Differences in preventing new-onset cardiovascular events with statin therapy in seniors aged 75 years and over: A cohort study in the South Korean National Health Insurance Database.

The aim of this cohort study was to compare the effectiveness of statin regimens for primary prevention among seniors aged ≥ 75 years. Seniors aged 75-100 years for whom statin therapies for primary prevention were newly initiated between 1 January 2009 and 31 December 2011, and who continued the same statin regimen during the first year after the index date were identified using the claims data from the South Korean National Health Insurance Database. A propensity score matching and multivariable Cox proportional hazards model were developed to evaluate adjusted ischaemic cardiovascular-cerebrovascular event (CCE) risk and all-cause mortality risk for all patients, as well as for subgroups. A total of 5629 older patients aged 75-100 years were included in the study population. Compared to moderate-intensity statin therapy, low-intensity statin therapy was significantly associated with increased risk of ischaemic CCEs, while high-intensity statin therapy was associated with reduced risk of ischaemic CCEs; however, compared to moderate-intensity statin therapy, both low-intensity and high-intensity statin therapies were associated with increased risk of all-cause mortality. For the 4689 older patients who regularly received moderate-intensity statin therapy including 10 mg atorvastatin, 20 mg atorvastatin, 10 mg rosuvastatin or 20 mg simvastatin for primary prevention, multivariable regression adjusting for potential covariates revealed no significant difference in ischaemic CCEs or all-cause mortality between the moderate-intensity statin users and 10 mg atorvastatin users both before and after propensity scoring matching. No significant heterogeneity was detected in the patient subgroups. The results of this study based on real-world data can supply evidence-based reasons for choice of statin regimen for the primary prevention of CCEs in older people aged ≥ 75 years.

Polyphenols differentially inhibit degranulation of distinct subsets of vesicles in mast cells by specific interaction with granule-type-dependent SNARE complexes.

Anti-allergic effects of dietary polyphenols were extensively studied in numerous allergic disease models, but the molecular mechanisms of anti-allergic effects by polyphenols remain poorly understood. In the present study, we show that the release of granular cargo molecules, contained in distinct subsets of granules of mast cells, is specifically mediated by two sets of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, and that various polyphenols differentially inhibit the formation of those SNARE complexes. Expression analysis of RBL-2H3 cells for 11 SNARE genes and a lipid mixing assay of 24 possible combinations of reconstituted SNAREs indicated that the only two active SNARE complexes involved in mast cell degranulation are Syn (syntaxin) 4/SNAP (23 kDa synaptosome-associated protein)-23/VAMP (vesicle-associated membrane protein) 2 and Syn4/SNAP-23/VAMP8. Various polyphenols selectively or commonly interfered with ternary complex formation of these two SNARE complexes, thereby stopping membrane fusion between granules and plasma membrane. This led to the differential effect of polyphenols on degranulation of three distinct subsets of granules. These results suggest the possibility that formation of a variety of SNARE complexes in numerous cell types is controlled by polyphenols which, in turn, might regulate corresponding membrane trafficking.

Protective effects of Haematococcus astaxanthin on oxidative stress in healthy smokers.

Free radicals induced by cigarette smoking have been strongly linked to increased oxidative stress in vivo, contributing to the pathobiology of various diseases. This study was performed to investigate the effects of Haematococcus astaxanthin (ASX), which has been known to be a potent antioxidant, on oxidative stress in smokers. Thirty-nine heavy smokers (≥20 cigarettes/day) and 39 non-smokers were enrolled in this study. Smokers were randomly divided into three dosage groups to receive ASX at doses of 5, 20, or 40 mg (n=13, each) once daily for 3 weeks. Oxidative stress biomarkers such as malondialdehyde, isoprostane, superoxide dismutase, and total antioxidant capacity, and ASX levels in plasma were measured at baseline and after 1, 2, and 3 weeks of treatment. Compared with baseline, the plasma malondialdehyde and isoprostane levels decreased, whereas superoxide dismutase level and total antioxidant capacity increased in all ASX intervention groups over the 3-week period. In particular, isoprostane levels showed a significant dose-dependent decrease after ASX intake. The results suggest that ASX supplementation might prevent oxidative damage in smokers by suppressing lipid peroxidation and stimulating the activity of the antioxidant system in smokers.

Inhibition of SNARE-driven neuroexocytosis by plant extracts.

Neuronal soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins mediate membrane fusion between synaptic vesicle and presynaptic membrane, resulting in neurotransmitter release. SNARE proteins are specific substrates of botulinum neurotoxins (BoNT) which are now widely used for therapeutic and cosmetic purposes. While BoNT blocks neuroexocytosis by cleaving SNAREs, inhibiting SNARE assembly process might exert the same effect on neurotransmission. In the present study, some extracts of 100 plants reduced neurotransmitter release by inhibiting SNARE complex formation in neuronal cells. The extracts effectively paralyzed muscle of rat phrenic nerve-hemidiaphragm preparation. Our results raise the possibility that SNARE folding inhibitors from natural resources might replace some special BoNT application fields.