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The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy.

Since IgG4-related pancreatitis was first reported in 2001, IgG4-related disease has been identified in other organs such as salivary gland, gallbladder, thyroid, retroperitoneum and kidney; but lung invasion is rare. A 63-year-old man presented with hemoptysis at the pulmonary clinic and chest computed tomography revealed about 4.1 cm irregular shaped mass with spiculated margin at the left upper lobe. Despite no elevation of serum IgG4 level, he was finally diagnosed as IgG4-related lung disease by transthoracic needle biopsy. After treatment with oral glucocorticoids, hemoptysis disappeared and the size of lung mass was decreased.

Inter-cell interference hinders multi-cellular optical wireless communication to support various applications. We proposed and experimentally demonstrated a multicarrier-based cell partitioning scheme, combined with frequency reuse, which could be effective in optical communications although it is inefficient in RF wireless communications. For multicarrier-based cell partitioning, Orthogonal frequency division multiplexing-based multiple access (OFDMA) was employed to accommodate multi-cellular optical wireless communications without a large guard band between adjacent cells and without additional RF components. Moreover, we employed filter bank-based multicarrier (FBMC) to mitigate inter-cell interference generated in OFDMA-based cell partitioning due to asynchronous signals originated from RF path difference. By using FBMC-based cell partitioning, inter-cell interference could be effectively mitigated as well as capacity and spectral efficiency were improved about 1.5 times compared to those of OFDMA. Because no cyclic prefix (CP) is required in FBMC, the improvement factor could be increased if there is a large RF path difference between lighting cells. Moreover, it could be a stronger solution when many neighboring cells exist causing large interference. The proposed multicarrier-based cell partitioning combined with FBMC will effectively support visible light communication (VLC)-based localization-based services (LBS) and indoor positioning system by transparently providing trilateration-based positioning method.

Background: Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis., Methods: We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases., Results: A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied., Conclusions: This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.

Ginseng has been used for thousands of years in Asian countries as a traditional medicinal herb and has gained great popularity in the past decade. Ginsenosides are the major pharmacological components in ginseng. We here show that Cladosporium cladosporioide is able to convert the major ginsenoside Rb1 into four known metabolites (ginsenosides Rd, F2, CK and PPD) and two new metabolites [12β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside (3-oxo-CK) and dammar-24-en-12β,20(S)-diol-3-one (3-oxo-PPD)]. CK, PPD and 3-oxo-PPD were shown to have a potent antiproliferative activity against A549 lung cancer cells. We found that Rb1 → Rd → F2 → CK → PPD or 3-oxo-CK → 3-oxo-PPD represents the ginsenoside metabolic pathway.

Background: The purpose of this study was to evaluate the risk factors for mechanical ventilation in the patients with scrub typhus admitted to intensive care unit (ICU) at a university hospital., Methods: We retrospectively selected and analyzed clinical data from the medical records of 70 patients (32 men, 38 women) admitted to the ICU with scrub typhus between 2004 and 2014. The patients had a mean±standard deviation age of 71.2±11.1 years and were evaluated in two groups: those who had been treated with mechanical ventilation (the MV group, n=19) and those who had not (the non-MV group, n=51). Mean ages of the MV group and the non-MV group were 71.2±8.3 years and 71.2±11.1 years, respectively., Results: Significant differences between the two groups were observed with respect to acute respiratory failure (p=0.008), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p=0.015), Sequential Organ Failure Assessment (SOFA) score (p=0.013), death (p=0.014), and ICU duration (p<0.01). Multivariate analysis indicated that the following factors were significantly associated with mechanical ventilation: acute respiratory failure (p=0.011), SOFA score (p=0.005), APACHE II score (p=0.011), platelet count (p=0.009), and lactate dehydrogenase (LDH) (p=0.011)., Conclusion: Thus, five factors-acute respiratory failure, SOFA score, APACHE II score, platelet count, and LDH-can be the meaningful indicators for mechanical ventilation for the patients with scrub typhus admitted to ICU.

Objectives: An outbreak of joint and cutaneous infections among patients who had been injected at a single clinic in South Korea was investigated., Methods: In this retrospective case-control study, 61 cases were diagnosed based on symptoms and signs of septic arthritis or cutaneous infection that developed after injections at the clinic between April and September 2012; 64 controls were investigated by administering questionnaires on risk factors and analyzing the clinic medical records. An environmental investigation was performed, and clinical specimens of the cases were analyzed by pulsed-field gel electrophoresis., Results: All cases were injected with triamcinolone. A greater number of triamcinolone injections (adjusted odds ratio 4.3, 95% confidence interval 1.5-12.1 for six or more visits, compared with one or two visits) was associated with the development of an infection. In the clinic, only the triamcinolone injection was prepared by mixing with lidocaine and normal saline, and an alcohol swab was prepared using boiled tap water by members of the clinic staff. Although injected medications and environmental cultures were not found to be responsible, a single strain of Mycobacterium massiliense was isolated from the affected sites of 16 cases., Conclusions: Repeated injection of triamcinolone contaminated with NTM from the clinic environment may have caused this post-injection outbreak., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In orthogonal frequency division multiple access based passive optical network (OFDMA-PON) uplink, synchronization between optical network units (ONUs) is very important to maintain orthogonality. The synchronization among uplink signals is considered as one of the main challenges in OFDMA-PON due to optical path difference. In this paper, the performance degradation according to timing offset between ONUs is experimentally analyzed. And we propose and demonstrate timing offset effect reduction in asynchronous multiple access by using CP extension and filter bank based multicarrier (FBMC) system in intensity modulation/direct detection (IM/DD) based OFDMA-PON uplink transmission.

Diabetes is a metabolic disorder, and it is considered as a major risk factor for Alzheimer's disease (AD). In the present study, we evaluated whether treadmill exercise ameliorates progression of AD in relation with glycogen synthase kinase-3β (GSK-3β) activity using streptozotocin (STZ)-induced diabetic rats. For this study, step-down avoidance task, immunohistochemistry for glycogen synthase kinase-3β (GSK-3β) and tau, and western blot for phosphor-phosphoinositide 3 kinase (p-PI3K)/PI3K and phosphor-Akt (p-Akt)/Akt were performed. Diabetes mellitus was induced by intraperitoneal injection of STZ. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, five times a week, during 12 weeks. The present results showed that short-term and long-term latencies in the step-down avoidance task were decreased by induction of diabetes, and treadmill exercise inhibited these latencies in the diabetic rats. Induction of diabetes suppressed the ratio of p-PI3K to PI3K and the ratio of p-Akt to Akt, and treadmill exercise increased these ratios in the diabetic rats. The numbers of GSK-3β-positive and tau-positive cells in the hippocampal dentate gyrus was higher in the diabetes-induction group than that in the control group, and treadmill exercise inhibited these numbers in the diabetic rats. In the present study, treadmill exercise suppressed hyperphosphorylation of tau in the hippocampus by decreased GSK-3β activity through PI3K/Akt pathway activation in the diabetic rats. Based on the present results, treadmill exercise may helpful to prevent diabetes-associated AD occurrence.

We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of 70/µL. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months.

[Purpose] The present study examined the influence of treadmill exercise added to a low back pain rehabilitation program on low back extensor strength, pain, and dysfunction in chronic low back pain patients. [Subjects and Methods] Twenty men aged 22-36 years with chronic low back pain were randomly divided into experimental and control groups of 10 patients each. Both groups underwent a low back pain rehabilitation program lasting 30 min each, thrice/week for 8 weeks. The experimental group was prescribed an additional 30 min of treadmill exercise without a slope at a speed of 3.0-3.5 km/h, at which patients could walk comfortably. Low back extensor strength was tested using the Medx lumbar extension machine, pain level was tested, using the visual analog scale, and dysfunction was tested, using the Oswestry Low Back Pain Disability Questionnaire. [Results] Changes in low back extensor strength by angle showed significant interaction effects between measurement time and group at 12°, 24°, and 36°. The results of the visual analog scale and Oswestry Questionnaire showed a decreasing trend after the experiment in both groups. However, there was no interaction effect of the additional treadmill exercise in the experimental group. [Conclusion] The combination of a low back pain rehabilitation program and treadmill exercise has a synergistic effect, to some extent, on the improvement of low back extensor strength and should be considered for treatment and rehabilitation of low back pain patients.

Purpose: This study was conducted to develop and test a hypothetical model to predict health outcomes in young people with type 2 diabetes., Methods: Data were collected from 190 adults aged 23-45 with type 2 diabetes mellitus who visited the endocrinology outpatient department of the two university hospitals in South Korea from November 2, 2012 to March 7, 2013. Data collection used the structured questionnaires and patient medical records. The descriptive and correlation statistics were analyzed using PASW 18.0 and structural equation modeling procedure was performed using the AMOS 18.0 program., Results: The fit of the hypothetical model was appropriate with the ratio of the chi-square statistic to degrees of freedom at 17.00, goodness-of-fit index at .975, adjusted goodness-of-fit index at .930, root mean square error of approximation at .061, normed fit index at .926, Turker-Lewis index at .929, comparative fit index at .966. Behavioral skills were a critical factor that directly affects self-management behaviors. Through behavioral skills, motivation had a statistically significant indirect effect on self-management behavior. Self-management behavior had a statistically significant direct effect on health outcome. Through self-management behavior, behavioral skills had a statistically significant indirect effect on health outcome. These variables explained 17.9% of the total variance for the health outcome in young people with type 2 diabetes., Conclusions: The results suggest that self-management behavior could be improved through nursing interventions promoting personal motivation (positive attitude), social motivation (social support), and behavioral skills (self efficacy), which can result in better health outcomes for young people with type 2 diabetes., (Copyright © 2015. Published by Elsevier B.V.)

Background: Low-dose aspirin is recommended to reduce the risk of cardiovascular disease. However, the questions with regard to primary prevention have been raised among patients with diabetes. We evaluated low-dose aspirin use for preventing ischemic stroke in patients with diabetes using a national health insurance database., Methods: Using data from the Korean Health Insurance Review and Assessment Service database from January 1, 2005, through December 31, 2009, a population-based retrospective cohort study was conducted with incident patients with diabetes aged 40 to 99 years old with the initial use of low-dose aspirin during the index period from January 1, 2006 to December 31, 2007. We matched each low-dose aspirin user to one non-user using a propensity score. The Cox proportional hazards model was used to compare the risk of hospitalization for ischemic stroke in users and nonusers of low-dose aspirin until December 31, 2009., Results: Out of 261,065 incident patients with diabetes, 15,849 (6.2%) were low-dose aspirin users. Compared to non-users, the adjusted hazard ratio (95% confidence interval) of low-dose aspirin users for hospitalization due to ischemic stroke was 1.73 (95% CI; 1.41-2.12). In a sensitivity analysis of study subjects with more than 1 year follow-up periods, slightly higher adjusted hazard ratio (1.97, 95% CI; 1.51-2.62) was observed. In the subgroup analyses, there were no significant changes in the risk of hospitalization for ischemic stroke irrespective of gender, age, or comorbidity., Conclusions: In this study of patients with diabetes, the use of low-dose aspirin showed an increased risk of hospitalization for ischemic stroke. These results suggest that low-dose aspirin use for the primary prevention of ischemic stroke should be reconsidered in patients with diabetes.

Objectives: Depression and diabetes are closely biologically and behaviorally intertwined. We examined the impact of comorbid diabetes mellitus on the incidence of serious psychiatric outcomes among patients with depression., Methods: We used claims data from the Korean Health Insurance Review & Assessment Service database of patients who were diagnosed with depression within one year of an index prescription for antidepressants between January 2007 and June 2008. We investigated the association between the comorbidity of diabetes mellitus and serious psychiatric outcomes of depression, such as psychiatric hospitalization, psychiatric emergency room visits, and suicide attempts., Results: Among 200,936 patients with depression, 74,160 (36.9%) had diabetes mellitus, including 57,418 (28.6%) with complications. The incidence of serious psychiatric outcomes was 3.3% in patients with depression without diabetes and 6.7% in patients with depression and diabetes mellitus. Patients with depression and diabetes mellitus complications showed higher rates of serious outcomes than that did those without diabetes mellitus complications (odds ratio, 1.19; 95% confidence interval, 1.11-1.13). Similarly, depressed patients with micro and macrovascular diabetic complications were more likely to experience serious outcomes than those without diabetes mellitus complications (odds ratio, 2.2; 95% confidence interval, 2.07-2.34)., Conclusions: Our results showed that comorbid diabetes mellitus can increase the risk of serious outcomes of depression, such as suicide and hospitalization, and thus may alter the antidepressants prescription patterns and healthcare service use among patients with depressive disorders., (© The Author(s) 2015.)

Trachelospermi caulis is used widely as an herbal medicine in oriental countries to attenuate fever and pain. We wished to reveal the novel function of this herb and its active component on barrier function in intestinal epithelial cells. Monolayers of intestinal epithelial cells (Caco-2) were used to evaluate the transepithelial electrical resistance (TEER) and quantity of permeated ovalbumin (OVA) as indices of barrier function. T. caulis increased TEER values on cell monolayers and decreased OVA permeation across cell monolayers. To ascertain the active component of T. caulis, the extract was isolated to five fractions, and the effect of each of these fractions on intestinal barrier function examined. Chloroform and ethyl acetate fractions showed increased TEER values and decreased OVA flux. Chloroform and ethyl acetate fractions contained mainly trachelogenin and its glycoside, tracheloside. Trachelogenin increased TEER values and decreased OVA flux by enhancing the tight-junction protein occludin (but not tracheloside) in Caco-2 monolayers. These findings demonstrated that trachelogenin, an active component of T. caulis, might help to attenuate food allergy or inflammatory bowel disease through inhibition of allergen permeation or enhancement of the intestinal barrier.

Objective: The purpose of this study was to investigate the aortic isthmus (AoI) flow difference between larger fetus and smaller fetus of twin; and to evaluate the predictive value of early diagnosis of hemodynamic change in twin growth., Methods: This prospective study on 49 pairs of twin fetuses was performed to obtain AoI blood flow data. Cases with structural or chromosomal abnormalities and co-twin death were excluded. The interval from examination to delivery was within 4 weeks and 3 cases over 4 weeks interval were re-examined. Assessment of fetal AoI Doppler parameters were peak systolic velocity (PSV), end-diastolic velocity, times-averaged maximum velocities, pulsatility index (PI), and resistance index (RI). According to the direction of the diastolic flow in the AoI, antegrade and retrograde flow were made and was used to analyze the perinatal outcomes of each fetus. The predictive value of AoI Doppler parameters in predicting fetal growth was obtained by using ANOVA and logistic regression analysis of quantitative variables in each fetus of twins., Results: There were significant differences in the gestational weeks at delivery, birth weight and the incidence of growth discordance over 20% or more between monochorionic twin and dichorionic twin. The AoI PI and RI were significantly higher in smaller fetus than in larger regardless of chorionicity. Retrograde flow was noted in 8 of 98 cases (8.2%) and the only one case was of the larger fetus and the others were smaller fetuses of twin. Significant correlations were found between the AoI PI and birthweight (P=0.018) and between the PSV and growth discordance (P=0.032). In monochorionic twin, linear correlation was shown between the AoI PI and birthweight (P=0.004) and between AoI PI and growth discordance (P=0.031). Also, the meaningful correlation between the PSV and birthweight (P=0.036) was found by using logistic regression analyses., Conclusion: On the basis of our observation, AoI PI has revealed their hemodynamic status and this result may improve the understanding of growth patterns in twins.

Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function.

Ginsenosides are the major pharmacological components in ginseng. We isolated lactic acid bacteria from Kimchi to identify microbial modifications of ginsenosides. Phylogenetic analysis of 16S rRNA gene sequences indicated that the strain DCY65-1 belongs to the genus Lactobacillus and is most closely related to Lactobacillus brevis. On the basis of TLC and HPLC analysis, we found two metabolic pathways: F1 → 6α,12β-dihydroxydammar-3-one-20(S)-O-β-D-glucopyranoside and C-K → 12β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside. These results suggest that strain DCY65-1 is capable of potent ketonic decarboxylation, ketonizing the hydroxyl group at C-3. The F1 metabolite had a more potent inhibitory effect on mushroom tyrosinase than did the substrate. Therefore, the F1 and C-K derivatives may be more pharmacologically active compounds, which should be further characterized.

Purpose: Pharmacovigilance plays a vital role in ensuring that patients receive appropriate medical products that are safe and effective. This paper aims to describe the history of pharmacovigilance in Korea and introduce the establishment and goal of the KIDS., Methods: In Korea, the adverse drug reactions (ADR) reporting system was launched in 1988 by the Korea Ministry of Food and Drug Safety (MFDS) and spontaneous ADR reports have been collected from health care professionals and the general public. Although the ADR reporting system has begun, the reporting rate was very low in the first 10 years, and safety actions were done passively in response to the US Food and Drug Administration (FDA) or European Medicines Agency (EMA)'s safety alert and communications., Results: Therefore, the Korea Institute of Drug Safety and Risk Management (KIDS) was established in April 2012 as a new initiative for pharmacovigilance., Conclusions: The KIDS will continue to contribute to the improvement of Korean pharmacovigilance by collecting, managing, and analyzing consumer-centered drug safety information., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: The aim of this study was to establish a pancreatic tumor model of mouse using the electroporation-enhanced Sleeping Beauty (SB) transposon system., Methods: The SB transposon system was used in conjunction with electroporation to deliver oncogenes, c-Myc and HRAS, and shRNA against p53 into the mouse pancreas to induce tumors. Oncogenes (c-Myc and HRAS) and shRNA against p53 gene were directly injected into the pancreas of the mouse along with in vivo electroporation applied on the injection site. The tumors were identified grossly and confirmed using animal positron emission tomographic imaging. The tumors were then characterized using histological and immunohistochemical techniques. The expression of the targeted genes (c-Myc, HRAS, and p53) was analyzed by a real-time quantitative polymerase chain reaction., Results: Pancreatic tumors were successfully induced. The tumor phenotype was a sarcomatoid carcinoma, which was verified through immunohistochemistry. Some cysts or duct-like structures suggested to be metaplastic acinar cells were visible in the induced tumor., Conclusions: The SB transposon enhanced with electroporation can readily generate pancreatic tumors in the mice, and thus, this model serves as a valuable resource for the mouse models of pancreatic cancer.

Apoptosis occurring secondary to spinal cord injury (SCI) causes further neural damage and functional loss. In this study, a rat model was used to investigate the effect of treadmill exercise on SCI-induced apoptosis and expression of neurotrophic factors. To produce SCI, a contusion injury (10 g × 25 mm) was applied subsequent to laminectomy at the T9-T10 level. Following SCI, treadmill exercise was performed for six weeks. Hindlimb motor function was evaluated with a grid-walking test. The expression of neurotrophic factors and the level of apoptosis at the site of SCI were determined by western blotting. SCI reduced hindlimb motor function and suppressed expression of neurotrophin (NT)-3 and insulin-like growth factor (IGF)-1. Expression of phosphatidylinositol 3-kinase (PI3K), the ratio of phosphorylated Akt to Akt (pAkt/Akt) and the ratio of B-cell lymphoma 2 (Bcl-2) to Bax (Bcl-2/Bax) were decreased, and cleaved caspase-3 expression was increased by SCI. Treadmill exercise enhanced hindlimb motor function and increased expression of nerve growth factor (NGF), NT-3 and IGF-1 in the SCI rats. Treadmill exercise increased PI3K expression, the pAkt/Akt and the Bcl-2/Bax ratios, and suppressed cleaved caspase-3 expression in the injured spinal cord. This study demonstrated that treadmill exercise promotes the recovery of motor function by suppressing apoptosis in the injured spinal cord. The beneficial effect of exercise may be attributed to the increase in expression of neurotrophic factors via activation of the PI3K/Akt pathway.

Background: Chronic heart failure accounts for a great deal of the morbidity and mortality in the aging population. Evidence-based treatments include angiotensin-2 receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, and aldosterone antagonists. Underutilization of these treatments in heart failure patients were frequently reported, which could lead to increase morbidity and mortality. The aim of this study was to evaluate the utilization of evidence-based treatments and their related factors for elderly patients with chronic heart failure., Methods: This is retrospective observational study using the Korean National Health Insurance claims database. We identified prescription of evidence based treatment to elderly patients who had been hospitalized for chronic heart failure between January 1, 2005, and June 30, 2006., Results: Among the 28,922 elderly patients with chronic heart failure, beta-blockers were prescribed to 31.5%, and ACE-I or ARBs were prescribed to 54.7% of the total population. Multivariable logistic regression analyses revealed that the prescription from outpatient clinic (prevalent ratio, 4.02, 95% CI 3.31-4.72), specialty of the healthcare providers (prevalent ratio, 1.26, 95% CI, 1.12-1.54), residence in urban (prevalent ratio, 1.37, 95% CI, 1.23-1.52) and admission to tertiary hospital (prevalent ratio, 2.07, 95% CI, 1.85-2.31) were important factors associated with treatment underutilization. Patients not given evidence-based treatment were more likely to experience dementia, reside in rural areas, and have less-specialized healthcare providers and were less likely to have coexisting cardiovascular diseases or concomitant medications than patients in the evidence-based treatment group., Conclusions: Healthcare system factors, such as hospital type, healthcare provider factors, such as specialty, and patient factors, such as comorbid cardiovascular disease, systemic disease with concomitant medications, together influence the underutilization of evidence-based pharmacologic treatment for patients with heart failure.

The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.

Purpose: To compare the prescribing patterns of thiazolidinediones (TZDs) in elderly patients with type 2 diabetes with and without heart failure (HF)., Methods: The national health insurance claims database from the Health Insurance Review & Assessment Service (HIRA), Korea was used. Elderly patients with type 2 diabetes taking at least one hypoglycemic agent were studied between July 1, 2005 and June 30, 2006. Patients were grouped according to the presence of HF. The proportion of patients receiving TZDs were compared between the two groups, and stratified by their diabetes medication regimen (monotherapy and combination therapy). The difference in the patterns of TZD prescribed was studied across all health care levels including: primary, secondary, and tertiary care facilities., Results: Among 357,855 elderly patients with type 2 diabetes, 24,746 patients had HF. TZDs were prescribed to 10.4% of the patients with HF and 8.8% of the patients without HF (p < 0.01). In the combination therapy group, the proportion of patients receiving TZDs was 17.9% and 14.4% in patients with and without HF, respectively (p < 0.01). In the primary care setting, the proportion of TZD prescriptions in patients with HF was 5.6% and it was 4.6% in patients without HF (p < 0.01)., Conclusions: TZDs were frequently prescribed to patients with HF, even though the TZDs were contraindicated in patients with HF. Health care professionals should consider alternative therapies for patients with type 2 diabetes mellitus. In addition, they should carefully monitor the impact of TZD use in patients with HF., (Copyright © 2011 John Wiley & Sons, Ltd.)

Aim: To evaluate the possibility of an association between polyethylene glycol (PEG) and acute renal failure (ARF) in elderly patients using a health insurance claims database., Methods: We conducted a population-based case-crossover study using information obtained from Korean Health Insurance Review and Assessment Service (HIRA) claims from January 1, 2005 to December 31, 2005 (Seoul, Korea). The study population consisted of elderly patients who received PEG prior to experiencing their first ARF-related hospitalization from April 1, 2005 to December 31, 2005. For each patient, one case and two control periods were matched. PEG use in a 2- or 4-wk window period prior to hospitalization for ARF was compared with PEG use in two earlier 2- or 4-wk control window periods. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI, adjusting for concomitant uses of diuretics, angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, anti-cancer drugs, and contrast media., Results: Within the HIRA database which contained 1,093,262 elderly patients, 1156 hospitalized ARF cases were identified. Among these cases, PEG was prescribed to 17 (1.5%) patients before hospitalization. The adjusted ORs when applying the 2- and 4-wk window periods were 0.4 (95% CI: 0.03-5.24) and 2.1 (95% CI: 0.16-27.78), respectively., Conclusion: No increased risk of ARF was found in elderly PEG users. However, based on the limited number of study subjects, further analysis should be performed to confirm these results.

Background and Objective: Pemetrexed have been approved for the treatment of patients affected by advanced non-small cell lung cancer (NSCLC) in progression after first-line chemotherapy. We evaluated the activity and feasibility of pemetrexed in previously treated NSCLC., Methods: Patients with histologically or cytologically confirmed NSCLC were evaluated from April 2007 to March 2009. The patients had relapsed or progressed after prior chemotherapy treatment. Pemetrexed (500 mg/m²) was administered intravenously once every 3 weeks after progression to prior chemotherapy. The tumor response was evaluated according to RECIST criteria by chest CT at every 2 cycles of chemotherapy., Results: A total 61 patients were eligible for analysis. Performance status of them (100%) was over 2. The response rate and disease control rate were 14.7% and 37.7% respectively. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (P=0.045) and disease control rate (P=0.008). The median survival time and the median progression free survival (PFS) time were 6.11 months and 2.17 months, respectively. Comparing the efficacy of pemetrexed in these two settings [second-line versus (12/61) more than third (49/61)], there was no significant difference in regard to median survival (11.18 months vs 11.46 months, P=0.922,5), but PFS was more longer in third- or further-line groups than second-line group (1.39 months vs 2.25 months, P=0.015,3)., Conclusions: Pemetrexed is a feasible regimen in previously treated NSCLC with poor performance status.

In this study, we quantitatively investigated the temperature-dependent phase transition behaviors of thin films of an interesting amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly(11-[4-(4-butylphenylazo)phenoxy]undecyl methacrylate) (p(EO)-b-p(MAAZ)) and the resulting morphological structures by using synchrotron grazing incidence X-ray scattering (GIXS) and differential scanning calorimetry. The quantitative GIXS analysis showed that the diblock copolymer in the homogeneous, isotropic melt state undergoes phase-separation near 190 degrees C and then forms a body-centered cubic (BCC) structure of spherical p(EO) domains in the p(MAAZ) matrix, at which point the p(EO) domains and the p(MAAZ) matrix are both in amorphous, liquid states. The BCC structure of spherical p(EO) domains is converted to a hexagonal cylinder structure near 120 degrees C, which is induced by the transformation of the isotropic phase of the p(MAAZ) matrix to the smectic A phase, which is composed of a laterally ordered structure of p(MAAZ) blocks with fully extended side groups. The resulting hexagonal cylinder structure is very stable below 120 degrees C. This microscopic hexagonal cylinder structure is retained as the smectic A phase of the p(MAAZ) matrix undergoes further transitions to smectic C near 104 degrees C and to a smectic X phase near 76 degrees C, while the amorphous, liquid phase of the p(EO) cylinders undergoes crystallization near -15 degrees C. These complicated temperature-dependent disorder-order and order-order phase transitions in the films were found to take place reversibly during the heating run. A face-centered orthorhombic structure of p(EO) domains was also found during the heating run and is an intermediate structure in the hexagonal cylinder structure to BCC structure transformation. We use these structural analysis results to propose molecular structure models at various temperatures for thin films of the diblock polymer.

Previously, we demonstrated that pyrrolidine dithiocarbamate (PDTC) induced G1 cell cycle arrest in vascular smooth muscle cells (VSMC) through inducing p21WAF1 expression. It has recently been reported that the transcription factors involved in p21WAF1 activation by certain signaling factors may vary in different cell types. However, little is known concerning the molecular mechanisms by which PDTC induces p21WAF1 gene expression in VSMC. In this report, we demonstrate that PDTC induces the p21WAF1 expression at the mRNA level. This increase in p21WAF1 gene expression was due to p38MAPK-dependent activation of the p21WAF1 promoter by PDTC. Transcription factor Sp1 binding site was identified as the cis-element for the activation of p21WAF1 promoter by PDTC, as determined by deletion and mutation analysis. In addition, gel shift and supershift assays demonstrated that this PDTC-responsive element binds specifically to the transcription factor Sp1. Treatment with SB203580, an inhibitor of the p38MAPK, significantly down-regulated transactivation of PDTC-induced Sp1. Finally, the transient expression of VSMC with dominant negative p38MAPK plasmid suppressed PDTC-stimulated Sp1 activity. In conclusion, we report the novel finding that transcription factor Sp1 that is involved in the p38MAPK-mediated control of p21WAF1 regulation on VSMC in response to PDTC has now been identified.

Pyrrolidine dithiocarbamate (PDTC), a metal chelating compound, is known to induce cell death in vascular smooth muscle cells (VSMC). However, the molecular mechanism for PDTC-induced VSMC death is not well understood. Addition of PDTC reduced cell growth and DNA synthesis on VSMC in low density conditions. However, in serum depleted medium, PDTC did not affect the cell viability, suggesting that certain factors in serum may mediate the cytotoxic effect of PDTC. Several metal chelators prevented the cell death induced by PDTC. In a serum-deprived condition, addition of exogenous metals, copper, iron, and zinc, restored the cytotoxic effect of PDTC. These data indicate that metals such as copper, iron, and zinc in serum may mediate the cytotoxic effect of PDTC. At low VSMC density in 10% FBS, treatment of PDTC, which induced a cell-cycle block in G1-phase, induced down-regulation of cyclins and CDKs and up-regulation of the CDK inhibitor p21 expression, whereas up-regulation of p27 or p53 by PDTC was not observed. Finally, we determined PDTC-mediated signaling pathway involved in VSMC death. Among relevant pathways, PDTC induced marked activation of p38MAPK and JNK. Expression of dominant negative p38MAPK and SB203580, a p38MAPK specific inhibitor, blocked PDTC-dependent p38MAPK, growth inhibition, and p21 expression. These data demonstrate that the p38MAPK pathway participates in p21 induction, which consequently leads to decrease of cyclin D1/cdk4 and cyclin E/cdk2 complexes and PDTC-dependent VSMC growth inhibition. In conclusion, an understanding of the molecular mechanisms of PDTC in VSMC provides a theoretical basis for clinical approaches using antioxidant therapies in atherosclerosis., (Copyright 2003 Wiley-Liss, Inc.)

Many studies suggested that cyclin-dependent kinase inhibitor (CDKI) p21 acts as a universal inhibitor of cyclin/CDK catalytic activity. This protein has also been shown to be a component of active cyclin/CDK complexes. In addition, it has recently been suggested that p21 serves as an assembly factor in platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMC). However, little is known concerning the molecular mechanisms by which PDGF induces p21 gene expression in VSMC. In this report we demonstrate that PDGF induces the p21 expression at both the mRNA and protein levels. This increase in p21 gene expression was due to activation of the p21 promoter by PDGF. Through both deletion and mutation analysis of the p21 promoter, we defined a 10-bp sequence that is required for the activation of the p21 promoter by PDGF. In addition, gel shift and supershift assays demonstrated that this PDGF-responsive element binds specifically to the transcription factor Sp1. These results demonstrate that Sp1 mediates PDGF-induced p21 gene expression in VSMC. Moreover, immunoblot and immunoprecipitation analysis showed that the level of hyperphosphorylated retinoblastoma protein (Rb) is increased and the protein is physically associated with Sp1 in PDGF-treated cells, indicating that phosphorylated Rb may play a role in regulating Sp1 to activate p21 expression.