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BACKGROUND: To investigate the role of alpha-adrenergic receptors in the development of delayed afterdepolarization, the effect of alpha-adrenoceptor stimulation and blockade on ouabain induced delayed afterdepolarization(DDAD) was examined in rabbit heart Purkinje fibers. METHODS: Purkinje fibers, taken from adult rabbit(1.8 - 2.0kg) heart anesthetized with penobarbital, were mounted in a Luicite chamber and superfused with Tyrode's solution. The transmembrane potentials were measured by the conventional microelectrode technique while the fibers were being stimulated with rectangular pulses of 50% above threshold voltage. The delayed afterdepolarizations were induced by overdrive excitation in the presence of ouabain. RESULTS: Delayed afterdepolarizations were not observed during superfusion of the control Tyrode's solution containing propranolol(5x10(-7)M). However, the addition of ouabain in the presence of propranolol elicited DADs which were dose-, time- and drive cycle length- dependent. Phenylephrine(PE ; 10(-7)M), and alpha-adrenoceptor agonist, potentiated the ouabain-induced DAD during the initial superfusion(for 10 or 20 min) of the test Tyrode's solution. However, it was followed by attenuating-effects after a superfusion time of 50 to 60 min. Both effects showed ouabain dose-dependence. Ouabain(2x10(-7)M), in the presence of propranolol, depolarized the maximum diastolic potential and shortened the action potential duration, and the addition of PE(10(-7)M) did not affect the characteristics of action potential except a decrease in velocity of phase 0 depolarization. Prazosin, an alpha1-adrenoceptor antagonist, inhibited the PE's enhancing effects of ouabaininduced DDAD at 20 min superfusion, but did not affect the attenuating-effects of PE at 60 min superfusion. On the other hand, yohimbine, an alpha2-adrenoceptor antagonist, did not affect the PE's DAD potentiating-effects at 20 min superfusion, but inhibited the attenunating-effects of PE at 60 min superfusion. CONCLUSION: It is inferred that alpha-adrenergic stimulation induce delayed afterdepolarization and triggered activity in the rabbits, being responsible for the arrhythmia development, and the effects are mainly due to the action of alpha1-subtpe adrenoceptor stimulation.
Action Potentials ; Adult ; Arrhythmias, Cardiac ; Hand ; Heart ; Humans ; Membrane Potentials ; Microelectrodes ; Ouabain ; Prazosin ; Propranolol ; Purkinje Fibers ; Rabbits ; Receptors, Adrenergic, alpha* ; Yohimbine

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the “fit for purpose” application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in C(max) of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.
Area Under Curve ; Caffeine* ; Ciprofloxacin* ; Computer Simulation ; Drug Discovery ; Humans ; In Vitro Techniques ; Permeability ; Pharmacokinetics* ; Solubility ; Tissue Distribution

BACKGROUND: Doxylamine is an over-the-counter drug that is popular in the treatment of insomnia. Doxylamine is relatively safe but can cause rhabdomyolysis. The aim of this study was to evaluate whether the incidence of rhabomyolysis increased in elderly patients (age> or =65 years) with doxylamine overdose. METHODS: This study included 108 patients admitted to an Emergency Department after doxylamine overdose between January 1, 2000, and March 31, 2013. Age, sex, time ingested before admission, amount of drug ingested, gastric lavage, tachycardia, vomiting, hematuria, blood urea nitrogen, blood creatinine, urine pH, and alcohol ingestion were investigated for the risk factors of rhabdomyolysis. RESULTS: Forty-three patients (47.6%) developed rhabdomyolysis. Of 16 elderly patients, 11 developed rhabdomyolysis. Of the 92 patients <65 years-of-age, 34 developed rhabdomyolysis. Advanced age, alcohol ingestion, and increased blood creatinine level were significantly associated with the development of rhabdomyolysis. CONCLUSION: In elderly patients with doxylamine overdose, the incidence rate of rhabdomyolysis may be increased. A high index of suspicion and evaluation of rhabdomyolysis is warranted in elderly patients with doxylamine overdose.
Aged* ; Blood Urea Nitrogen ; Creatinine ; Doxylamine* ; Eating ; Emergencies ; Gastric Lavage ; Hematuria ; Humans ; Hydrogen-Ion Concentration ; Incidence* ; Rhabdomyolysis* ; Risk Factors ; Sleep Initiation and Maintenance Disorders ; Tachycardia ; Vomiting

Oral and maxillofacial infection is the oldest and most common disease in human history. The infection ranges from the low-grade infection that only requires minimal treatment to the high-grade and life-threatening fascial space infection. In this study, the data on oral and maxillofacial infections were analyzed to aid in the diagnosis and treatment, and to predict the prognosis. This report was based on data from 831 patients with oral and maxillofacial infection (394 males and 437 females) who were hospitalized in the Department of Oral and Maxillofacial surgery of Chosun University Dental Hospital from January 1998 to May 2005. The ratio of males to females was 0.9:1. By age, patients between 60 and 70 years old were the greatest in number (17.1%), while only 5.9% of the patients were between 10 and 20 years old. The most common cause of infection was odontogenic origin (84.4%), followed by post-extraction infection (6.2%), unknown (5.9%), and trauma (3.5%). The most common fascial space involved was the buccal space (39.4%), followed by the canine (20.6%), submandibular (15.9%), pterygomandibular (9.5%), submental (7.6%) and sublingual (2.8%) space. The number of the involved fascial space was one (75.2%), two (19.8%), or more than three (5.0%). In terms of the treatment duration, the hospitalization period of 6 to 10 days was the greatest in number (49.9%). All patients had uneventful recovery without major complication. There are statistically significant correlations between age and treatment period, and the involved space and treatment period, but no correlations between the variables of sex and treatment.
Diagnosis ; Female ; Hospitalization ; Humans ; Male ; Prognosis ; Surgery, Oral

OBJECTIVES: Recently, comparison of drug responses on gene expression has been a major approach to identifying the functional similarity of drugs. Previous studies have mostly focused on a single feature, the expression differences of individual genes. We provide a more robust and accurate method to compare the functional similarity of drugs by diversifying the features of comparison in gene expression and considering the sample dependent variations. METHODS: For differentially expressed gene measurement, we modified the conventional t-test to normalize variations in diverse experimental conditions of individual samples. To extract significant differentially co-expressed gene modules, we searched maximal cliques among the co-expressed gene network. Finally, we calculated a combined similarity score by averaging the two scaled scores from the above two measurements. RESULTS: This method shows significant performance improvement in comparison to other approaches in the test with Connectivity Map data. In the test to find the drugs based on their own expression profiles with leave-one-out cross validation, the proposed method showed an area under the curve (AUC) score of 0.99, which is much higher than scores obtained with previous methods, ranging from 0.71 to 0.93. In the drug networks, we could find well clustered drugs having the same target proteins and novel relations among drugs implying the possibility of drug repurposing. CONCLUSIONS: Inclusion of the features of a co-expressed module provides more implications to infer drug action. We propose that this method be used to find collaborative cellular mechanisms associated with drug action and to simply identify drugs having similar responses.
Biomarkers, Pharmacological ; Drug Repositioning ; Gene Expression Regulation ; Gene Expression* ; Gene Regulatory Networks ; Methods ; Transcriptome*

Pigmented contact dermatitis denotes a kind of secondary hyperpigmentation resulting from recurrent contact dermatitis of low degree. Cinnamic aldehyde is a component of cinnamon,which is widely used in foods and fragrances. A 21 year-old girl presented with a well-defined dark brownish patch on right side of chest for 4 years. Histopathologic examination revealed epidermal spongiosis, hypermelanosis of basal layer, scattered melanophages and mild perivascular inflammatory cell infiltration in the upper dermis Patch test findings were positive to fragrance mix, cinnamic aldehyde and body shampoo which was used by the patient. Peroral challenge with cinnamon tea resulted in flare-up of the positive patch-test sites and the skin lesion.
Aldehydes* ; Cinnamomum zeylanicum ; Dermatitis, Contact* ; Dermis ; Female ; Humans ; Hyperpigmentation ; Patch Tests ; Skin ; Tea ; Thorax ; Young Adult

Background: Job training influences the overall working environment and worker's well-being. The purpose of this study is to find the relationship between job training and subjective well-being in accordance with occupations and understand the influence of task characteristics—work creativity and task variety (WCTV)—on the effect of training. Methods: A cross-sectional study based on the Fifth Korean Working Conditions Survey was conducted on 50,205 workers in the Republic of Korea. The World Health Oorganization–5 well-being index was used to measure their subjective well-being. The relationship between job training and subjective well-being was divided in accordance with the level of WCTV. Results: Training paid for by employer showed a negative effect on subjective well-being when received for more than 3 days (OR 0.88, p<0.01) in the last 12 months. Training paid for by oneself showed a positive linkage with well-being when the level of training was 1–3 days (Odds ratio = 1.55, p<0.001). This result showed different aspects in accordance with the level of WCTV. For the high WCTV group, the aforementioned results were reaffirmed, but for the group with low WCTV, job training did not show a statistically significant result on well-being. On-the-job training was not related to subjective well-being regardless of the level of WCTV. Conclusion Job training had different effects on subjective well-being depending on the type and frequency of training, as well as the WCTV. It is imperative to comprehensively apply different types of job training in accordance with the characteristics of occupations to uplift workers' well-being.

Background: Job training influences the overall working environment and worker's well-being. The purpose of this study is to find the relationship between job training and subjective well-being in accordance with occupations and understand the influence of task characteristics—work creativity and task variety (WCTV)—on the effect of training. Methods: A cross-sectional study based on the Fifth Korean Working Conditions Survey was conducted on 50,205 workers in the Republic of Korea. The World Health Oorganization–5 well-being index was used to measure their subjective well-being. The relationship between job training and subjective well-being was divided in accordance with the level of WCTV. Results: Training paid for by employer showed a negative effect on subjective well-being when received for more than 3 days (OR 0.88, p<0.01) in the last 12 months. Training paid for by oneself showed a positive linkage with well-being when the level of training was 1–3 days (Odds ratio = 1.55, p<0.001). This result showed different aspects in accordance with the level of WCTV. For the high WCTV group, the aforementioned results were reaffirmed, but for the group with low WCTV, job training did not show a statistically significant result on well-being. On-the-job training was not related to subjective well-being regardless of the level of WCTV. Conclusion Job training had different effects on subjective well-being depending on the type and frequency of training, as well as the WCTV. It is imperative to comprehensively apply different types of job training in accordance with the characteristics of occupations to uplift workers' well-being.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia particularly in the elderly and a potent risk factor for ischemic stroke. Screening for AF in asymptomatic individuals might prevent strokes by earlier detection and anticoagulation therapy. We investigated the prevalence of AF in the Korean elderly and its clinical characteristics. METHODS: This study included 1,483 participants (839 males, 644 females) ≥60 years (72.9±5.4 years) who had undergone electrocardiogram (ECG) screening at the senior health promotion center, Gwangju, from March 2014 to June 2014. Their assessments included 12 lead electrocardiograms, questionnaires and physical examinations. RESULTS: AF was detected in 46 individuals (3.1%), and newly detected in 20 of these 46 (43.4%). The prevalence of AF increased sharply with age-1.0% in 60-69 years group, 3.3% in 70-79 years group, and 7.2% in ≥80 years group. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.05-1.17; p<0.001), male gender (OR 5.28, 95% CI 2.04-13.66; p=0.001), obesity (body mass index>25kg/m2) (OR, 2.17; 95% CI, 1.14-4.11; p=0.017), and heart failure (OR, 8.74; 95% CI, 1.45-52.46, p=0.018) were associated with increased risk for AF. CONCLUSION: The prevalence of AF in the Korean elderly was 3.1% and increased steeply with age from 1.0% to 7.2%. Screening with ECG may be considered as nearly half (43.4%) of AF cases were newly detected.
Aged* ; Arrhythmias, Cardiac ; Atrial Fibrillation* ; Electrocardiography ; Epidemiology ; Gwangju ; Health Promotion ; Heart Failure ; Humans ; Korea* ; Logistic Models ; Male ; Mass Screening ; Obesity ; Physical Examination ; Prevalence* ; Risk Factors ; Stroke