Alteration in Claudin-4 Contributes to Airway Inflammation and Responsiveness in Asthma

PURPOSE: Claudin-4 has been reported to function as a paracellular sodium barrier and is one of the 3 major claudins expressed in lung alveolar epithelial cells. However, the possible role of claudin-4 in bronchial asthma has not yet been fully studied. In this study, we aimed to elucidate the role of claudin-4 in the pathogenesis of bronchial asthma. METHODS: We determined claudin-4 levels in blood from asthmatic patients. Moreover, using mice sensitized and challenged with OVA, as well as sensitized and challenged with saline, we investigated whether claudin-4 is involved in the pathogenesis of bronchial asthma. Der p1 induced the inflammatory cytokines in NHBE cells. RESULTS: We found that claudin-4 in blood from asthmatic patients was increased compared with that from healthy control subjects. Plasma claudin-4 levels were significantly higher in exacerbated patients than in control patients with bronchial asthma. The plasma claudin-4 level was correlated with eosinophils, total IgE, FEV1% pred, and FEV1/FVC. Moreover, lung tissues from the OVA-OVA mice showed significant increases in transcripts and proteins of claudin-4 as well as in TJ breaks and the densities of claudin-4 staining. When claudin-4 was knocked down by transfecting its siRNA, inflammatory cytokine expressions, which were induced by Der p1 treatment, were significantly increased. CONCLUSIONS: These findings thus raise the possibility that regulation of lung epithelial barrier proteins may constitute a therapeutic approach for asthma.

Methacholine bronchial provocation test in patients with asthma: serial measurements and clinical significance

BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.

Impact of the Endothelial Tight Junction Protein Claudin-5 on Clinical Profiles of Patients With COPD

PURPOSE: The tight junction protein claudin-5 (CLDN5) is critical to the control of endothelial cellular polarity and pericellular permeability. The role of CLDN5 in chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the association between CLDN5 levels and clinical variables in patients with COPD. METHODS: In total, 30 patients with COPD and 30 healthy controls were enrolled in the study. The plasma CLDN5 level was checked in patients with stable or exacerbated COPD and in healthy controls. RESULTS: The mean plasma CLDN5 level of patients with COPD was 0.63 ± 0.05 ng/mL and that of healthy controls was 6.9 ± 0.78 ng/mL (P = 0.001). The mean plasma CLDN5 level was 0.71 ± 0.05 ng/mL in exacerbated COPD patients and 0.63 ± 0.04 ng/mL in patients with stable COPD (P < 0.05). The plasma CLDN5 level among COPD subjects was correlated with the smoking amount (r = −0.530, P = 0.001). The plasma CLDN5 level in stable COPD patients was correlated with forced expiratory volume in one second (FEV1, %pred.) (r = −0.481, P = 0.037). CONCLUSIONS: The plasma CLDN5 level was not correlated with age. CLDN5 may be involved in the pathogenesis of COPD. Further studies having a larger sample size will be needed to clarify CLDN5 in COPD.

Effect of TiO₂ Nanoparticles on Inflammasome-Mediated Airway Inflammation and Responsiveness

PURPOSE: Nanoparticles (NPs) may cause cell and tissue damage, leading to local and systemic inflammatory responses and adverse effects on health due to the inhalation of particulate matter. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (pro-IL-1β) into its mature form and may induce acute and chronic immune responses to NPs. However, little is known about the response of the inflammasome to NP exposure via the airways in asthma. The aim of this study was to identify the impact of titanium dioxide (TiO2) NPs on inflammasome in a mouse model of allergic asthma. METHODS: Mice were treated with ovalbumin (OVA) or TiO₂ NPs. IL-1β, IL-18, NAIP, CIITA, HET-E, TP-2 (NACHT), leucine-rich repeat (LRR), pyrin domain-containing protein 3 (NLRP3), and caspase-1 were assessed by Western blotting. Caspase-1 was assessed by immunohistochemistry (IHC). Levels of reactive oxygen species (ROS)—as markers of oxidative damage—and the mediators 8-isoprostane and carbonyl were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Airway hyperresponsiveness (AHR) and inflammation were increased in OVA-sensitized/challenged mice, and these responses were exacerbated by exposure to TiO₂ NPs. NP treatment increased IL-1β and IL-18 expression in OVA-sensitized/challenged mice. NPs augmented the expression of NLRP3 and caspase-1, leading to production of active caspase-1 in the lung. Caspase-1 expression was increased and exacerbated by TiO₂ NP exposure in OVA-sensitized/challenged mice. ROS levels tended to be increased in OVA-sensitized/challenged and OVA-sensitized/challenged-plus-TiO₂ NP-exposed mice. CONCLUSIONS: Our data demonstrated that inflammasome activation occured in asthmatic lungs following NP exposure, suggesting that targeting the inflammasome may assist in controling NP-induced airway inflammation and hyperresponsiveness.

Factors Influencing Metabolic Syndrome among Mental Health Facility Patients with Schizophrenia / 정신간호학회지

PURPOSE: This study was done to identify prevalence of, and factors influencing metabolic syndrome among long-term care facility patients with schizophrenia. METHODS: A cross-sectional survey was conducted using a 20-item questionnaire. Clinical data for blood triglyceride, HDL-cholesterol, and fasting blood sugar were collected from medical records. Body weight, body fat, body mass index, blood pressure, height, and abdominal circumference were measured. Data for 198 participants were analyzed using t-test, x2 test and logistic regression. RESULTS: Prevalence of metabolic syndrome was 56.1%. The number of persons who overate was significantly higher in the metabolic syndrome group than in the normal group (p<.001). Factors influencing metabolic syndrome were hyperphagia (p<.001), abdominal circumference (p<.001), systolic blood pressure (p=.040), blood triglyceride (p<.001), fasting blood sugar (p=.015), and HDL-cholesterol (p<.001). CONCLUSION: The results indicate that nurses working with patients who have chronic schizophrenic should make an effort to help patients achieve control of overeating behavior and reduce abdominal circumference to prevent metabolic syndrome.

The Correlation between 2nd to 4th Digit Length Ratio and Characteristics of Temperament and Character in University Students

OBJECTIVES: The 2nd to 4th digit length(2D:4D) ratio reflects the amount of exposure and sensitivity to the prenatal sex hormone and it is considered to be the most convenient and useful way to understand the influence of sex hormone in the determination of human behavioral traits. This study was carried out to find the correlation between the 2D:4D ratio and characteristics of temperament and character in Korean university students. We assumed that 2D:4D ratio would show a strong correlation with temperament which is defined to be an inclination of an automatical emotional response to a stimulus. METHODS: Participants were 104 university students who completed 2 self-report measures:Temperament and Character Inventory(TCI), Temperament Test. We examined the 2D:4D ratio of each subject by measuring the lengths of the 2nd and 4th fingers using a photocopy measurement. We performed statistical analyses using correlation test and t-test to examine the relationship between 2D:4D ratio and psychological characteristics. RESULTS: We found out the typical sex difference in 2D:4D ratio. Women had significantly higher 2D:4D ratio than men. TCI-Character factor(TCI-C) didn't show any significant correlation with the 2D:4D ratio. TCI-Tempterament factor(TCI-T) and the item of Temperament Test showed a significant correlation with the 2D:4D ratio. In correlation analysis of the total group including all women and men, the 2D:4D ratio showed a significant positive correlation in a subscale(shyness with stranger) of harm avoidance scales in TCI-T. In correlation analysis of women's group, the 2D:4D ratio showed a significant positive correlation in two subscales( fear of uncertainty) and[shyness to stranger] of harm avoidance scales in TCI-T. In correlation analysis of men's group, the 2D:4D ratio showed a significant negative correlation with a sanguine temperament item of the Temperament Test. CONCLUSION: The results suggest that the amount of exposure to sex hormone in the prenatal period seems to have an impact on the determination of temperament and characteristics.

A Pilot Study of Brief Eye Movement Desensitization and Reprocessing(EMDR) for Treatment of Acute Phase Schizophrenia

OBJECTIVES: Eye movement desensitization and reprocessing(EMDR) is a novel, time-limited psychotherapy originally developed for treatment of psychological trauma. The effectiveness of this therapy has been validated only for posttraumatic stress disorder; however, EMDR is often applied to other psychiatric illnesses, including other anxiety disorders and depression. This pilot study tested the efficacy of EMDR added to the routine treatment for individuals with acute stage schizophrenia. METHODS: This study was conducted in the acute psychiatric care unit of a university-affiliated training hospital. Inpatients diagnosed with schizophrenia were randomly assigned to either three sessions of EMDR, three sessions of progressive muscle relaxation(PMR) therapy, or only treatment as usual(TAU). All the participants received concurrent typical treatments(TAU), including psychotropic medication, individual supportive psychotherapy and group activities in the psychiatric ward. The Positive and Negative Syndrome Scale(PANSS), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were administered by a clinical psychologist who was blinded to the patients' group assignment. RESULTS: Forty-five patients enrolled and forty patients(89%) completed the post-treatment evaluation. There were no between-group differences in the withdrawal rates of patients during the treatment or at the three-month follow-up session. All three groups improved significantly across each of the symptomatic domains including schizophrenia, anxiety, and depressive symptoms. However, a repeated measures ANOVA revealed no significant differences among the groups over time. Effect size for change in total PANSS scores was also similar across treatment conditions, but effect size for negative symptoms was large for EMDR(0.60 for EMDR, 0.39 for PMR and 0.21 for TAU only). CONCLUSION: These findings supported the use of EMDR in treating the acute stage of schizophrenia but the results failed to confirm the effectiveness of the treatment over the two control conditions in three sessions. Further studies with longer courses of treatment, more focused target dimensions of treatment, and a sample of outpatients are necessary.

Construction and Validation of Hospital-Based Cancer Registry Using Various Health Records to Detect Patients with Newly Diagnosed Cancer: Experience at Asan Medical Center / 예방의학회지

OBJECTIVES: An accurate estimation of cancer patients is the basis of epidemiological studies and health services. However in Korea, cancer patients visiting out-patient clinics are usually ruled out of such studies and so these studies are suspected of underestimating the cancer patient population. The purpose of this study is to construct a more complete, hospital-based cancer patient registry using multiple sources of medical information. METHODS: We constructed a cancer patient detection algorithm using records from various sources that were obtained from both the in-patients and out-patients seen at Asan Medical Center (AMC) for any reason. The medical data from the potentially incident cancer patients was reviewed four months after first being detected by the algorithm to determine whether these patients actually did or did not have cancer. RESULTS: Besides the traditional practice of reviewing the charts of in-patients upon their discharge, five more sources of information were added for this algorithm, i.e., pathology reports, the national severe disease registry, the reason for treatment, prescriptions of chemotherapeutic agents and radiation therapy reports. The constructed algorithm was observed to have a PPV of 87.04%. Compared to the results of traditional practice, 36.8% of registry failures were avoided using the AMC algorithm. CONCLUSIONS: To minimize loss in the cancer registry, various data sources should be utilized, and the AMC algorithm can be a successful model for this. Further research will be required in order to apply novel and innovative technology to the electronic medical records system in order to generate new signals from data that has not been previously used.

Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression

Unmethylated CpG oligodeoxynucleotides (CpG ODNs) activate immune cells to produce immune mediators. This study demonstrates that in murine macrophage RAW 264.7 cells, CpG ODN-mediated matrix metalloproteinase-9 (MMP-9) expression is regulated at transcriptional level and requires de novo protein synthesis. Inhibition of ERK and p38 MAPK, but not JNK, results in significant decrease of CpG ODN-induced MMP-9 expression. We found that endosomal maturation inhibitors, chloroquine and bafilomycin A, block CpG ODN-induced ERK and p38 MAPK activation and the subsequent MMP-9 expression. We also observed that CpG ODN induces NF-kappa B activation and NF-kappa B is a downstream target of p38 MAPK. Taken together, our data demonstrate that CpG ODN triggers MMP-9 expression via TLR-9 dependent ERK and p38 MAPK activation followed by NF-kappa B activation.