Cosmeceuticals: practical applications

Cosmeceuticals are topically applied products that are more than merely cosmetic, yet are not true drugs that have undergone rigorous placebo controlled studies for safety and efficacy. There are many review articles that outline the theoretical biologic and clinical actions of these cosmeceuticals and their various ingredients. This article reviews how to incorporate various cosmeceuticals into the treatment regime of patients, depending on the diagnosis and therapies chosen. The practical application of when, why, and on whom to use different products will enable dermatologists to improve the methodology of product selection and, ultimately, improve patient's clinical results.     

IP3 receptor orchestrates maladaptive vascular responses in heart failure

Patients with heart failure (HF) have augmented vascular tone, which increases cardiac workload, impairing ventricular output and promoting further myocardial dysfunction. The molecular mechanisms underlying the maladaptive vascular responses observed in HF are not fully understood. Vascular smooth muscle cells (VSMCs) control vasoconstriction via a Ca²⁺-dependent process, in which the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) on the sarcoplasmic reticulum (SR) plays a major role. To dissect the mechanistic contribution of intracellular Ca²⁺ release to the increased vascular tone observed in HF, we analyzed the remodeling of IP3R1 in aortic tissues from patients with HF and from controls. VSMC IP3R1 channels from patients with HF and HF mice were hyperphosphorylated by both serine and tyrosine kinases. VSMCs isolated from IP3R1^VSMC–/– mice exhibited blunted Ca²⁺ responses to angiotensin II (ATII) and norepinephrine compared with control VSMCs. IP3R1^VSMC–/– mice displayed significantly reduced responses to ATII, both in vivo and ex vivo. HF IP3R^1VSMC–/– mice developed significantly less afterload compared with HF IP3R1^fl/fl mice and exhibited significantly attenuated progression toward decompensated HF and reduced interstitial fibrosis. Ca²⁺-dependent phosphorylation of the MLC by MLCK activated VSMC contraction. MLC phosphorylation was markedly increased in VSMCs from patients with HF and HF mice but reduced in VSMCs from HF IP3R1^VSMC–/– mice and HF WT mice treated with ML-7. Taken together, our data indicate that VSMC IP3R1 is a major effector of increased vascular tone, which contributes to increased cardiac afterload and decompensation in HF.     

Prothrombotic State in Atrial Fibrillation Patients With One Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex)

Background

It is unclear whether a prothrombotic state occurs in atrial fibrillation (AF) with low stroke risk.