Dynamin-dependent vesicle twist at the final stage of clathrin-mediated endocytosis.

Dynamin has an important role in clathrin-mediated endocytosis by cutting the neck of nascent vesicles from the cell membrane. Here, using gold nanorods as cargos to image dynamin action during live clathrin-mediated endocytosis, we show that, near the peak of dynamin accumulation, the cargo-containing vesicles always exhibit abrupt, right-handed rotations that finish in a short time (~0.28 s). The large and quick twist, herein named the super twist, is the result of the coordinated dynamin helix action upon GTP hydrolysis. After the super twist, the rotational freedom of the vesicle increases substantially, accompanied by simultaneous or delayed translational movement, indicating that it detaches from the cell membrane. These observations suggest that dynamin-mediated scission involves a large torque generated by the coordinated actions of multiple dynamins in the helix, which is the main driving force for vesicle scission.

What Accounts for the Relationship Between Internet Use and Suicidal Ideation of Korean Older Adults? A Mediation Analysis.

OBJECTIVES: This study sought to examine the relationship between Internet use and suicidal ideation in Korean older adults and the mediating roles of social relationships and depressive symptoms. METHOD: A nationally representative sample of older adults aged 50 or older (N = 6,306), from four waves of the Korean Welfare Panel Study, was used in the analyses. All analyses were conducted using generalized estimation equations, and the mediation effects of social relationship satisfaction and depression in the relationship between Internet use and suicidal ideation were calculated using the product-of-coefficients approach. RESULTS: Internet use was linked with lower levels of suicidal ideation directly and indirectly via the protective effects of Internet use on lowering depression, which was partially mediated by the positive influence Internet use has on older adults' social relationship satisfaction. DISCUSSION: The results support previous theories about the relationship between social relationships, depression, and suicidal behavior and prior results about how the Internet might confer mental and social health benefits to older adults. This suggests that the Internet is an important social and health activity that contributes to lowering suicidal ideation in older adults.

Scanning Ion Conductance Microscopic Study for Cellular Uptake of Cationic Conjugated Polymer Nanoparticles.

Positively charged conjugated polymer nanoparticles (CPNs) are emerging biomaterials exhibiting high levels of cellular entry. High rate of cellular entry efficiency is believed that the amphiphilic CPNs interact efficiently with the negatively charged hydrophobic cellular membranes. For the first time, the cell surface morphological changes of human cervical cancer cells treated with CPNs using a scanning probe microscopy technique, scanning ion conductance microscopy (SICM) are imaged. After 1 h of CPN incubation, distinct changes are observed in cell surface morphology such as interconnected protrusions and pits with sub-micrometer sizes, which are not observed from cells treated with positively charged polyethyleneimine (PEI) under the same treatment conditions. The change on cell surface morphology is quantified by surface roughness ratio, which is increased as CPN concentration increases, while the ratio first increases and then decreases as the incubation time increases. These results suggest that cells respond actively toward CPN with both positive charges on the side chain and the hydrophobicity from rigid aromatic backbone, which leads to subsequent endocytosis. In conclusion, it is demonstrated that SICM is a suitable imaging technique to reveal the dynamic alternations on the cell surface morphology at the early stage of nanoparticles endocytosis with high resolution.

Paclitaxel- versus sirolimus-eluting stents for treatment of ST-segment elevation myocardial infarction: with analyses for diabetic and nondiabetic subpopulation.

OBJECTIVES: The aim of this study was to determine which drug-eluting stent (DES) is preferable for the treatment of ST-segment elevation myocardial infarction (STEMI) and to elucidate the impact of diabetes mellitus on the outcome of each DES. BACKGROUND: Recent studies have shown the benefit of DES in patients with STEMI. Diabetes mellitus might differentially affect outcomes of each DES. METHODS: We analyzed the large-scale, prospective, observational KAMIR (Korea Acute Myocardial Infarction Registry) study, which enrolled 4,416 STEMI patients (26% with diabetes) treated with paclitaxel-eluting stent (PES) or sirolimus-eluting stent (SES). Primary outcome was major adverse cardiac event (MACE), defined as a composite of mortality, nonfatal myocardial infarction, and target lesion revascularization (TLR). RESULTS: In the overall population, the MACE rate at 1 year was significantly higher in the PES than the SES group (11.6% vs. 8.6%, p = 0.014), which was mainly due to increased TLR (3.7% vs. 1.8%, p < 0.001). In the diabetic subgroup, however, the MACE rate was not significantly different between PES and SES (14.5% vs. 12.3%, p = 0.217), in contrast to the nondiabetic subgroup, where PES was inferior to SES as in the overall population. Matching by propensity-score did not significantly alter these results. For TLR, there was interaction between the type of stents and diabetes mellitus (unadjusted: p = 0.052; after propensity-score matching: p = 0.035). CONCLUSIONS: The PES was inferior to the SES in the overall population, with regard to the occurrence of MACE and TLR. However, subgroup analysis for diabetic subjects showed no differences in clinical outcomes between PES and SES. These results suggest that diabetes differentially affects the outcome of first-generation DES.

Intensive pharmacologic treatment in patients with acute non ST-segment elevation myocardial infarction who did not undergo percutaneous coronary intervention.

BACKGROUND: The aim of this study was to assess the impact of more aggressive pharmacological treatment on short-term clinical outcomes in patients with acute non ST-segment elevation myocardial infarction (NSTEMI) who do not undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: The 924 NSTEMI patients treated with early conservative strategy (69.2+/-12.5 years, 637 males) in 50 hospitals that were high-volume centers with facilities for primary PCI were recruited to the Korean Acute Myocardial Infarction Registry (KAMIR) from November 2005 to August 2007. For all patients, the pharmacotherapy index based on the use of drugs during hospital stay was assessed (range of points 0-10). Primary endpoint was the combined in-hospital mortality and morbidity and major adverse cardiac events during 1 month of clinical follow-up. Of the patients, data from 847 who were followed-up for 1 month after discharge were analyzed. The rate of the primary endpoint decreased with an increase of the pharmacotherapy index and this result was similar in the low- and high-risk groups. In the multivariate analysis, low pharmacotherapy index (

No differences of carotid intima-media thickness between young patients with ankylosing spondylitis and healthy controls.

OBJECTIVE: Accelerated atherosclerosis in inflammatory rheumatic diseases such as ankylosing spondylitis (AS) stands out among the leading causes of morbidity and mortality. We assessed the correlation between subclinical carotid atherosclerosis and its related clinical parameters in AS patients. METHODS: Twenty-eight patients (23 males, 5 females) with AS and 27 sex- and age-matched controls were consecutively recruited to this study. We estimated the carotid intima-media thickness (IMT) and parameters related to arterial elastic properties, including the distensibility coefficient (DC), stiffness index (beta), and incremental elastic modulus (E(inc)) using high-resolution ultrasonography. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Carotid IMT values and arterial elastic parameters in AS patients showed no statistical significance compared to those of controls (0.57+/-0.07 vs 0.55+/-0.05, p=0.387 for IMT, 28.45+/-9.23 vs 31.93+/-9.52, p=0.175 for DC, 2.32+/-0.18 vs 2.29+/-0.15, p=0.559 for stiffness index (beta), and 0.14+/-0.05 vs 0.12+/-0.03, p=0.116 for E(inc)). The serum level of IL-6 in AS patients was significantly different compared with controls (p=0.001), but not in serum levels of TNF-alpha and MCP-1 (p=0.162, p=0.087, respectively). Carotid IMT and all arterial elastic parameters calculated in this study were not found to be associated with serum levels of TNF-alpha, IL-6, and MCP-1. CONCLUSION: This cross-sectional study showed that carotid IMT and parameters related with arterial elastic properties in young AS patients without clinically evident cardiovascular risk factors were not different from those of sex- and age-matched healthy controls. Serum levels of TNF-alpha, IL-6, and MCP-1 did not reflect the degree of carotid subclinical atherosclerosis. However, these findings should be confirmed further in a larger population.

Characterization of a brown rot fungus isolated from dwarf flowering almond in Korea.

The fruits showing brown rot symptom on dwarf flowering almond were found in Gongju, Chungchungnam-Do in Korea in July 2005. Small water-soaked lesions on the fruits were initiated, and gradually developed to soft rot covered with gray conidia. Then the diseased fruits were shrunk and became grayish-black mummies. A fungus was isolated from the diseased fruit and its morphological, cultural and molecular genetic characteristics were investigated. Typical blastospores of Monilinia spp. were observed under a light microscope both from tissues of the diseased fruits and from PDA-grown cultures. The fungus grew well at 25℃ and on PDA. The ITS ribosomal DNA region (650 bp) of the fungus was amplified by PCR and analyzed. Comparative data on ITS sequence homology among Monilinia spp., ITS sequence-based phylogram and morphological characteristics showed that the fungus is Monilinia fructicola. This is the first report on Monilinia fructicola causing brown rot on fruits of dwarf flowering almond in Korea.

Do acute changes in heart rate by isoproterenol affect aortic stiffness in patients with hypertension?

BACKGROUND: Increased aortic stiffness is a independent risk factor of cardiovascular disease in patients with hypertension. Acute changes of the heart rate (HR) have been reported not to affect the aortic stiffness in pacing. However, it is unknown whether acute changes in HR caused by sympathomimetics can affect the aortic stiffness in patients with hypertension. We investigated the effect of acute changes in HR produced by isoproterenol on the aortic stiffness in 17 hypertensive patientss (mean age: 59 +/- 9 years). METHODS: All vasoactive drugs were discontinued at least 3 days before the study. The carotid-to-femoral pulse wave velocity (PWV) was measured by the foot-to-foot method. The pulse waves were recorded at the baseline and at every increase of HR by 5 to 10 bpm with a gradual increase of the dose of isoproterenol. The blood pressures and HR were measured simultaneously. For the analysis, HR, PWV, compliance (C), and compliance index (Ci) were converted as percent changes (delta) from the baseline values. Percent changes of the parameters of the aortic stiffness, i.e., deltaPWV, deltaC, and deltaCi, were grouped by every 10% increase in deltaHR. RESULTS: There was no significant difference among groups in deltaPWV, deltaC and deltaCi (p > 0.05 for each of the group). The regression analysis showed no significant correlation of deltaHR with deltaPWV and deltaC (r = 0.18, 0.13 respectively, p > 0.05 for each). deltaCi had a poor correlation with deltaHR (r = 0.22, p < 0.05). However, only 4.6% of deltaCi could be referred to deltaHR (r2 = 0.046). CONCLUSION: Aortic stiffness was not affected by acute changes in HR produced by isoproterenol which suggests that it is not necessary to consider acute changes in HR when measuring aortic PWV.

Permeation of ciclopirox across porcine hoof membrane: effect of pressure sensitive adhesives and vehicles.

The purpose of this study was to investigate the effects of various pressure sensitive adhesives (PSA) on the penetration of ciclopirox across porcine hoof membrane. In addition, the influence of various vehicles on the permeation of ciclopirox from a PSA matrix across porcine hoof membrane was evaluated using a plastic penetration chamber containing poloxamer gel at 32 degrees C. Ciclopirox in poloxamer gel was extracted, derivatized and analyzed by HPLC. Ciclopirox showed highest permeability from an acrylic adhesive with a hydroxyl functional group, and this was followed by styrene-isoprene-styrene, styrene-butadiene-styrene, silicone and polyisobutylene adhesives in order. In addition, N-methyl-2-pyrrolidone (NMP), polypropylene glycol 400 (PPG 400), dimethylsulfoxide (DMSO), Labrasol, mercaptoethanol and Transcutol showed excellent permeation enhancing effects in a styrene-isoprene-styrene adhesive. A porcine hoof membrane treated with NMP changed from the non-helical phase to the helical phase, and another treated with DMSO showed a S=O peak shift to lower wavelength.

Effects of vehicles and pressure sensitive adhesives on the penetration of isosorbide dinitrate across the hairless mouse skin.

The effects of various vehicles and adhesives on the percutaneous absorption of isosorbide dinitrate (ISDN) were evaluated. Lauroglycol FCC showed the highest flux among vehicles tested. The flux of ISDN from silicone and acrylic adhesive matrices was found to be higher than that from other types of adhesive matrices. No statistically significant relationship between the flux from acrylic PSA and the flux from a solution formulation was observed. A highly cross-linked acrylic adhesive gave higher permeation rates than the other acrylic adhesives examined. N-decylmethyl sulfoxide showed the highest enhancing effect on the flux of ISDN from acrylic adhesive. The relationship between the HLB values of vehicles and the measured flux showed a decrease of flux at HLB values greater than 12.