The "Statinth" wonder of the world: a panacea for all illnesses or a bubble about to burst

After the introduction of statins in the market as effective lipid lowering agents, they were shown to have effects other than lipid lowering. These actions were collectively referred to as 'pleiotropic actions of statins.' Pleiotropism of statins formed the basis for evaluating statins for several indications other than lipid lowering. Evidence both in favour and against is available for several of these indications. The current review attempts to critically summarise the available data for each of these indications

Interplay of Ryanodine Receptor Distribution and Calcium Dynamics

Spontaneously generated calcium (Ca(2+)) waves can trigger arrhythmias in ventricular and atrial myocytes. Yet, Ca(2+) waves also serve the physiological function of mediating global Ca(2+) increase and muscle contraction in atrial myocytes. We examine the factors that influence Ca(2+) wave initiation by mathematical modeling and large-scale computational (supercomputer) simulations. An important finding is the existence of a strong coupling between the ryanodine receptor distribution and Ca(2+) dynamics. Even modest changes in the ryanodine receptor spacing profoundly affect the probability of Ca(2+) wave initiation. As a consequence of this finding, we suggest that there is information flow from the contractile system to the Ca(2+) control system and this dynamical interplay could contribute to the increased incidence of arrhythmias during heart failure

Bradykinin receptors as a therapeutic target

Biologically-active kinins, including bradykinin (BK) and Lys(0)-BK (kallidin), are short-lived peptide mediators predominantly generated by the enzymatic action of kallikreins on kininogen precursors. A diverse spectrum of physiological and pathological actions attributed to local kinin production is a consequence of the activation of G-protein-coupled receptors (GPCRs). Currently, two major subtypes of kinin receptor, designated B(1) and B(2), are recognised, although there is much evidence for pharmacological heterogeneity, particularly within the B(2) receptors. Considering these facts and the widespread distribution of kinin receptors in many human tissues, it is no surprise that the therapeutic potential of kinins and kinin receptor antagonists remains the focus of numerous investigations. Studies in animals and animal tissues, instrumental in elucidating the biological roles of kinins, are well-documented in numerous excellent reviews. Unfortunately, and despite the enormous potential illustrated by animal studies, attempts to develop kinin analogues as therapeutic agents to combat human disease have largely proven disappointing. Consequently, this review selectively focuses upon studies that are directly relevant to the targeting of human BK receptors as a therapeutic intervention. In addition to providing a succinct review of well-documented pathological conditions to which kinin receptors contribute, the authors have also included more recent data that illustrate new avenues for the therapeutic application of kinin analogues