Min-Hye Kim

Immediate Hypersensitivity Reaction to Gadolinium-based MR Contrast Media

PURPOSE To determine the incidence and risk factors of immediate hypersensitivity reactions to gadolinium-based magnetic resonance (MR) contrast agents. MATERIALS AND METHODS Institutional review board approval and a waiver of informed consent were obtained. A retrospective study of patients who had been given gadolinium-based MR contrast media between August 2004 and July 2010 was performed by reviewing their electronic medical records. In addition to data on immediate hypersensitivity reaction, the kinds of MR contrast media and demographic data including age, sex, and comorbidity were collected. To compare the groups, the χ(2) test, Fisher exact test, χ(2) test for trend, Student t test, analysis of variance test, and multiple logistic regression test were performed. RESULTS A total of 112 immediate hypersensitivity reactions (0.079% of 141 623 total doses) were identified in 102 patients (0.121% of 84 367 total patients). Among the six evaluated MR contrast media, gadodiamide had the lowest rate (0.013%) of immediate hypersensitivity reactions, while gadobenate dimeglumine had the highest rate (0.22%). The rate for immediate hypersensitivity reactions was significantly higher in female patients (odds ratio = 1.687; 95% confidence interval: 1.143, 2.491) and in patients with allergies and asthma (odds ratio = 2.829; 95% confidence interval: 1.427, 5.610). Patients with a previous history of immediate hypersensitivity reactions had a higher rate of recurrence after reexposure to MR contrast media (30%) compared with the incidence rate in total patients (P < .0001). The incidence of immediate hypersensitivity reactions increased depending on the number of times patients were exposed to MR contrast media (P for trend = .036). The most common symptom was urticaria (91.1%), and anaphylaxis occurred in 11 cases (9.8%). The mortality rate was 0.0007% because of one fatality. CONCLUSION The incidence of immediate hypersensitivity reactions to MR contrast media was 0.079%, and the recurrence rate of hypersensitivity reactions was 30% in patients with previous reactions.

Liver-specific Inducible Nitric-oxide Synthase Expression Is Sufficient to Cause Hepatic Insulin Resistance and Mild Hyperglycemia in Mice

Inducible nitric-oxide synthase (iNOS), a major mediator of inflammation, plays an important role in obesity-induced insulin resistance. Inhibition of iNOS by gene disruption or pharmacological inhibitors reverses or ameliorates obesity-induced insulin resistance in skeletal muscle and liver in mice. It is unknown, however, whether increased expression of iNOS is sufficient to cause insulin resistance in vivo. To address this issue, we generated liver-specific iNOS transgenic (L-iNOS-Tg) mice, where expression of the transgene, iNOS, is regulated under mouse albumin promoter. L-iNOS-Tg mice exhibited mild hyperglycemia, hyperinsulinemia, insulin resistance, and impaired insulin-induced suppression of hepatic glucose output, as compared with wild type (WT) littermates. Insulin-stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) and -2, and Akt was significantly attenuated in liver, but not in skeletal muscle, of L-iNOS-Tg mice relative to WT mice without changes in insulin receptor phosphorylation. Moreover, liver-specific iNOS expression abrogated insulin-stimulated phosphorylation of glycogen synthase kinase-3β, forkhead box O1, and mTOR (mammalian target of rapamycin), endogenous substrates of Akt, along with increased S-nitrosylation of Akt relative to WT mice. However, the expression of insulin receptor, IRS-1, IRS-2, Akt, glycogen synthase kinase-3β, forkhead box O1, protein-tyrosine phosphatase-1B, PTEN (phosphatase and tensin homolog), and p85 phosphatidylinositol 3-kinase was not altered by iNOS transgene. Hyperglycemia was associated with elevated glycogen phosphorylase activity and decreased glycogen synthase activity in the liver of L-iNOS-Tg mice, whereas phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and proliferator-activated receptor γ coactivator-1α expression were not altered. These results clearly indicate that selective expression of iNOS in liver causes hepatic insulin resistance along with deranged insulin signaling, leading to hyperglycemia and hyperinsulinemia. Our data highlight a critical role for iNOS in the development of hepatic insulin resistance and hyperglycemia.

Genistein and daidzein repress adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via Wnt/β-catenin signalling or lipolysis.

Objectives:  One aspect of the effects of isoflavones against fat deposition might be at least associated with the mechanism by which Wnt/β‐catenin signalling inhibits adipocyte differentiation. However, it remains completely unknown as to whether isoflavones might influence Wnt signalling during commitment of pluripotent mesenchymal stem cells (MSCs) to adipose lineages. In the present study, we have investigated the mechanisms underlying effects of genistein and daidzein, the major soy isoflavones, on anti‐adipogenic Wnt/β‐catenin signalling.

The global epidemiology of chronic cough in adults: a systematic review and meta-analysis

Cough is an essential defence mechanism [1]. However, chronic cough is a significant cause of morbidity, seriously impairing quality of life [2]. Previously, chronic cough was considered a consequence of various diseases, such as asthma/eosinophilic bronchitis, rhinitis and gastro-oesophageal acid reflux disease [3, 4]. Recent evidence, however, suggests that chronic cough is a clinical syndrome with distinct intrinsic pathophysiology characterised by neuronal hypersensitivity [5–7]. Here, we estimated the worldwide epidemiological burden of chronic cough irrespective of putative diagnosis in general adult populations using a comprehensive systematic literature review. Chronic cough has a high global epidemiological burden. A standard definition would facilitate further studies. http://ow.ly/HPCnw

Association between obesity and asthma in the elderly population: potential roles of abdominal subcutaneous adiposity and sarcopenia

BACKGROUND Obesity is a significant risk factor for asthma; however, the association of asthma with obesity has rarely been studied in the elderly population. The role of central obesity has been suggested as a link between the 2 entities but has not been comprehensively studied in elderly populations. OBJECTIVE To investigate the mechanisms of association between obesity and asthma in the elderly population. METHODS This cross-sectional analysis included 994 participants (aged ≥65 years) in the Korean Longitudinal Study on Health and Aging. Asthma was defined by using questionnaires. Spirometry and chest radiography were performed to exclude asthma-mimicking conditions. Measurements of abdominal subcutaneous and visceral fat were calculated by computed tomography of the abdomen, and regional body compositions were measured by dual energy X-ray absorptiometry. Biochemical parameters were also measured. RESULTS The prevalence of asthma was 5.4%. The study population had a mean body mass index (BMI) of 24.0. Multivariate logistic regression tests revealed that the risk of asthma increased in proportion to an increase in BMI or abdominal subcutaneous adiposity. However, no association was found with visceral adiposity, serum adiponectin levels, or serum vitamin D levels. The dual energy X-ray absorptiometry-measured appendicular fat-free mass index was inversely related to asthma among patients with a BMI of 25.0 or greater. CONCLUSION Our findings suggest that the relationships between obesity and asthma in the elderly population may be mediated by factors such as abdominal subcutaneous adiposity and sarcopenia. These associations warrant further investigations to identify their potential roles.

Anaphylaxis to iodinated contrast media: clinical characteristics related with development of anaphylactic shock.

Objective Anaphylaxis is the most severe form of radiocontrast media (RCM) induced hypersensitivity and can be life-threatening if profound hypotension is combined. With increased use of iodine based RCM, related hypersensitivity is rapidly growing. However, the clinical characteristics and risk factors of RCM induced anaphylaxis accompanied by hypotension (anaphylactic shock) are not clearly defined. This study was performed to investigate the risk factors of RCM induced anaphylactic shock and the clinical value of RCM skin testing to identify causative agents in affected patients. Methods We analyzed the data of RCM induced anaphylaxis monitored by an inhospital pharmacovigilance center at a tertiary teaching hospital from January 2005 to December 2012 and compared the clinical features and skin test results according to the accompanying hypotension. Results Among total of 104 cases of RCM induced anaphylaxis, 34.6% of patients, developed anaphylaxis on their first exposure to RCM. Anaphylactic patients presenting with shock were older (57.4 vs. 50.1 years, p = 0.026) and had a history of more frequently exposure to RCM (5.1±7.8 vs. 1.9±3.3, p = 0.004) compared to those without hypotension. Among RCMs, hypotension was more frequent in anaphylaxis related to iopromide compared to other agents (85.0% vs. 61.4%, p = 0.011). Skin tests were performed in 51 patients after development of RCM induced anaphylaxis. Overall skin test positivity to RCM was 64.7% and 81.8% in patients with anaphylactic shock. Conclusion RCM induced anaphylactic shock is related to multiple exposures to RCM and most patients showed skin test positivity to RCM.

Therapeutic Effects of Fermented Red Ginseng in Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Study

Purpose Allergic rhinitis is clinically defined as a disorder of the nose induced by IgE mediated inflammation after allergen exposure of the nasal mucosa. Many reports have stated that Panax ginseng and fermented red ginseng have anti-inflammatory effects, especially against Th2-type inflammation. This study was conducted to evaluate the therapeutic effects of fermented red ginseng in allergic rhinitis. Methods In this 4-week, double-blind, placebo-controlled study, 59 patients with persistent perennial allergic rhinitis were randomly divided into two groups: those receiving fermented red ginseng tablets (experimental group) and those receiving placebo (control group). The primary efficacy variable was the total nasal symptom score (TNSS; rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were the Rhinitis Quality of Life (RQoL) score and skin reactivity to inhalant allergens, as determined by the skin prick test. Results There was no significant difference in the TNSS score and TNSS duration score between the experimental and placebo groups in weeks 1, 2, 3, or 4. For nasal congestion, fermented red ginseng was significantly effective (P<0.005), while placebo caused no change. The activity and emotion of RQoL improved markedly secondary to treatment with fermented red ginseng (P<0.05), while placebo caused no change. Additionally, fermented red ginseng reduced skin reactivity to sensitized perennial allergens (P<0.05). Fermented red ginseng was well tolerated. Conclusions Fermented red ginseng improved nasal congestion symptoms and RQoL in patients with perennial allergic rhinitis.

An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.

Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.

Cough in the Elderly Population: Relationships with Multiple Comorbidity

Background The epidemiology of cough in the elderly population has not been studied comprehensively. The present study aimed to investigate the epidemiology of cough in a community elderly population, particularly in relation with their comorbidity. Methods A cross-sectional analysis was performed using a baseline dataset from the Korean Longitudinal Study on Health and Aging, a community-based elderly population cohort study. Three types of cough (frequent cough, chronic persistent cough, and nocturnal cough) were defined using questionnaires. Comorbidity was examined using a structured questionnaire. Health-related quality of life was assessed using the Short Form 36 questionnaire. Results The prevalence was 9.3% for frequent cough, 4.6% for chronic persistent cough, and 7.3% for nocturnal cough. In multivariate logistic regression analyses, smoking, asthma and allergic rhinitis were found to be risk factors for cough in the elderly. Interestingly, among comorbidities, constipation and uncontrolled diabetes mellitus (HbA1c ≥ 8%) were also found to have positive associations with elderly cough. In the Short Form 36 scores, chronic persistent cough was independently related to impairment of quality of life, predominantly in the mental component. Conclusions Cough has a high prevalence and is detrimental to quality of life in the elderly. Associations with smoking, asthma and rhinitis confirmed previous findings in younger populations. Previously unrecognised relationships with constipation and uncontrolled diabetes mellitus suggested the multi-faceted nature of cough in the elderly.

Hepatitis B Virus X Protein Regulates Hepatic Glucose Homeostasis via Activation of Inducible Nitric Oxide Synthase

Dysregulation of liver functions leads to insulin resistance causing type 2 diabetes mellitus and is often found in chronic liver diseases. However, the mechanisms of hepatic dysfunction leading to hepatic metabolic disorder are still poorly understood in chronic liver diseases. The current work investigated the role of hepatitis B virus X protein (HBx) in regulating glucose metabolism. We studied HBx-overexpressing (HBxTg) mice and HBxTg mice lacking inducible nitric oxide synthase (iNOS). Here we show that gene expressions of the key gluconeogenic enzymes were significantly increased in HepG2 cells expressing HBx (HepG2-HBx) and in non-tumor liver tissues of hepatitis B virus patients with high levels of HBx expression. In the liver of HBxTg mice, the expressions of gluconeogenic genes were also elevated, leading to hyperglycemia by increasing hepatic glucose production. However, this effect was insufficient to cause systemic insulin resistance. Importantly, the actions of HBx on hepatic glucose metabolism are thought to be mediated via iNOS signaling, as evidenced by the fact that deficiency of iNOS restored HBx-induced hyperglycemia by suppressing the gene expression of gluconeogenic enzymes. Treatment of HepG2-HBx cells with nitric oxide (NO) caused a significant increase in the expression of gluconeogenic genes, but JNK1 inhibition was completely normalized. Furthermore, hyperactivation of JNK1 in the liver of HBxTg mice was also suppressed in the absence of iNOS, indicating the critical role for JNK in the mutual regulation of HBx- and iNOS-mediated glucose metabolism. These findings establish a novel mechanism of HBx-driven hepatic metabolic disorder that is modulated by iNOS-mediated activation of JNK.