Background: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. Methods: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. Results: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. Conclusion A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Purpose: The aim of this study is to demonstrate the association between recurrent atrial fibrillation (AF) and left ventricular (LV) adverse remodeling after catheter ablation and to evaluate the change of myocardial extracellular volume fraction (ECV) by catheter ablation outcomes. Materials and Methods: We retrospectively recruited 60 patients (44 men and 16 women) with a median age of 57 years (range, 32–78 years) who underwent cardiac MRI before and at 6–12 months after catheter ablation of AF. Cardiac MRI quantified myocardial ECV (%) in the left ventricle. Depending on myocardial ECV after catheter ablation, patients were divided into two groups: 1) LV adverse remodeling with ECV ≥ 28%; and 2) no adverse LV remodeling with ECV < 28%. Multivariable analysis was performed to assess the association between recurrent AF and LV remodeling. Results: Of 60 patients, 21 (35%) were in the LV adverse remodeling group (mean ECV ± standard deviation [SD]: 29.8% ± 1.4%) and 39 (65%) were in the no adverse LV remodeling group (mean ECV ± SD: 24.7% ± 1.5%). The incidence of recurrent AF was significantly greater in the LV adverse remodeling group than in the no adverse LV remodeling group (81% vs. 13%, p < 0.001). In patients with recurrent AF, mean myocardial ECV significantly increased from 27.7% ± 2.3% to 29.2% ± 2.3% (p = 0.004) after catheter ablation. In a multivariable analysis after adjusting sex, age, and myocardial ECV before catheter ablation, recurrent AF was independently associated with LV adverse remodeling after catheter ablation (odds ratio: 28.9, 95% confidence interval: 6.8–121.7, p < 0.001). Conclusion When monitoring with cardiac MRI, sustained AF was significantly associated with LV adverse remodeling through an increase in myocardial ECV after catheter ablation of AF.

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines including tumor necrosis factor-α and interleukin-1β in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of NF-κB p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.
Antioxidants ; Cytokines ; Dinoprostone ; Genes, Regulator ; Inflammation* ; Larva ; Macrophages* ; Necrosis ; Neutrophils ; Nitric Oxide ; Oxidative Stress* ; Reactive Oxygen Species ; Spermidine* ; Zebrafish*

BACKGROUND/OBJECTIVES: In this study, the apoptogenic activity and mechanisms of cell death induced by hexane extract of aged black garlic (HEABG) were investigated in human leukemic U937 cells. MATERIALS/METHODS: Cytotoxicity was evaluated by MTT (3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide) assay. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. RESULTS: Exposure to HEABG was found to result in a concentration- and time-dependent growth inhibition by induction of apoptosis, which was associated with an up-regulation of death receptor 4 and Fas legend, and an increase in the ratio of Bax/Bcl-2 protein expression. Apoptosis-inducing concentrations of HEABG induced the activation of caspase-9, an initiator caspase of the mitochodrial mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. HEABG also induced apoptosis via a death receptor mediated extrinsic pathway by caspase-8 activation, resulting in the truncation of Bid, and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. However, pre-treatment of U937 cells with the caspase-3 inhibitor, z-DEVD-fmk, significantly blocked the HEABG-induced apoptosis of these cells, and increased the survival rate of HEABG-treated cells, confirming that HEABG-induced apoptosis is mediated through activation of caspase cascade. CONCLUSIONS: Based on the overall results, we suggest that HEABG reduces leukemic cell growth by inducing caspase-dependent apoptosis through both intrinsic and extrinsic pathways, implying its potential therapeutic value in the treatment of leukemia.
Apoptosis* ; Blotting, Western ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cell Death ; Electrophoresis, Agar Gel ; Flow Cytometry ; Garlic* ; Humans* ; Leukemia ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Survival Rate ; U937 Cells* ; Up-Regulation

BACKGROUND AND OBJECTIVES: The thioredoxin (TRx) system is a ubiquitous thiol oxidoreductase pathway that regulates cellular reduction/oxidation status. Although endothelial cell (EC) hypoxic damage is one of the important pathophysiologic mechanisms of ischemic heart disease, its relationship to the temporal expression pattern of the TRx system has not yet been elucidated well. The work presented here was performed to define the expression pattern of the TRx system and its correlation with cellular apoptosis in EC lines in hypoxic stress. These results should provide basic clues for applying aspects of the TRx system as a therapeutic molecule in cardiovascular diseases. SUBJECTS AND METHODS: Hypoxia was induced with 1% O2, generated in a BBL GasPak Pouch (Becton Dickinson, Franklin Lakes, NJ, USA) in human endothelial progenitor cells (hEPC) and human umbilical vein endothelial cells (HUVEC). Apoptosis of these cells was confirmed by Annexin-V: Phycoerythrin flow cytometry. Expression patterns of TRx; TRx reductase; TRx interacting protein; and survival signals, such as Bcl-2 and Bax, in ECs under hypoxia were checked. RESULTS: Apoptosis was evident after hypoxia in the two cell types. Higher TRx expression was observed at 12 hours after hypoxia in hEPCs and 12, 36, 72 hours of hypoxia in HUVECs. The expression patterns of the TRx system components showed correlation with EC apoptosis and cell survival markers. CONCLUSION: Hypoxia induced significant apoptosis and its related active changes of the TRx system were evident in human EC lines. If the cellular impact of TRx expression pattern in various cardiovascular tissues under hypoxia or oxidative stress was studied meticulously, the TRx system could be applied as a new therapeutic target in cardiovascular diseases, such as ischemic heart disease or atherosclerosis.
Anoxia ; Apoptosis ; Atherosclerosis ; Cardiovascular Diseases ; Cell Hypoxia ; Cell Survival ; Endothelial Cells ; Flow Cytometry ; Human Umbilical Vein Endothelial Cells ; Humans ; Lakes ; Myocardial Ischemia ; Oxidative Stress ; Phycoerythrin ; Stem Cells ; Thioredoxins

Bites and Stings ; Bone Screws ; Humans ; Lip ; Mandible ; Mastication ; Orthodontics ; Osteogenesis, Distraction ; Osteotomy ; Tooth ; Tooth Mobility ; Walking

BACKGROUND AND OBJECTIVES: Chronobiological rhythms have been shown to influence the occurrence of a variety of cardiovascular disorders, including acute myocardial infarction (AMI). The present study investigated whether the onset of acute aortic syndrome (AAS) has unique chronobiological rhythms in Korean populations. SUBJECTS AND METHODS: The clinical data of 371 consecutive AAS patients, admitted between 1993 and 2003, were retrospectively analyzed; 310 AMI patients, who underwent primary percutaneous angioplasty in the hyperacute phase between 1998 and 2001, were also selected. RESULTS: In the AAS group, the final diagnoses were aortic dissection (AD) and aortic intramural hematoma (AIH) in 212 and 159 patients, respectively Similar to AMI, AAS showed a significantly higher occurrence from 6 AM to noon compared with other time periods (p=0.0013). AAS showed a second peak occurrence from 6 PM to midnight, which was not observed in the AMI group. A subgroup analysis revealed that younger patients (age < 60 years) and those with a past medical history of hypertension had the highest occurrence from 6 PM to midnight, which was quite different compared to the AAS patients. No significant variation was found for the day of the week in either group. Although no significant seasonal variation was observed in the frequency of AMI, the frequency of AAS was significantly higher during winter (p<0.001). The circadian and seasonal variations in the frequency of AIH were similar to those of AD. CONCLUSION: AAS shows unique circadian and seasonal variations in Korean populations. Our findings may have implications for the prevention of AAS by tailoring treatment strategies to ensure maximal benefits during the vulnerable periods.
Angioplasty ; Circadian Rhythm ; Diagnosis ; Hematoma ; Humans ; Hypertension ; Myocardial Infarction* ; Retrospective Studies ; Seasons

BACKGROUND AND OBJECTIVES: Platelet-derived growth factor (PDGF) seems to be one of the most powerful factors associated with the proliferative process that occurs after percutaneous transluminal coronary angioplasty (PTCA), and leads to restenosis. Trapidil (Triazolopyrimidine), a potent inhibitor of PDGF, was shown to decrease restenosis after experimental balloon angioplasty. The aim of this study was to assess the effects of trapidil, on intimal hyperplasia, following coronary artery stenting, using volumetric intravascular ultrasound (IVUS) analysis. SUBJECTS AND METHODS: The patients were divided in 2 groups; Group I (n=14, age=53+/-8, male=11) received trapidil (600 mg) for 6 months, aspirin (200 mg) indefinitely and ticlopidine (250 mg) for 4 weeks, Group 2 (n=15, age=55+/-2, male=9) received aspirin (200mg) indefinitely and ticlopidine (500 mg) for 4 weeks, starting at least 3 days before the angioplasty. A serial IVUS study was performed post-stenting, with a 6 month follow up period. Both the stent (SA) and lumen areas (LA) were measured, and the stent (SV), lumen (LV) and intimal hyperplasia volumes (IHV) were calculated using Simpson's rule. RESULTS: The reference (RD), pre minimal luminal (MLD) and post minimal luminal diameters, as measured by quantitative coronary angiographic analysis (QCA), were not different between the two groups. Using serial IVUS measurements, SV and LV were not different between the two groups. Also, the IHV was not different between the two groups (51.9+/-26.1 and 61.3+/-25.3 mm3, respectively, p=NS). CONCLUSION: Trapidil failed to reduce intimal hyperplasia following coronary stenting compared with the controls.
Angioplasty ; Angioplasty, Balloon ; Angioplasty, Balloon, Coronary ; Aspirin ; Coronary Vessels ; Follow-Up Studies ; Humans ; Hyperplasia* ; Phenobarbital ; Platelet-Derived Growth Factor* ; Stents* ; Ticlopidine ; Trapidil ; Ultrasonics ; Ultrasonography*

PURPOSE: To describe the angiographic findings of patients with recurrent hemoptysis after bronchial artery embolization (BAE) according to the point at which relapse occurred. MATERIALS AND METHODS: From 125 patients who underwent BAE due to hemoptysis between 1996 and 2000, we selected 18 of 23 who underwent additional BAE due to recurrent bleeding after initial BAE . Depending on the point at which relapse occurred, they were divided into two groups (I and II, according to whether additional BAE was performed within two weeks of initial BAE or more than two weeks after this). We retrospectively compared the two groups in terms of angiographic findings, number of embolized arteries, and character of feeding arteries at initial and additional BAE. RESULTS: Nine patients in group I (additional BAE: n=10) and nine in group II (additional BAE: n=13) were admitted for recurrent hemoptysis within two weeks of initial BAE and more than two weeks after this, respectively. In group I(n=29) and II(n=31), angiography demonstrated two direct and 27 indirect, and two direct and 29 indirect signs of hemorrhage, respectively. No statistically significant differences were observed (x2=0.005, p=0.945). Among the embolized feeder ressels in group I (n=30) there were 20 bronchial artery and 10 non bronchial systemic collaterals, while for group II(n=35), the corresponding totals were 21 and 14. Again, no statistically significant differences were encountered(x2=0.308; p=0.579). In group I, feeders were newly developed in one case(10%), previously embolized in five(50%), and missed in four(40%), while in group two the corresponding figures were none, twelve(92.3%), and one(7.7%). No significant differences were noted, though the incidence of previously embolized feeders in Group II was very high (x2=5.383, p=0.068). CONCLUSION: Among patients in whom hemoptysis after BAE recurred at different times, the angiographic findings and number of embolized arteries were not significantly different, but differences in the nature of the feeder were noted. Patients in whom hemoptysis recurred more than two weeks after BAE showed more recanalization of previously embolized feeders than those in whom there was recurrence within two weeks.
Angiography ; Arteries ; Bronchial Arteries ; Hemoptysis* ; Hemorrhage* ; Humans ; Incidence ; Recurrence ; Retrospective Studies