BACKGROUND: Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a coumarin derivative, has been reported to possess antioxidative, anti-inflammatory and neuroprotective effects. A number of recent observations suggest that the induction of heme oxygenase-1 (HO-1) inhibits inflammation and tumorigenesis. In the present study, we determined the effect of fraxetin on HO-1 expression in HaCaT human keratinocytes and investigated its underlying molecular mechanisms. METHODS: Reverse transcriptase-PCR and Western blot analysis were performed to detect HO-1 mRNA and protein expression, respectively. Cell viability was measured by the MTS test. The induction of intracellular reactive oxygen species (ROS) by fraxetin was evaluated by 2′,7′-dichlorofluorescin diacetate staining. RESULTS: Fraxetin upregulated mRNA and protein expression of HO-1. Incubation with fraxetin induced the localization of nuclear factor-erythroid-2-related factor-2 (Nrf2) in the nucleus and increased the antioxidant response element-reporter gene activity. Fraxetin also induced the phosphorylation of Akt and AMP-activated protein kinase (AMPK)α and diminished the expression of phosphatase and tensin homolog, a negative regulator of Akt. Pharmacological inhibition of Akt and AMPKα abrogated fraxetin-induced expression of HO-1 and nuclear localization of Nrf2. Furthermore, fraxetin generated ROS in a concentration-dependent manner. CONCLUSIONS: Fraxetin induces HO-1 expression through activation of Akt/Nrf2 or AMPKα/Nrf2 pathway in HaCaT cells.
AMP-Activated Protein Kinases* ; Blotting, Western ; Carcinogenesis ; Cell Survival ; Heme Oxygenase-1* ; Heme* ; Humans ; Inflammation ; Keratinocytes ; Neuroprotective Agents ; Phosphorylation ; Reactive Oxygen Species ; RNA, Messenger

The high cardiac output state and an increased incidence of atrial fibrillation are well-known cardiovascular complications of Graves' disease, whereas the valvular complications are less well recognized. With 2D color Doppler echocardiography, the cardiac and valvular function of 39 patients with Graves' disease were evaluated and our data were compared with previous Kage's study. The incidences of mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with Graves' disease were 54% and 51%, respectively. There was no correlation between the incidence of MR and ventricular dilatation. In patients with congestive heart failure (CHF), the incidences of severe TR and atrial fibrillation were significantly higher than in patients without CHF. The incidences of TR and MR in patients with Graves' disease were not different by thyroid function status (hyperthyroid vs. euthyroid). We suggest that the examination for TR and MR in patients with Graves' disease is important not only their high prevalence but also their clinical significance as a risk factor for CHF.
Atrial Fibrillation ; Cardiac Output, High ; Dilatation ; Echocardiography, Doppler, Color ; Graves Disease* ; Heart Failure ; Heart Valve Diseases ; Humans ; Incidence ; Mitral Valve Insufficiency ; Prevalence ; Risk Factors ; Thyroid Gland ; Tricuspid Valve Insufficiency

Ticlopidine is an antiplatelet agent used as a drug to prevent the recurrence of cerebral infarction or ischemic heart disease. Close attention has recently been paid to the superiority of this drug to aspirin in the prevention of stroke. Its mechanism of action differs from aspirin, dipyridamole, and sulfinpyrazone. Inhibition of the adenosine diphosphate induced pathway of platelet aggregation, along with the activation of adenylate cyclase and suppression of platelet-activating factor and thromboxane A2, are the postulated mechanisms of action of ticlopidine. Because ticlopidine causes neutropenia and agranulocytosis in roughly 1% of treated patients, usually within the first 3 months of treatment, this drug has been reserved for patients intolerant to aspirin therapy. We reported two cases of ticlopidine-induced neutropenia and one patient hospitalized with severe neutropenia and pneumonia.
Adenosine Diphosphate ; Adenylyl Cyclases ; Agranulocytosis ; Aspirin ; Cardiovascular Diseases* ; Cerebral Infarction ; Dipyridamole ; Humans ; Myocardial Ischemia ; Neutropenia* ; Platelet Aggregation ; Pneumonia ; Recurrence ; Stroke ; Sulfinpyrazone ; Thromboxane A2 ; Ticlopidine

Ticlopidine is an antiplatelet agent used as a drug to prevent the recurrence of cerebral infarction or ischemic heart disease. Close attention has recently been paid to the superiority of this drug to aspirin in the prevention of stroke. Its mechanism of action differs from aspirin, dipyridamole, and sulfinpyrazone. Inhibition of the adenosine diphosphate induced pathway of platelet aggregation, along with the activation of adenylate cyclase and suppression of platelet-activating factor and thromboxane A2, are the postulated mechanisms of action of ticlopidine. Because ticlopidine causes neutropenia and agranulocytosis in roughly 1% of treated patients, usually within the first 3 months of treatment, this drug has been reserved for patients intolerant to aspirin therapy. We reported two cases of ticlopidine-induced neutropenia and one patient hospitalized with severe neutropenia and pneumonia.
Adenosine Diphosphate ; Adenylyl Cyclases ; Agranulocytosis ; Aspirin ; Cardiovascular Diseases* ; Cerebral Infarction ; Dipyridamole ; Humans ; Myocardial Ischemia ; Neutropenia* ; Platelet Aggregation ; Pneumonia ; Recurrence ; Stroke ; Sulfinpyrazone ; Thromboxane A2 ; Ticlopidine

PURPOSE: Irritable bowel syndrome (IBS) is frequently yet little understood disease. Review was performed to promote understanding on the characteristics, pathophysiology, and risk factors of IBS. CONTENT: IBS is characterized by abdom in women and people with higher educational and social background, but there are some controversies. IBS is diagnosed by the Rome II or Manning criteria after excluding organic gastrointestinal diseases. The pathophysioloy is explained by abnormal control mechanism of central and enteric nervous system. Mucosal immunity, secretions, and neurotransmitter are also associated with the hypersensitivity and motility change of bowel function. Stress is known as a major triggering factor and contributed to symptoms. Other risk factors are genetic elements, childhood experiences, inflammation, anxiety, depression, diet, and sleep disorders.
Anxiety ; Depression ; Diet ; Enteric Nervous System ; Female ; Gastrointestinal Diseases ; Humans ; Hypersensitivity ; Immunity, Mucosal ; Inflammation ; Irritable Bowel Syndrome* ; Neurotransmitter Agents ; Risk Factors* ; Sleep Wake Disorders

Background: The problem with current dental hygienist education is that it operates as an education system based on the national examination rather than on a practical basis; thus, graduates have difficulties in practice after obtaining their license. This study aimed to propose a job-oriented curriculum by analyzing the links between the task analysis of Korean dental hygienists and dental hygiene learning goals. Methods: This study performed a relationship analysis based on a second job analysis study of dental hygienists conducted by the Korea Health Personnel Licensing Examination Institute and the learning goals of the Korean Dental Hygiene Faculty Association. Results: Based on the links between the task and learning goals of the dental hygienist, they were classified into six types: 1) tasks listed in the license exam and learning goal, 2) tasks not listed in the license exam but listed in learning goals, 3) tasks not listed in learning goals, 4) learning goals not related to tasks, 5) learning goals listed in a few tasks, and 6) tasks related to several learning goals. The results showed that most of them correspond to the 5th classification, followed by the 3rd and 4th categories, which are mostly basic science learning goals. Tasks without learning goals are not included in the curriculum; thus, the curriculum needs to be supplemented. The overlapping learning goals of several subjects for one job skill must be reduced in job-oriented education. Conclusion We suggest that the dental hygiene curriculum be developed based on task analysis and reflected in the national dental hygienist exam. The clinical practice performance of dental hygienists will take further leap forward through task-oriented education.

The numb chin syndrome (NCS) is characterized by chin or lower lip numbness restricted to the distribution of mental nerve (the distal trigeminal nerve). This uncommon neuropathy may be associated with neoplastic disease and usually appeared as a late manifestation of systemic malignancy, and it is an important sign for early diagnosis and prediction of clinical course and prognosis of hematologic malignancy. The numb chin syndrome is usually associated with a poor prognosis although various therapeutic strategies led to resolution of this syndrome. We report 2 cases of numb chin syndrome ; one in acute leukemia in early course of disease before diagnosis of leukemia and the other in leptomeningeal seeding of malignant lymphoma. The therapeutic response and prognosis were poor, a patient of malignant lymphoma expired in two months and a patient of acute leukemia is alive at present but the disease was relapsed in 5 months after complete remission.
Chin* ; Diagnosis ; Early Diagnosis ; Hematologic Neoplasms ; Humans ; Hypesthesia ; Leukemia ; Lip ; Lymphoma ; Prognosis

OBJECTIVES: The conventional methods such as smear or culture of Mycobacteria have been proved either low sensitivity and specificity or time-consuming. Polymerase chain reaction (PCR) is a rapid and sensitive alternative method to diagnose mycobacterial infection. We investigated the positive rate of sputum PCR for Mycobacterium tuberculosis by consecutive tests for its application in clinical practice. METHODS: Sputum AFB smear, culture and serial AFB PCR test were performed in all patients who were suspected of pulmonary tuberculosis. Among them, 128 patients with positive sputum PCR test were enrolled from January 1996 through March 1997. The diagnostic criteria of pulmonary tuberculosis were sputum AFB smear positive, culture positive or pathologically proven granuloma. TB-CR TM kit (Bioneer, seoul, Korea), which amplifies insertion sequence (IS6110) of Mycobacterium tuberculosis complex, was used for sputum AFB PCR. RESULTS: Of 128 patients, active pulmonary tuberculosis were 107 (male:74, female:33, mean age:48.9 year). Cumulative positive rate of sputum AFB PCR test was 89% at 1st test, 95% at 2nd test, 98% at 3rd test and 100% at 4th test. The sensitivity of sputum PCR, smear and culture was 98.0% (105/107), 85.0% (91/107) and 82.8% (77/107), respectively. The positive predictive value of sputum PCR was 83.6% (107/128). There were 21 patients who showed positive PCR test did not meet the diagnostic criteria of active tuberculosis. They had old tuberculosis with destroyed lung, history of anti- tuberculous medication (9/21), extrapulmonary tuberculosis (6/21) and other diseases (6/21). CONCLUSION: Sputum PCR test is a sensitive diagnostic tool in early diagnosis of pulmonary tuberculosis when it has been performed serially, we recommend at least 2 consecutive PCR test to achieve the sensitivity of 95%.
Early Diagnosis ; Granuloma ; Humans ; Lung ; Mycobacterium tuberculosis ; Polymerase Chain Reaction* ; Sensitivity and Specificity ; Seoul ; Sputum* ; Tuberculosis ; Tuberculosis, Pulmonary*

BACKGROUND: Muscle cramps in cirrhotic patients are not serious symptoms but have frequently bad effect on their quality of life. We have evaluated the effectiveness of treatment with eperisone hydrochloride, an antispastic agent, on muscle cramps in cirrhotic patients. METHODS: Sixty five cirrhotic patients (cramps 35, no cramps 30) were included in our study. Thirty five patients with muscle cramps were questioned about the frequency and localization of muscle cramps. All patients were evaluated a physical findings and blood chemistry at the beginning of the study and after one month. Eperisone hydrochloride 50 mg per day were given orally to the patients with muscle cramps. RESULTS: There were significant differences for the number of diuretics use (p=0.019), hemoglobin (p=0.005), platelet (p=0.007), total bilirubin (p=0.003), albumin (p=0.000), total calcium (p=0.0001) and Na+ (p=0.001) between with and without muscle cramps. Muscle cramps were found to occur in calf muscles (60%) and hands (54%), to occur several times a week (76%), mainly during sleep (73%) and to last for several minutes (53%). After a month, muscle cramps completely disappeared in 7 patients (20%), decreased in frequency in 18 patients (51%) and were unaltered in 10 patients (29%). Side effects were observed in 7 patients (epigastric discomfort in five, fatigue in two) but any patients were not stopped. CONCLUSIONS: Eperisone hydrochloride was significantly effective in treatment for the muscle cramps of the patients with liver cirrhosis. In addition, this agents was well tolerated without any serious adverse effects in the majority of the patients.
Bilirubin ; Blood Platelets ; Calcium ; Chemistry ; Diuretics ; Fatigue ; Hand ; Humans ; Liver Cirrhosis* ; Liver* ; Muscle Cramp* ; Muscles ; Quality of Life