relationship of a series of these compounds for the first time, including a newly identified anti-IN compound, budesonide, showing that the extent of binding to the IN core domain correlates directly with the ability of the compound to inhibit IN nuclear transport in a permeabilised cell system. Importantly, compounds that inhibited the nuclear transport of IN were found to significantly decrease HIV viral replication, even in a dividing cell system. Significantly, budesonide or its analogue flunisolide, were able to effect a significant reduction in the presence of specific nuclear forms of the HIV DNA (2-LTR circles), suggesting that the inhibitors work though blocking IN, and potentially PIC, nuclear import. The work presented here represents a platform for further development of these specific inhibitors of HIV replication with therapeutic and prophylactic potential.

PURPOSE OF REVIEW

This article will review the current techniques in cardiac magnetic resonance imaging (CMR) for diagnosing and assessing primary valvular heart disease.

RECENT FINDINGS

The recent advancements in CMR have led to an increased role of this modality for qualifying and quantifying various native valve diseases. Phase-contrast velocity encoded imaging is a well-established technique that can be used to quantify aortic and pulmonic flow. This technique, combined with the improved ability for CMR to obtain accurate left and right ventricular volumetrics, has allowed for increased accuracy and reproducibility in assessing valvular dysfunction. Advancements in CMR technology also allows for improved spatial and temporal resolution imaging of various valves and their regurgitant or stenotic jets. Therefore, CMR can be a powerful tool in evaluation of native valvular heart disease. The role of CMR in assessing valvular heart disease is growing and being recognized in recent guidelines. CMR has the ability to assess valve morphology along with qualifying and quantifying valvular disease. In addition, the ability to obtain accurate volumetric measurements may improve more precise management strategies and may lead to improvements in mortality and morbidity.