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Objective@#Cognitive reserve (CR) protects against cognitive decline by utilizing functional connectivity (FC) in the brain, such as the default mode network (DMN). We studied whether CR in individuals with predementia would correlate with better cognition and increased DMN FC in the resting brain. @*Methods@#Fifty-four participants with subjective cognitive decline or mild cognitive impairment completed the Cognitive Reserve Index (CRI) questionnaire, and underwent a comprehensive neuropsychological test battery and resting state functional magnetic resonance imaging. Correlation and regression analyses for clinical variables and seed-to-voxel analyses of CR-related FC in the DMN were conducted. @*Results@#CRI total (β=0.42, p=0.001), education (β=0.39, p=0.001), and leisure time (β=0.33, p=0.009) predicted the MiniMental State Examination. The CRI education predicted verbal memory recall (β=0.32, p=0.017), confrontational naming (β=0.57, p<0.001), and phonemic fluency (β=0.43, p=0.004). In the DMN in the resting brain, the CRI total correlated with increased FC, based on the posterior cingulate to both lateral parietal cortices. @*Conclusion@#In individuals with predementia, comprehensive CR correlated with an enhanced network in the DMN in the resting state. These results may support the neural correlate of CR during the initial stage of cognitive decline.
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Background@#We analyzed hemoglobin A1c (HbA1c) levels and various lung function test results in healthy individuals after a 6-year follow-up period to explore the influence of lung function changes on glycemic control. @*Methods@#Subjects whose HbA1c levels did not qualify as diabetes mellitus (DM) and who had at least two consecutive lung function tests were selected among the people who visited a health promotion center. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV/FVC ratio, and forced expiratory flow 25% to 75% (FEF25%−75%), were divided into four groups based on their baseline quantiles. To evaluate future DM onset risk in relation to lung function changes, the correlation between baseline HbA1c levels and changes in lung function parameters after a 6-year follow-up period was analyzed. @*Results@#Overall, 17,568 individuals were included; 0.9% of the subjects were diagnosed with DM. The individuals included in the quartile with FEV1/FVC ratio values of 78% to 82% had lower risk of DM than those in the quartile with FEV1/FVC ratio values of ≥86% after adjusting for age, sex, and body mass index (P=0.04). Baseline percent predicted FEV1, FVC, FEV1/FVC ratio, and FEF25%−75%, and differences in the FEV1/FVC ratio or FEF25%−75%, showed negative linear correlations with baseline HbA1c levels. @*Conclusion@#Healthy subjects with FEV1/FVC ratio values between 78% and 82% had 40% lower risk for future DM. Smaller differences and lower baseline FEV1/FVC ratio or FEF25%−75% values were associated with higher baseline HbA1c levels. These findings suggest that airflow limitation affects systemic glucose control and that the FEV1/FVC ratio could be one of the factors predicting future DM risk in healthy individuals.
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Background/Aims@#Current asthma therapies remain unsatisfactory for controlling airway remodelling in asthma. MicroRNA-21 is a key player in asthma pathogenesis, but the molecular mechanisms underlying its effects on airway remodelling are not completely understood. We investigated the effects of inhibition of microRNA-21 on allergic airway inflammation and remodelling. @*Methods@#Female BALB/c mice were divided into four groups: control, ovalbumin-sensitized and -challenged for 3 months, microRNA-negative control-treated ovalbumin-treated, and microRNA-21 inhibitor-treated ovalbumin-treated groups. Parameters related to airway remodelling, cytokine production, airway inflammation, and airway hyperresponsiveness were compared between groups. Human bronchial smooth muscle cells were used in a mechanism study. @*Results@#In this asthma model, ovalbumin-sensitized and -challenged mice exhibited allergic airway inf lammation and airway remodelling. MicroRNA-21 inhibitor-treated mice had fewer inflammatory cells, lower TH2 cytokine production, and suppressed parameters related to remodelling such as goblet cell hyperplasia, collagen deposition, hydroxyproline content, and expression of smooth muscle actin. Inhibition of microRNA-21 decreased transforming growth factor β1 expression and induced Smad7 expression in lung tissue. In human bronchial smooth muscle cells stimulated with transforming growth factor β1, microRNA-21 inhibition upregulated Smad7 expression and decreased markers of airway remodelling. @*Conclusions@#Inhibition of microRNA-21 had both anti-inflammatory and anti-remodelling effects in this model of ovalbumin-induced chronic asthma. Our data suggest that the microRNA-21–transforming growth factor β1–Smad7 axis modulates the pathogenesis of ovalbumin-induced chronic asthma and in human bronchial smooth muscle cells. MicroRNA-21 inhibitors may be a novel therapeutic target in patients with allergic asthma, especially those with airway remodelling.
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Background/Aims@#Current asthma therapies remain unsatisfactory for controlling airway remodelling in asthma. MicroRNA-21 is a key player in asthma pathogenesis, but the molecular mechanisms underlying its effects on airway remodelling are not completely understood. We investigated the effects of inhibition of microRNA-21 on allergic airway inflammation and remodelling. @*Methods@#Female BALB/c mice were divided into four groups: control, ovalbumin-sensitized and -challenged for 3 months, microRNA-negative control-treated ovalbumin-treated, and microRNA-21 inhibitor-treated ovalbumin-treated groups. Parameters related to airway remodelling, cytokine production, airway inflammation, and airway hyperresponsiveness were compared between groups. Human bronchial smooth muscle cells were used in a mechanism study. @*Results@#In this asthma model, ovalbumin-sensitized and -challenged mice exhibited allergic airway inf lammation and airway remodelling. MicroRNA-21 inhibitor-treated mice had fewer inflammatory cells, lower TH2 cytokine production, and suppressed parameters related to remodelling such as goblet cell hyperplasia, collagen deposition, hydroxyproline content, and expression of smooth muscle actin. Inhibition of microRNA-21 decreased transforming growth factor β1 expression and induced Smad7 expression in lung tissue. In human bronchial smooth muscle cells stimulated with transforming growth factor β1, microRNA-21 inhibition upregulated Smad7 expression and decreased markers of airway remodelling. @*Conclusions@#Inhibition of microRNA-21 had both anti-inflammatory and anti-remodelling effects in this model of ovalbumin-induced chronic asthma. Our data suggest that the microRNA-21–transforming growth factor β1–Smad7 axis modulates the pathogenesis of ovalbumin-induced chronic asthma and in human bronchial smooth muscle cells. MicroRNA-21 inhibitors may be a novel therapeutic target in patients with allergic asthma, especially those with airway remodelling.
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Background@#Bats have been considered natural reservoirs for several pathogenic human coronaviruses (CoVs) in the last two decades. Recently, a bat CoV was detected in the Republic of Korea; its entire genome was sequenced and reported to be genetically similar to that of the severe acute respiratory syndrome CoV (SARS-CoV). @*Objectives@#The objective of this study was to compare the genetic sequences of SARSCoV, SARS-CoV-2, and the two Korean bat CoV strains 16BO133 and B15-21, to estimate the likelihood of an interaction between the Korean bat CoVs and the human angiotensinconverting enzyme 2 (ACE2) receptor. @*Methods@#The phylogenetic analysis was conducted with the maximum-likelihood (ML) method using MEGA 7 software. The Korean bat CoVs receptor binding domain (RBD) of the spike protein was analyzed by comparative homology modeling using the SWISS-MODEL server. The binding energies of the complexes were calculated using PRODIGY and MM/GBGA. @*Results@#Phylogenetic analyses of the entire RNA-dependent RNA polymerase, spike regions, and the complete genome revealed that the Korean CoVs, along with SARS-CoV and SARSCoV-2, belong to the subgenus Sarbecovirus, within BetaCoVs. However, the two Korean CoVs were distinct from SARS-CoV-2. Specifically, the spike gene of the Korean CoVs, which is involved in host infection, differed from that of SARS-CoV-2, showing only 66.8%–67.0% nucleotide homology and presented deletions within the RBD, particularly within regions critical for cross-species transmission and that mediate interaction with ACE2. Binding free energy calculation revealed that the binding affinity of Korean bat CoV RBD to hACE2 was drastically lower than that of SARS-CoV and SARS-CoV-2. @*Conclusions@#These results suggest that Korean bat CoVs are unlikely to bind to the human ACE2 receptor.
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Background/Aims@#Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2)+ CD4+ Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma. @*Methods@#BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR). @*Results@#Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment. @*Conclusions@#These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma.
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Background@#Studies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (TH2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed. @*Methods@#Using a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow-derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing. @*Results@#Ovalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in TH2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and TH2 cytokine levels. @*Conclusion@#The results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.
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BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.
Subject(s)
Aged , Animals , Female , Humans , Mice , Actins , Airway Remodeling , Asthma , Eosinophils , Hydroxyproline , Interleukin-13 , Interleukin-5 , Interleukins , Ovalbumin , Ovum , Pneumonia , Receptors, Muscarinic , Tiotropium BromideABSTRACT
PURPOSE: In the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO. METHODS: SIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12–75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β2-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/µL. This subgroup analysis evaluated Korean patients from this group. RESULTS: Of 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/µL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13–0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06–0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039–0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143–0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (−0.27 [95% CI, −0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, −0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.
Subject(s)
Humans , Arm , Asthma , Eosinophils , Forced Expiratory Volume , Korea , Lung , Receptors, Interleukin-5ABSTRACT
Cervical plexus blocks (CPBs) have been used in various head and neck surgeries to provide adequate anesthesia and/or analgesia; however, the block is performed in a narrow space in the region of the neck that contains many sensitive structures, multiple fascial layers, and complicated innervation. Since the intermediate CPB was introduced in addition to superficial and deep CPBs in 2004, there has been some confusion regarding the nomenclature and definition of CPBs, particularly the intermediate CPB. Additionally, as the role of ultrasound in the head and neck region has expanded, CPBs can be performed more safely and accurately under ultrasound guidance. In this review, the authors will describe the methods, including ultrasound-guided techniques, and clinical applications of conventional deep and superficial CPBs; in addition, the authors will discuss the controversial issues regarding intermediate CPBs, including nomenclature and associated potential adverse effects that may often be neglected, focusing on the anatomy of the cervical fascial layers and cervical plexus. Finally, the authors will attempt to refine the classification of CPB methods based on the target compartments, which can be easily identified under ultrasound guidance, with consideration of the effects of each method of CPB.
Subject(s)
Airway Obstruction , Analgesia , Anesthesia , Cervical Plexus Block , Cervical Plexus , Classification , Head , Methods , Neck , UltrasonographyABSTRACT
BACKGROUND/AIMS: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. METHODS: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. RESULTS: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. CONCLUSIONS: These results suggest that the IL-17–leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.
Subject(s)
Animals , Humans , Mice , Adipokines , Adipose Tissue , Asthma , Bronchoalveolar Lavage Fluid , Cell Differentiation , Diet, High-Fat , Goblet Cells , Inflammation , Interleukin-17 , Obesity , Ovalbumin , Ovum , Oxidoreductases , Pravastatin , Respiratory Hypersensitivity , SpleenABSTRACT
PURPOSE: Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. There is emerging interest in the involvement of the transient receptor potential vanilloid 1 (TRPV1) channel in the pathophysiology of asthma. This study examined whether TRPV1 antagonism alleviates asthma features in a murine model of chronic asthma. METHODS: BALB/c mice were sensitized to and challenged by ovalbumin to develop chronic asthma. Capsazepine (TRPV1 antagonist) or TRPV1 small interfering RNA (siRNA) was administered in the treatment group to evaluate the effect of TPV1 antagonism on AHR, airway inflammation, and remodeling. RESULTS: The mice displayed increased AHR, airway inflammation, and remodeling. Treatment with capsazepine or TRPV1 siRNA reduced AHR to methacholine and airway inflammation. Type 2 T helper (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13) were reduced and epithelial cell-derived cytokines (thymic stromal lymphopoietin [TSLP], IL-33, and IL-25), which regulate Th2 cytokine-associated inflammation, were also reduced. Airway remodeling characterized by goblet cell hyperplasia, increased α-smooth muscle action, and collagen deposition was also alleviated by both treatments. CONCLUSIONS: Treatment directed at TRPV1 significantly alleviated AHR, airway inflammation, and remodeling in a chronic asthma murine model. The TRPV1 receptor can be a potential drug target for chronic bronchial asthma.
Subject(s)
Animals , Mice , Airway Remodeling , Asthma , Collagen , Cytokines , Goblet Cells , Hyperplasia , Inflammation , Interleukin-33 , Interleukin-5 , Methacholine Chloride , Ovalbumin , RNA, Small InterferingABSTRACT
PURPOSE: Asthma is a chronic airway disease characterized by airway remodeling, leading to a progressive decline in lung function. Therapeutic agents that attenuate airway remodeling can complement the limited effects of traditional glucocorticoids. In this study, we investigated the effect of resveratrol on allergic airway inflammation and remodeling in a murine model of chronic bronchial asthma. METHODS: Peribronchial smooth muscle thickening that developed in mice challenged with a 3-month repeated exposure to ovalbumin (OVA) was used to study airway remodeling. Oral resveratrol was administered daily during the OVA challenge. The expression of TGF-β1/Smad signaling proteins and downstream mesenchymal markers in the presence or absence of resveratrol was examined in bronchial epithelial cells. RESULTS: OVA sensitization and chronic challenge increased airway hyperresponsiveness, inflammation, goblet cell hyperplasia, α-smooth muscle actin (SMA), and collagen deposition. Resveratrol effectively suppressed OVA-induced airway inflammation and remodeling. The expression of TGF-β1/phosphorylated Smad2/3 was increased in the lung tissues of OVA-challenged mice but effectively inhibited by resveratrol. In bronchial epithelial cells, the TGF-β1-induced expression of the mesenchymal markers snail, slug, vimentin, and α-SMA was suppressed by resveratrol treatment. CONCLUSIONS: Resveratrol effectively ameliorated both airway inflammation and airway structural changes in a mouse model of bronchial asthma. These effects were mediated by decreased TGF-β1 expression, in turn suppressing TGF-β1/Smad signaling and the epithelial-mesenchymal transition process. Our results demonstrate the potential benefits of resveratrol for the treatment of airway remodeling associated with bronchial asthma.
Subject(s)
Animals , Mice , Actins , Airway Remodeling , Asthma , Collagen , Complement System Proteins , Epithelial Cells , Epithelial-Mesenchymal Transition , Gastropoda , Glucocorticoids , Goblet Cells , Hyperplasia , Inflammation , Lung , Muscle, Smooth , Ovalbumin , Ovum , Snails , VimentinABSTRACT
Tuberculosis (TB) is associated with an increased risk of chronic lung impairment. The aim of this study was to compare the clinical characteristics and lung functions according to definition of past TB. We used the population-based, Korea National Health and Nutrition Examination Survey (KNHANES) (2008–2012) to analyze 13,522 subjects age 40 years or older who underwent spirometry and chest X-ray (CXR). Subjects with TB lesions on CXR (with or without a history of TB) were older, more likely to be male, ever smokers, and of low socioeconomic status than subjects with only a history of TB or without evidence of TB. Airflow obstruction (AFO) was associated with only a history of TB (odds ratio [OR] 1.53, 95% confidence interval [CI] 0.95–2.46), only TB lesion on CXR (OR 2.37, 95% CI 1.80–3.12), and both a history and TB lesions on CXR (OR 4.47, 95% CI 3.07–6.51) after adjustment for gender, age, body mass index, education, income, and smoking amount (P for trend < 0.001). Spirometric restriction was associated with only a history of TB (OR 1.29, 95% CI 0.80–2.08), only TB lesions on CXR (OR 2.03, 95% CI 1.49–2.76), and both a history and TB lesions on CXR (OR 2.65, 95% CI 1.74–4.05) after adjustment for the above variables (P for trend < 0.001). How to define past TB in population study affects the magnitude of association between past TB and respiratory dysfunction. Without considering TB lesions on CXR, the association between TB and respiratory dysfunction could be underestimated.
Subject(s)
Humans , Male , Body Mass Index , Education , Korea , Lung , Lung Diseases , Mass Chest X-Ray , Nutrition Surveys , Smoke , Smoking , Social Class , Spirometry , Thorax , Tuberculosis , Tuberculosis, PulmonaryABSTRACT
BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.
Subject(s)
Adult , Humans , Dyspnea , Hematologic Neoplasms , Immunocompromised Host , Logistic Models , Organ Transplantation , Pneumocystis carinii , Pneumocystis , Pneumonia , Pneumonia, Pneumocystis , Polymerase Chain Reaction , Prevalence , Retrospective Studies , Risk Factors , TransplantsABSTRACT
BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.
Subject(s)
Adult , Humans , Dyspnea , Hematologic Neoplasms , Immunocompromised Host , Logistic Models , Organ Transplantation , Pneumocystis carinii , Pneumocystis , Pneumonia , Pneumonia, Pneumocystis , Polymerase Chain Reaction , Prevalence , Retrospective Studies , Risk Factors , TransplantsABSTRACT
BACKGROUND/AIMS: Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition. RESULTS: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and NF-kappaB. CONCLUSIONS: These results suggest that intranasal administration of rosiglitazone can prevent not only air way inf lammation but also air way remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and NF-kappaB pathways.
Subject(s)
Animals , Female , Actins/metabolism , Administration, Inhalation , Airway Remodeling/drug effects , Anti-Asthmatic Agents/administration & dosage , Asthma/chemically induced , Chronic Disease , Collagen/metabolism , Disease Models, Animal , Lung/drug effects , Mice, Inbred BALB C , NF-kappa B/metabolism , Ovalbumin , PPAR gamma/agonists , Pneumonia/chemically induced , Pulmonary Eosinophilia/chemically induced , Signal Transduction/drug effects , Thiazolidinediones/administration & dosage , Toll-Like Receptor 4/metabolismABSTRACT
BACKGROUND: Changes in pulse pressure (PP) may alter the morphology of arterial pressure waveforms, thereby affecting the accuracy of cardiac output (CO) measurements derived from such waveforms. This study evaluated the influence of PP on the accuracy of FloTrac/Vigileo™ system-measured CO (APCO). Pulmonary artery catheter (PAC) measured stat mode CO (SCO) is used as a reference standard. METHODS: Hemodynamic variables were measured at various time points in 24 patients. APCO and SCO were compared using Bland-Altman analysis of the overall data pairs. The data pairs were divided into a low PP group and a high PP group, and subgroup analysis was conducted. RESULTS: The mean APCO (5.3 ± 1.7 L/min) was higher than the mean SCO (5.1 ± 1.6 L/min) for all data pairs (P < 0.001). The Bland-Altman analysis revealed an overall percentage error of 41.7% between the APCO and SCO, which exceeds a 30% limit of agreement. There was a significant relationship between PP and the difference between APCO and SCO (P = 0.031, R = 0.151). In subgroup analysis, APCO and SCO showed reasonable agreement in the low PP group, with a percentage error of 28.2%, but decreased agreement in the high PP group, with a percentage error of 43.2%. CONCLUSIONS: Changes in PP affect the accuracy of APCO measurements. An acceptable level of agreement between APCO and SCO was observed only in a low range of PP.
Subject(s)
Humans , Arterial Pressure , Blood Pressure , Cardiac Output , Catheters , Hemodynamics , Pulmonary ArteryABSTRACT
PURPOSE: The purpose of this study was to analyze the antimicrobial, antioxidant activity and cytotoxicity of Dendropanax morbifera Léveille extract for assessing whether Dendropanax morbifera Léveille can be used for the development of natural mouthwash and denture cleaning solution. MATERIALS AND METHODS: The extract was obtained from branches of Dendropanax morbifera Léveille. The solvent fractions were acquired by fractionating Dendropanax morbifera Léveille extract using n-hexane, ethyl acetate, chloroform and butanol solvent. Paper disc test was used to evaluate the antimicrobial and antifungal activity of Dendropanax morbifera Léveille extract and solvent fractions against Streptococcus mutans and Candida albicans. The analysis of antioxidant activity was carried out through DPPH radical scavenging assay. The cytotoxicity of Dendropanax morbifera Léveille extract was analyzed through MTT assay using normal human oral keratinocytes. RESULTS: Dendropanax morbifera Léveille extract showed antimicrobial activity against Streptococcus mutans and especially Candida albicans. The solvent fractions of Dendropanax morbifera Léveille showed strong antimicrobial activity against Streptococcus mutans and Candida albicans in n-hexane and butanol solvent fraction, respectively. Dendropanax morbifera Léveille extract also showed outstanding antioxidant activity. Butanol, ethyl acetate, and chloroform solvent fraction of Dendropanax morbifera Léveille tended to have increased antioxidant activity as the concentration increased. Dendropanax morbifera Léveille extract showed high cell survival rate in cytotoxicity test. CONCLUSION: Dendropanax morbifera Léveille extract turned out to have antimicrobial, antioxidant activity and cytophilicity. Based on these results, it is expected that Dendropanax morbifera Léveille is applicable as an ingredient for natural mouthwash and denture cleanser.
Subject(s)
Humans , Candida albicans , Cell Survival , Chloroform , Denture Cleansers , Dentures , Keratinocytes , Streptococcus mutansABSTRACT
BACKGROUND/AIMS: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge. RESULTS: Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly. CONCLUSIONS: These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.