Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.
Acetylation ; Amino Acids ; Citric Acid Cycle ; Diabetes Mellitus, Type 2 ; Fatty Acids ; Glucose ; Glycolysis ; Metabolic Diseases ; Metabolic Networks and Pathways ; Metabolism* ; Mitochondria ; Neurodegenerative Diseases ; Obesity ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphoric Monoester Hydrolases ; Phosphorylation ; Phosphotransferases ; Protein Processing, Post-Translational ; Pyruvate Dehydrogenase Complex* ; Pyruvic Acid*

PURPOSE: Recurrent respiratory tract infection is a common manifestation of primary immunodeficiency disease, and respiratory viruses or bacteria are important triggers of asthma exacerbations. Asthma often coexists with humoral immunodeficiency in adults, and some asthmatics with immunoglobulin (Ig) G subclass deficiency (IgGSCD) suffer from recurrent exacerbations. Although some studies suggest a benefit from Ig replacement, others have failed to support its use. This study aimed to assess the effect of Ig replacement on asthma exacerbation caused by respiratory infection as well as the asthma control status of adult asthmatics with IgGSCD. METHODS: This is a multi-center, open-label study of adult asthmatics with IgGSCD. All patients received monthly intravenous immunoglobulin (IVIG) for 6 months and were evaluated regarding asthma exacerbation related to infection, asthma control status, quality of life, and lung function before and after IVIG infusion. RESULTS: A total of 30 patients were enrolled, and 24 completed the study. Most of the patients had a moderate degree of asthma severity with partly (52%) or uncontrolled (41%) status at baseline. IVIG significantly reduced the proportion of patients with asthma exacerbations, lowered the number of respiratory infections, and improved asthma control status, compared to the baseline values (P<0.001). The mean asthma-specific quality of life and asthma control test scores were improved significantly (P=0.009 and P=0.053, respectively); however, there were no significant changes in lung function. CONCLUSIONS: IVIG reduced the frequency of asthma exacerbations and improved asthma control status in adult asthmatics with IgGSCD, suggesting that IVIG could be an effective treatment option in this population.
Adult* ; Asthma* ; Bacteria ; Humans ; Immunoglobulin G* ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Lung ; Quality of Life ; Respiratory Tract Infections

Noncardiac chest pain (NCCP) is one of the most common esophageal symptoms and lacks a clearly defined mechanism. The most common cause of NCCP is gastroesophageal reflux disease (GERD). One of the accepted mechanisms of NCCP in a patient without GERD has been altered visceral sensitivity. Mast cells may play a role in visceral hypersensitivity in irritable bowel syndrome. In this case, a patient with NCCP and dysphagia who was unresponsive to proton pump inhibitor treatment had an increased esophageal mast cell infiltration and responded to 14 days of antihistamine and antileukotriene treatment. We suggest that there may be a relationship between esophageal symptoms such as NCCP and esophageal mast cell infiltration.
Adult ; Chest Pain/*etiology ; Esophageal Diseases/*complications/drug therapy ; Esophagus/cytology/pathology ; Female ; Histamine Antagonists/therapeutic use ; Humans ; Leukotriene Antagonists/therapeutic use ; Mast Cells/metabolism ; Mastocytosis/*complications/drug therapy

Cefotetan is a commonly prescribed second-generation cephalosporin that acts against a wide range of bacteria. However, cefotetan-induced hypersensitivity has rarely been reported. We report 2 cases of cefotetan-induced anaphylaxis with immunologic evaluation. The first case was a 70-year-old asthmatic woman who had dyspnea and hypotension during administration of cefotetan, in which high serum-specific IgE to cefotetan-human serum albumin (HSA) conjugate was detected by enzyme-linked immunosorbent assay. The second case was a 63-year-old asthmatic woman who complained of chest tightness and dyspnea during cefotetan infusion, in which high serum-specific IgG1 and IgG4 with no serum specific IgE to cefotetan-HSA conjugate was detected. The basophil activation test using basophils from the patient showed a significant up-regulation of CD63 with the addition of anti-IgG4 antibody compared with that in non-atopic healthy controls. In conclusion, cefotetan can induce anaphylaxis, which may involve both IgE- and IgG4-mediated responses in the pathogenic mechanism.
Aged ; Anaphylaxis* ; Bacteria ; Basophils ; Cefotetan ; Dyspnea ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hypersensitivity ; Hypotension ; Immunoglobulin E ; Immunoglobulin G ; Middle Aged ; Serum Albumin ; Thorax ; Up-Regulation

PURPOSE: Differences in definitions of the condition, relevant triggers, and the geographical locations of study centers, cause estimates of the prevalence of anaphylaxis to vary. Recent epidemiological data indicate that the incidence of anaphylaxis is rising. METHODS: To investigate the causes and clinical features of anaphylaxis in Korean adults, factors associated with the severity of the condition, and serious outcomes, a retrospective medical record review was performed on adult patients diagnosed with anaphylaxis between 2007 and 2011 in 15 University Hospitals of South Korea. RESULTS: A total of 1,806 cases (52% male, age 16-86 years) were reported. Cutaneous symptoms (84.0%), combined with respiratory (53.9%) and/or cardiovascular (55.4%) symptoms, were the most frequent presentations. Using a recognized grading system, 1,776 cases could be classified as either mild, 340; moderate, 690; or severe, 746. Although eliciting factors varied significantly by age, gender, and regional and seasonal factors, drugs (46.5%; including nonsteroidal anti-inflammatory drugs, antibiotics, and radiocontrast media) were the most common cause of anaphylaxis, followed by foods (24.2%), insect stings (16.4%), exercise (5.9%), and unknown etiology (7.0%). All of age, multi-organ involvement, a history of allergic disease, and drug-induced anaphylaxis, were significant predictors of serious outcomes requiring hospital admission or prolongation of hospital stay. Epinephrine auto-injectors were prescribed for 7.4% of reported cases. CONCLUSIONS: The principal causes of anaphylaxis in Korean adults were drugs, food, and insect stings. Drug-associated anaphylaxis, a history of allergic disease, multi-organ involvement, and older age, were identified as predictors of serious outcomes.
Adult* ; Anaphylaxis* ; Anti-Bacterial Agents ; Epidemiology ; Epinephrine ; Hospitals, University ; Humans ; Incidence ; Insect Bites and Stings ; Korea ; Length of Stay ; Male ; Medical Records ; Prevalence ; Retrospective Studies* ; Seasons

PURPOSE: To investigate whether causes of anaphylaxis vary according to regions and seasons in Korean adults. METHODS: Based on previous retrospective studies of anaphylaxis between 2007 and 2011 at the 15 university hospitals. Regions were classified into 4 groups: region I, Seoul; region II, Gyeonggi; region III, Chungcheong; and region IV, Chonnam and Busan. The cases induced by 5 major allergens including drugs, food, bee sting, radiocontrast media, and exercise, were analyzed in the present study. RESULTS: Among a total of 1,661 cases reported (53% male, 45.9+/-16.0 years), 367 (22.2%), 706 (42.5%), 319 (19.2%), and 269 cases (16.2%) were enrolled in regions I, II, III, and IV, respectively. Of the 5 major allergens, drugs (37.3%) were the most frequently reported, followed by food (25.7%), bee sting (17.9%), radiocontrast media (12.9%), and exercise (6.2%). There was no significant difference in the total occurrence of anaphylaxis in 4 seasons (374 in spring, 460 in summer, 460 in autumn, and 367 in winter). Multiple logistic regression analysis revealed that drug-induced anaphylaxis was significantly associated with the winter season (odds ratio [OR] 1.0 vs. OR 0.597, P<0.05 for spring; OR 1.0 vs. OR 0.481, P<0.01 for summer; OR 1.0 vs. OR 0.653, P<0.05 for autumn). Food-associated anaphylaxis was mainly reported in region I, whereas the frequency of insect sting was relatively higher in regions II, III, and IV than in region I. Older age and female gender were significantly associated with drug-induced anaphylaxis. CONCLUSION: Specific causative allergens of anaphylaxis in adults may vary according to age, gender, region, and season in Korea.
Adult* ; Allergens ; Anaphylaxis* ; Bees ; Bites and Stings ; Busan ; Contrast Media ; Female ; Geographic Locations ; Gyeonggi-do ; Hospitals, University ; Humans ; Insect Bites and Stings ; Jeollanam-do ; Korea ; Logistic Models ; Male ; Retrospective Studies ; Seasons* ; Seoul

The geriatric population is increasing, and asthma severity increases with age. We determined the predictors of asthma control, exacerbation, and the factors that affect asthma-specific quality of life (A-QOL) in elderly asthmatic patients. This was a prospective, multicenter, real-life study for 6 months with stepwise pharmacologic treatment based on the Global Initiative for Asthma (GINA) guideline. A total of 296 asthmatic patients aged > or = 60 yr were recruited from 5 university centers in Korea. The improved-asthma control group was defined as the group of patients who maintained well-controlled or improved disease and the not-improved asthma control group was defined as the remaining patients. Fewer number of medications for comorbidities (2.8 +/- 3.3 in the improved vs. 4.5 +/- 4.4 in the control) and higher physical functioning (PF) scale (89.8 +/- 14.2 in the improved vs. 82.0 +/- 16.4 in the control) were significant predictors in the improved-asthma control group (OR = 0.863, P = 0.004 and OR = 1.028, P = 0.018, respectively). An asthma control test (ACT) score of < or = 19 at baseline was a significant predictor of asthma exacerbation (OR = 3.938, P = 0.048). Asthma duration (F = 5.656, P = 0.018), ACT score (F = 12.237, P = 0.001) at baseline, and the presence of asthma exacerbation (F = 5.565, P = 0.019) were significant determinants of changes in A-QOL. The number of medications for comorbidities and performance status determined by the PF scale may be important parameters for assessing asthma control in elderly asthmatic patients.
Aged ; Aged, 80 and over ; Anti-Asthmatic Agents/*administration & dosage ; Asthma/*diagnosis/epidemiology/*therapy ; Critical Pathways/statistics & numerical data ; Dose-Response Relationship, Drug ; Female ; Geriatric Assessment/*methods/statistics & numerical data ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care)/*methods ; *Quality of Life ; Reproducibility of Results ; Republic of Korea/epidemiology ; Sensitivity and Specificity ; Treatment Outcome

OBJECTIVES: The aim of this study was to investigate the clinico-radiologic features and microbiologic data of patients with SPE in a tertiary care hospital in Busan. METHODS: We retrospectively analyzed clinical and radiologic features of 6 cases with septic pulmonary embolism that occurred from March 2009 to March 2011 in Dong-A university medical center. RESULTS: The mean age of the study population was 58 years, and two men and four women were included. Clinical symptoms included general weakness (5 patients), febrile sensation (4 patients) and pleuritic chest pain (2 patients). Underlying conditions were chemoport infection (4 patients), dental abscess (1 patients), and cellulitis of hip (1 patient). Chest computed tomography revealed bilateral multiple nodular opacities in most patients, and cavitation, central necrosis, feeding vessels were identified. All patients received parenteral antimicrobial therapy with or without central catheter removal, drainage of the extrapulmonary infection. Causative organisms were Pseudomonas aeruginosa (2 patients), Candida albicans (1 patient), Bacillus species (1 patient), and Klebsiella pneumonia (1 patient). CONCLUSIONS: Clinical and radiologic features of septic pulmonary embolism were various and nonspecific. The diagnosis was usually suggested by the presence of a predisposing factor of septic pulmonary embolism and CT findings of bilateral multiple nodular opacities in patients with infectious signs and symptoms. Most important underlying condition was intravascular device infection.
Abscess ; Bacillus ; Candida albicans ; Catheters ; Cellulitis ; Chest Pain ; Drainage ; Female ; Hip ; Humans ; Klebsiella ; Male ; Necrosis ; Pneumonia ; Pseudomonas aeruginosa ; Pulmonary Embolism ; Retrospective Studies ; Sensation ; Sepsis ; Tertiary Healthcare ; Thorax

PURPOSE: The objective of this study was to evaluate skills in handling inhalers and factors associated with these skills among patients with asthma who had undergone treatment at special asthma and allergy clinics in Korea. METHODS: We enrolled 78 subjects who used Turbuhaler and 145 who used Diskus for asthma control at special clinics in 10 university hospitals and visually assessed their skills in handling these inhalers. We also evaluated skills in 137 subjects who had used pressurized metered-dose inhalers (pMDIs) for symptom relief. Age, sex, duration of asthma and inhaler use, smoking status, monthly income, highest grade completed in school and previous instruction for handling inhalers were also measured to evaluate their association with overall inhaler skills. RESULTS: Performance grade was inadequate for 12.8% of participants using Turbuhaler, 6.2% for Diskus, and 23.4% for pMDIs. The success rates for each step in handling the inhalers were relatively high except for the "exhale slowly to residual volume" step, in which success rates ranged from 24.2% to 28.5%. Older age, male sex, lower educational grade, and absence of previous instruction for handling inhalers were associated with inadequate inhaler technique in univariate analysis; however, only older age and absence of previous instruction remained significant independent risk factors in multivariate analysis. CONCLUSIONS: Among Korean asthmatic patients in special asthma and allergy clinics, skills in handling their inhalers were mostly excellent; meanwhile, older age and absence of previous instruction for handling inhalers were associated with inadequate techniques.
Asthma ; Handling (Psychology) ; Hospitals, University ; Humans ; Hypersensitivity ; Male ; Nebulizers and Vaporizers ; Risk Factors ; Smoke ; Smoking

BACKGROUND: Although the prevalence of pulmonary tuberculosis has progressively decreased all over the world, drug-resistant tuberculosis is major obstacle in treating tuberculosis. This study was performed to examine the current prevalence and risk factors of drug resistant tuberculosis in a single tertiary hospital in Busan, Korea. METHODS: We enrolled 367 patients with active pulmonary tuberculosis on a retrospective basis who had undergone mycobacterium culture and drug sensitivity tests between January 2005 and December 2009. We analyzed all clinical and radiographic parameters to find predictors related to drug resistant tuberculosis. RESULTS: At least one incident of drug resistance was found in 75 (20.4%) patients. Isoniazid (18.8%) was the most frequent resistant drug, followed by rifampin (10.9%), ethambutol (7.1%), streptomycin (4.9%), and fluoroquinolone (2.7%). Resistance to second-line drugs was found in 37 (10.1%) patients. Multidrug resistance and extensively drug resistance was evident in 39 (10.6%) and 4 (1.1%) patients, respectively. Using multiple logistic regression analysis, history of previous treatment including relapse (odd ratio [OR], 11.3; 95% confidence interval [CI], 4.92~26.08; p<0.01), treatment failure (OR, 24.1; 95% CI, 5.65~102.79; p<0.01) and an age of below 46 years-old (OR, 3.8; 95% CI, 1.62~8.65; p<0.01) were found to be independent predictors of multidrug resistant tuberculosis. CONCLUSION: We found that the prevalence of drug resistant tuberculosis was considerably high. A careful consideration for possible drug resistant tuberculosis is warranted in patients with a history of previous treatment or for younger patients.
Drug Resistance ; Drug Resistance, Multiple ; Ethambutol ; Humans ; Isoniazid ; Logistic Models ; Mycobacterium ; Prevalence ; Recurrence ; Retrospective Studies ; Rifampin ; Risk Factors ; Streptomycin ; Tertiary Care Centers ; Treatment Failure ; Tuberculosis ; Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary