• The Korean Journal of Physiology
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• v.3 no.2
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• pp.25-31
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• 1969

Effects of graded increase of positive lung inflation upon heart rates and arterial blood pressure were observed in the anesthetized dogs to analyze the mechanical and neural regulatory factor in response to the positive inflation of the lung. The results obtained were summarized as followings: 1) When the low grade of positive lung inflation was employed under the mild to moderate anesthesia, central venous pressure was linearly increased while heart rate was decreased. After bilateral vagotomy, central venous pressure was obviously increased while heart rate was constant. 2) When the high degree of positive lung inflation was employed, changes of central venous pressure and heart rate were not significant. 3) The low grade of intrapulmonary pressure increase caused reflex tachycardia in phase 2 and overshooting in phase 4 in response to the systemic arterial blood pressure change. 4) On the other hand, the high degree of intrapulmonary pressure increase caused paradoxical bradycardia in phase 2 and lack of overshooting in phase 4 in response to the systemic arterial blood pressure change. 5) It may be noted that the experimental model employed in the present study is a useful tool to evaluate and analyze the neural and mechanical regulatory factor in response to the graded increase of the positive lung inflation.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.27-34
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• 2014

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$) and 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular $Ca^{2+}$ influx via phospholipase $C{\gamma}1$ ($PLC{\gamma}1$) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum $LTC_4$, $PGD_2$, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

• Molecules and Cells
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• v.39 no.10
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• pp.728-733
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• 2016

Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models. The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously. In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs. Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs). Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs. Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection. The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14. A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs. Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection. These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke. These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.

• Journal of Preventive Medicine and Public Health
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• v.53 no.2
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• pp.82-88
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• 2020

Objectives: The objective of this study was to identify individual and institutional factors associated with the prescription of systemic steroids in patients with acute respiratory infections and to investigate the role of a policy measure aimed to reduce inappropriate prescriptions. Methods: We used data from the National Health Insurance Service-National Sample Cohort from 2006 to 2015 and focused on episodes of acute respiratory infection. Descriptive analysis and multiple logistic regression analysis were performed to identify individual-level and institution-level factors associated with the prescription of systemic steroids. In addition, steroid prescription rates were compared with antibiotic prescription rates to assess their serial trends in relation to Health Insurance Review and Assessment Service (HIRA) Prescription Appropriateness Evaluation policy. Results: Among a total of 9 460 552 episodes of respiratory infection, the steroid prescription rate was 6.8%. Defined daily doses/1000 persons/d of steroid increased gradually until 2009, but rose sharply since 2010. The steroid prescription rate was higher among ear, nose and throat specialties (13.0%) than other specialties, and in hospitals (8.0%) than in tertiary hospitals (3.0%) and other types of institutions. Following a prolonged reduction in the steroid prescription rate, this rate increased since the HIRA Prescription Appropriateness Evaluation dropped steroids from its list of evaluation items in 2009. Such a trend reversal was not observed for the prescription rate of antibiotics, which continue to be on the HIRA Prescription Appropriateness Evaluation list. Conclusions: Specialty and type of institution are important correlates of steroid prescriptions in cases of acute respiratory infection. Steroid prescriptions can also be influenced by policy measures, such as the HIRA Prescription Appropriateness Evaluation policy.

• BMB Reports
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• v.52 no.4
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• pp.259-264
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• 2019

Social requirements are needed for living in an aging society and individual longevity. Among them, improved health and medical cares, appropriate for an aging society are strongly demanded. Human cord blood-derived plasma (hUCP) has recently emerged for its unique anti-aging effects. In this study, we investigated brain rejuvenation, particularly olfactory function, that could be achieved by a systemic administration of young blood and its underlying mechanisms. Older than 24-month-old mice were used as an aged group and administered with intravenous injection of hUCP repetitively, eight times. Anti-aging effect of hUCP on olfactory function was evaluated by buried food finding test. To investigate the mode of action of hUCP, brain, serum and spleen of mice were collected for further ex vivo analyses. Systemic injection of hUCP improved aging-associated olfactory deficits, reducing time for finding food. In the brain, although an infiltration of activated microglia and its expression of cathepsin S remarkably decreased, significant changes of proinflammatory factors were not detected. Conversely, peripheral immune balance distinctly switched from predominance of Type 1 helper T (Th1) cells to alternative regulatory T cells (Tregs). These findings indicate that systemic administration of hUCP attenuates age-related neuroinflammation and subsequent olfactory dysfunction by modulating peripheral immune balance toward Treg cells, suggesting another therapeutic function and mechanism of hUCP administration.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.287-295
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• 2022

Staphylococcus aureus (S. aureus) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S. aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ⁺/IL-4⁺ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V⁺/7-AAD⁺ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163⁺ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.293.2-294
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• 2003

Topical buccal therapy with steroid anti-inflammatory drugs is based on the concept that a high activity of steroids can be produced at the site of administration and, at the same time, the degree of systemic side effects can be minimized or avoided. In this study we developed a new formulation consisting of a mucoadhesive bead for buccal administration of glucocorticoids. (omitted)

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.54-55
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• 2006

Polymeric micelles, supramolecular assemblies of block copolymers, are useful nanocarriers for the systemic delivery of drugs and genes. Recently, novel polymeric micelles with various functions such as the targetability and stimuli-sensitivity have been emerged as promising carriers that enhance the efficacy of drugs and genes with minimal side effects. This presentation focuses our recent approach to the preparation of functional block copolymers that are useful for constructing smart micellar delivery systems in advanced therapeutics, including chemo-gene therapy. Particular emphasis is placed on the characteristic behaviors of intracellular environment-sensitive micelles that selectively exert drug activity and gene expression in live cells.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.529-538
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• 2002

Background : Many clinicians are reluctant to prescribe systemic corticosteroids to manage an asthmatic attack because of many complications such as osteoporosis, cushing's syndrome, diabetes, hypertension and bleeding tendency. The use of nebulized budesonide may be of value in some infants, old men, and in particular adult asthmatic patients who complain of severe dyspnea. A clinical validation and steroid-sparing effect of nebulized budesonide in asthmatic adults and COPD were evaluated, and the short-term effects of budesonide use on the HPA axis were assessed. Materials and Methods : Study A was prospectively done with 41 patients diagnosed with pure asthma and 30 patients diagnosed with COPD (including asthmatic component) in Soonchunhyang Hospital, Chunan from June. 2000 to Sep. 2001. They were treated with nebulized budesonide including systemic steroids (Group 1), a budesonide tubuhaler including a systemic steroid (Group 2), or only the systemic steroid(Group 3). The peak flow rate, arterial blood gas in room air, pulmonary function test, symptom scoring, steroid amount and hospital stay were analyzed. Study B was conducted with 19 patients to evaluate the short-term effects on the HPA axis of treatment with nebulized budesonide 1mg twice daily and a budesonide turbuhaler 5 puffs twice daily. The adrenal function was assessed prior to budesonide inhalation and after 7 days of budesonide inhalation. Results : In the pure asthmatic patients, the mean value of the symptoms (dyspnea, wheezing, cough, night asthma) or the arterial BGAs, total amounts of steroid or hospital stay and the difference in the results of the pulmonary function tests or peak expiratory flow rate were similar in the three groups. In COPD with an asthmatic component, there were no significant differences among the three groups. Although nebulized budesonide suppressed HPA function,(p=0.006) the HPA responses from the nebulized budesonide and turbuhaler budesonide were similar (p=0.288) Conclusion : This result suggests that systemic steroid should only be made available for acute asthmatic patients irrespective of the inhaled budesonides. Nebulized budesonide at the therapeutic dose has similar effects on the HPA axis compared to that of turbuhaler budesonide.

• Journal of Photoscience
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• v.3 no.1
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• pp.29-31
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• 1996

Psoralens are metabolized in the liver and thus can produce liver damage in laboratory animals when given in excessive doses. However, in humans, reports of the effects of psoralens on liver functions during photochemotherapy have been contradictory. We studied 311 patients t o observe the effects of various phototoxic drugs: 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 4,5,8-trimethylpsoralen (TMP)-on liver function during photochemotherapy. Of the 311 patients, only seven had transient elevations of transaminases. Incidence of hepatotoxicity of 8-MOP, TMP and 5-MOP showed 0.6%, 6% and 3%, respectively. Although the effects of psoralens on liver functions during photochemotherapy have been contradictory in humans and there have been few cases showing transient elevated values of liver transaminases during photochemotherapy, it is advisable to obtain serial liver function tests before and during photochemotherapy.