Theories and Molecular Basis of Vascular Aging: A Review of the Literature from VascAgeNet Group on Pathophysiological Mechanisms of Vascular Aging.

Vascular aging, characterized by structural and functional alterations of the vascular wall, is a hallmark of aging and is tightly related to the development of cardiovascular mortality and age-associated vascular pathologies. Over the last years, extensive and ongoing research has highlighted several sophisticated molecular mechanisms that are involved in the pathophysiology of vascular aging. A more thorough understanding of these mechanisms could help to provide a new insight into the complex biology of this non-reversible vascular process and direct future interventions to improve longevity. In this review, we discuss the role of the most important molecular pathways involved in vascular ageing including oxidative stress, vascular inflammation, extracellular matrix metalloproteinases activity, epigenetic regulation, telomere shortening, senescence and autophagy.

Interaction between curcumin and human serum albumin in the presence of excipients and the effect of binding on curcumin photostability.

Curcumin (Cur) is known to bind to human serum albumin (HSA) which may lead to a reduced phototoxic effect of the compound in the presence of serum or saliva. The influence of excipients on the Cur-HSA binding was studied by HSA florescence quenching and Cur absorption and emission spectroscopy in the presence and absence of the selected excipients. Photostabilty of Cur in the presence of HSA was evaluated, as well as the effect of excipients on HSA bound Cur photodegradation. Cyclodextrins (CDs) (2-hydroxypropyl-ß-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin) and polymers (polyethylene glycol 400, PEG 400 and Pluronic F-127, PF-127) were selected for the study. CDs and PF-127 seem to decrease Cur binding to HSA, probably through competitive binding. Cur was still bound to HSA in polyethylene glycol (PEG) solutions at the highest investigated concentration (5% w/v). However, high PEG concentration appears to have effect on the protein conformation, as shown by the fluorescence quenching study. Low Cur photostability in the presence of HSA could be improved by the addition of hydroxylpropyl-γ-cyclodextrin (HPγCD) to the samples, whereas PEG and PF-127 showed no effect.

Poloxamer-based curcumin solid dispersions for ex tempore preparation of supersaturated solutions intended for antimicrobial photodynamic therapy.

Phototoxic effect of curcumin supersaturated solutions toward pathogenic bacteria has already been demonstrated. However, to be useful in the clinical practice, a supersaturated solution needs to be physically and chemically stabile over the relevant time period. Poloxamer-based solid dispersions (SD) intended for ex tempore preparation of a supersaturated solution were designed to simultaneously facilitate dissolution and inhibit precipitation of curcumin in vitro. Due to the transformation of the crystalline compound to an amorphous form, as shown by X-ray powder diffraction, the desired concentration of curcumin could easily be achieved upon hydration of SDs. The efficiency of selected poloxamers (Pluronic® F-127, F-68 and P-123) as the precipitation inhibitors (PIs) and influence of an additional PI (polyethylene glycol 400, hydroxypropyl methylcellulose, and hyaluronic acid) on the physical stability of the solutions were examined by UV-Vis spectrophotometry. HPLC-PDA was employed to evaluate hydrolytic and photolytic stability of curcumin in the SD solutions. At sub-micellar concentrations, Pluronics® F-127 and P-123, but not F-68, delayed curcumin precipitation in aqueous media and protected the compound from hydrolytic degradation up to 24 h. Complete inactivation of Enterococcus faecalis was achieved after exposure to solutions of selected SDs at curcumin concentration ≥1 µM and the light dose of 9.4 J/cm2.

Brugada syndrome: A general cardiologist's perspective.

Brugada syndrome (BrS) is one of the commonest inherited primary arrhythmia syndromes typically presenting with arrhythmic syncope or sudden cardiac death (SCD) due to polymorphic ventricular tachycardia and ventricular fibrillation precipitated by vagotonia or fever in apparently healthy adults, less frequently in children. The prevalence of the syndrome (0.01%-0.3%) varies among regions and ethnicities, being the highest in Southeast Asia. BrS is diagnosed by the "coved type" ST-segment elevation≥2mm followed by a negative T-wave in ≥1 of the right precordial leads V1-V2. The typical electrocardiogram in BrS is often concealed by fluctuations between normal, non-diagnostic and diagnostic ST-segment pattern in the same patient, thus hindering the diagnosis. Presently, the majority of BrS patients is incidentally diagnosed, and may remain asymptomatic for their lifetime. However, BrS is responsible for 4-12% of all SCDs and for ~20% of SCDs in patients with structurally normal hearts. Arrhythmic risk is the highest in SCD survivors and in patients with spontaneous BrS electrocardiogram and arrhythmic syncope, but risk stratification for SCD in asymptomatic subjects has not yet been fully defined. Recent achievements have expanded our understanding of the genetics and electrophysiological mechanisms underlying BrS, while radiofrequency catheter ablation may be an effective new approach to treat ventricular tachyarrhythmias in BrS patients with arrhythmic storms. The present review summarizes our contemporary understanding and recent advances in the inheritance, pathophysiology, clinical assessment and treatment of BrS patients.