The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

BACKGROUND: There were a few studies which were conducted to know about the behavior of the chronic obstructive pulmonary diseases (COPD) patients. The aims of this study was to explore the behaviour of COPD patients, such as awareness and impact of disease, the pathway of visiting doctors, and the treatment pattern and preference. METHODS: A face-to-face interview of 300 subjects with COPD was conducted. RESULTS: The most concerned symptom which made the respondents to visit the hospital was 'breathlessness' (78%). Only 58% of them knew the exact diagnosis. Seventy-three percent of them visited the hospital 'once a month' or 'once every 2 month'. They have made 12.8 prescheduled visits to the hospital in the past 1 year. Unscheduled visits and hospital stay figured to two in the past year. Only 11% of respondents felt they were currently in good health. 'Severe' and 'very severe' COPD patients perceived their health to be in a worse condition than 'mild' and 'moderate' COPD patients. When conditions worsened, 42% of patients were hospitalized. The most common prescription treatment was a fixed combination of inhaled corticosteroids and long-acting beta2 agonists (48%), followed by a long acting anticholinergics (38%). CONCLUSION: Over forty percent of the patients didn't know exactly about their condition. Most of them had a negative attitude toward their current health status. Doctors need to know more about COPD patients in terms of their attitude toward the disease, impact of the disease, interaction with healthcare professionals and treatment related problems.
Adrenal Cortex Hormones ; Cholinergic Antagonists ; Surveys and Questionnaires ; Delivery of Health Care ; Humans ; Length of Stay ; Lung Diseases, Obstructive ; Prescriptions ; Pulmonary Disease, Chronic Obstructive

BACKGROUND/AIMS: ERCP is being used increasingly as a diagnostic and therapeutic tool for children with pancreaticobiliary disorders. Differences between thirteen pediatric ERCPs and adult ERCPs were reviewed with respect to their indications, method of anesthesia, choice of endoscope and complications. METHODS: The medical records of 13 ERCPs for 10 children (age: 23 months to 14 years) done between 2005 and 2008 were reviewed retrospectively. RESULTS: ERCP was indicated for gallstone pancreatitis (6), choledocholithiasis (3), and unexplained pain (1). The method of anesthesia was intravenous sedation with a single agent or a combination of midazolam, propofol or ketamine. The quality of sedation was satisfactory in 10 cases and unsatisfactory in three cases. These 3 cases were less than 8 years old and sedated with a combination of midazolam and propofol. Selective biliary cannulation was successful in 92.3% (12/13) of attempts. Therapeutic ERCP included sphincterotomy (4), endoscopic papillary balloon dilatation (3), and both (5). Complications occurred in 7.7% of attempts (1/13; 1 duodenal perforation) which was successfully managed by surgery. CONCLUSIONS: Pediatric ERCP is a feasible and useful technique. Special caution is needed, however, because of differences with adult ERCP in terms of the effectiveness of intravenous sedation, complications, and size of the gastrointestinal tract.
Adult ; Anesthesia ; Catheterization ; Child ; Cholangiopancreatography, Endoscopic Retrograde ; Choledocholithiasis ; Dilatation ; Endoscopes ; Gallstones ; Gastrointestinal Tract ; Humans ; Ketamine ; Medical Records ; Midazolam ; Pancreatitis ; Propofol ; Retrospective Studies

BACKGROUND: LB20304(gemifloxacin) is a new fluoroquinolone antibacterial agent with excellent activity against both Gram-negative and Gram-positive organisms. In vitro studies using clinical isolates have shown gemifloxacin to be highly active against penicillin-resistant strains of S. pneumoniae and in contrast to other reference quinolones, gemifloxacin retained good activity against clinical isolates of S. pneumoniae that were resistant to other members of the quinolone class. Therefore, gemifloxacin is thought to be effective in treating acute bacterial exacerbation of chronic bronchitis(AECB). The objective of this study was to evaluate the efficacy and safety of oral gemifloxacin at doses of 160mg or 320mg once daily for 7 days for the treatment of AECB in Korean adult population. METHODS: This was a randomized, multicenter, double-blind, parallel group Phase II study to assess the clinical and antibacterial efficacy and safety of oral gemifloxacin for the treatment of AECB. Treatment Group A (67 patients) took oral gemifloxacin 160mg once daily for seven days and treatment Group B (70 patients) took oral gemifloxacin 320mg once daily for seven days. RESULTS: The demographic profiles of the two treatment groups were similar. The clinical response at follow-up was 84.2% in the gemifloxacin 160-mg group, and 88.7% in the gemifloxacin-320 mg group, showing no statistically significant difference between two treatment groups(p=0.49). The clinical response at the end of therapy was 96.5% in the 160-mg group, and 96.4% in the 320-mg group. The bacteriological response at the end of therapy and follow-up were 81.8% and 78.9%, respectively, in the 160-mg group, and 86.4% and 84.2%, respectively, in the 320-mg group, showing no statistically significant difference between two treatment groups(p=0.68 and 0.68, respectively). S. pneumoniae(12 isolates) and H. influenzae(10 isolates) were the most prevalent pathogens. The MICs were lower for gemifloxacin than other quinolones against these key pathogens, and for S. pneumoniae, the MICs for gemifloxacin were considerably lower(< or = 0.03 ug/mL) than those for other quinolones, beta-lactams and acrolides. In the period on-therapy plus 30 days post-therapy, a total of 18 patients(26.9%) in the gemifloxacin 160mg group and 22 patients(31.4%) in the 320mg group reported at least one adverse event(AE). The most frequently reported AE was abdominal pain(3/67 patients, 4.5%) in the gemifloxacin 160mg group and increased level of hepatic enzyme(5/70 patients, 7.1%) in the 320mg group. The overall AE profiles for the two treatment groups were similar. Two out of 67 patients(3.0%) in the gemifloxacin 160mg group and 1/70 patients(1.4%) in the 320mg group reported at least one serious AE, however, none of which was considered by the investigator to be of suspected or probable relationship to study medication. CONCLUSION: The results of this study showed that gemifloxacin at doses of 160mg or 320mg once daily for 7 days in the treatment of acute exacerbations of chronic bronchitis(AECB) in adult Koreans was a very effective and safe treatment both clinically and bacteriologically.
Adult* ; beta-Lactams ; Bronchitis, Chronic* ; Double-Blind Method* ; Follow-Up Studies ; Humans ; Mesylates* ; Pneumonia ; Quinolones ; Research Personnel

Atlantoaxial subluxation causing spinal cord compression at the craniovertebral junction may develop in patients with rheumatoid or psoriatic arthritis. There have been only a few reports of atlantoaxial subluxation in patients with psoriatic arthritis in the world. The authors report a case of psoriatic arthritis with atlantoaxial subluxation accompaning periodontoid pannus formation. This 53-year-old man with a 3-year history of psoriatic skin lesion presented with nuchal pain and myelopathy. We performed decompression by C1 total laminectomy with transarticular screw fixation and obtained remarkable improvement in motor function and immediate postoperative stability.
Arthritis, Psoriatic* ; Decompression ; Humans ; Laminectomy ; Middle Aged ; Skin ; Spinal Cord Compression ; Spinal Cord Diseases

BACKGROUND: Exercise testing is a standard noninvasive method used in the evaluation and management of patients with suspected coronary artery disease. However, patients with lower limb impairment are unable to undergo a standard bicycle or treadmill test. Alternative methods of exercise testing are needed for patients with vascular, orthopedic or neurologic conditions who cannot perform leg exercise. This study was aimed to determine the diagnostic accuracy of arm exercise thallium-201 SPECT for evaluating chest pain in patients unable to perform leg exercise. METHOD: Twenty-five anginal patients performed arm ergometry testing in conjunction with thallium-201 SPECT. Thereafter all underwent coronary angiography. RESULT: Significant coronary artery disease (> or =50% stenosis) in at least one vessel was present in 22 (88%) of the 25 patients. The sensitivity of thallium-201 SPECT for detecting coronary artery disease was 91%, which was significantly higher than the 32% sensitivity found with the electrocardiographic response alone (p <0.001). Thallium-201 SPECT yielded a sensitivity of 88, 86 and 100% for one, two, and three vessel diseases, respectively, and an 84% sensitivity and 81% specificity for detecting individual vessel stenosis. CONCLUSION: Arm exercise thallium-201 SPECT is useful for detecting coronary artery disease in patients unable to perform leg exercise. In addition, it provides an information regarding exercise tolerance. Therefore, this test appears to be reliable and useful and should be considered in the detection of coronary artery disease in nonambulatory patients.
Angina Pectoris ; Arm* ; Chest Pain ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Vessels* ; Electrocardiography ; Exercise Test ; Exercise Tolerance ; Humans ; Leg ; Lower Extremity ; Orthopedics ; Sensitivity and Specificity ; Tomography, Emission-Computed, Single-Photon*

BACKGROUND: Rifampicin(RFP) is a key component of the antituberculous short-course chemotherapy and the RFP resistance is a marker of multi-drug resistant(MDR) tuberculosis. RpoB gene encodes the beta-subunit of RNA polymerase of M. tuberculosis which is the target of RFP. And rpoB gene mutations are the cause of RFP resistance of M. tuberculosis. Although several reports showed that PCR-SSCP would be a rapid diagnostic method for identifying the REP resistance, there were few reports performed using direct, dinical specimens. So we performed PCR-SSCP analysis of rpoB gene of M. tuberculosis in direct, clinical specimens. METHODS: 75 clinical specimens were collected from patients at Asan Medical Center from June to August 1996. After PCR of IS 6110 fragments, 43 both AFB smear-positive and IS 6110 fragment PCR-positive specimens were evaluated. The RFP susceptibility test was referred to the referral laboratory of the Korean Tuberculosis Institute. DNA was extracted by bead beater method. And heminested PCR was done using 0.1ul(1uCi) [alpha-32P]-dCTP. SSCP analysis was done using non-denaturating MDE gel electrophoresis. RESULTS: The results of PCR of IS 6110 fragments of M. tuberculosis were positive in 55(73%) cases of 75 AFB smear-positive clinical specimens. Of the 55 specimens, RFP susceptibility was confirmed in only 43 specimens. Of the 43 AFB smear-positive and IS6110 fragment-positive specimens, 29 were RFP susceptible and 14 were RFP resistant. All the RFP susceptible 29 strains showed the same mobility compared with that of RFP sensitive H37Rv in SSCP analysis of ropB gene. And all the other RFP resistant 13 strains showed the different mobility. In other words they showed 100% identical results between PCR-SSCP analysis and traditional susceptibility test. CONCLUISON: The PCR-SSCP analysis of rpoB gene in direct clinical specimens could be used as a rapid diagnostic method for detecting RFP resistant M. tuberculosis.
Chungcheongnam-do ; DNA ; DNA-Directed RNA Polymerases ; Drug Resistance, Multiple ; Drug Therapy ; Electrophoresis ; Humans ; Mycobacterium ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Referral and Consultation ; Rifampin* ; Tuberculosis*

We report a case of a 20-year-old woman who presented with fever, dry cough and pulmonary consolidation at the left upper lobe on chest radiograph. Fiberoptic bronchoscopy revealed obstruction of the left upper lobar bronchus with exophytic mass and multiple nodular protruding lesions at the left main bronchus. Endobronchial actinomycosis was confirmed by demonstration of sulfur granule through the bronchoscopic biopsy of nodular lesion. Intravenous administration of penicillin G followed by oral tetracycline therapy for 5 months resulted in complete recovery of symptoms which had been present for 3 months prior to therapy. Infiltrative consolidation on the chest X-ray disappeared and all the lesions shown by bronchoscopy were nearly normalized after 6 months only to remain small nodular remnants at the left main bronchus. Endobronchial actinomycosis should be included in the differential diagnosis of endobronchial mass.
Actinomycosis* ; Administration, Intravenous ; Biopsy ; Bronchi ; Bronchoscopy ; Cough ; Diagnosis, Differential ; Female ; Fever ; Humans ; Penicillin G ; Radiography, Thoracic ; Sulfur ; Tetracycline ; Thorax ; Young Adult

Protective effect of human cerebrospinal fluid antioxidants against enzyme inactivation caused by metal-catalyzed oxidation systems were investigated. When purified glutamine synthetase(GS) was incubated with human cerebrospinal fluid(CSF), the enzyme was progressively inactivated. Catalase and EDTA could inhibit the enzyme inactivation by 50-80%. Small-molecular(Mr<-10,000) fraction of CSF inactivated the exogenous GS, but large-molecular(Mr>-10,000) fraction did not. The GS inactivation by the small-molecular fraction was also markedly inhibited by catalase and EDTA. These results suggested that metal-catalyzed oxidation is involved in the GS inactivation by the small-molecular fraction of CSF. Dithiothreitol(DTT)was shown to inhibit almost completely the oxidative inactivation of GS by CSF. However, DTT inhibited only partially the oxidative inactivation of GS caused by small-molecular fraction of CSF. When large-molecular fraction of CSF was separated by anion-exchange HPLC chromatography, there was a peak of antioxidant activity inhibiting the small-molecular fraction-induced GS inactivation in the presence of DTT. The antioxidant activity was neutralized by monoclonal antibodies to transthyretin. Purified transthyretin was found to efficiently inhibit ascorbate/Cu2+-induced GS inactivation in the presence of DTT. Uric acid and glucose did not shoe any protective effect on the GS inactivation in the same condition. The above results suggest that metal-catalyzed oxidation occurs normally in human CSF, and the transthyretin may play an important role as a CSF antioxidant in protecting proteins from metal-catalyzed oxidation.
Antibodies, Monoclonal ; Antioxidants ; Catalase ; Cerebrospinal Fluid* ; Chromatography ; Chromatography, High Pressure Liquid ; Edetic Acid ; Glucose ; Glutamine ; Humans* ; Prealbumin* ; Shoes ; Uric Acid

Neurotoxicity in the workplace may occur with exposure to scores of chemicals. Although large acute outbreaks of the occupational neurological disease are rare, the incidence of occupational neurotoxicity in its subtler aspects is unknown. A working knowledge of both the major occupational neurotoxic solvents and the tools used by clinical neurologists and neurotoxicologists to evaluate neurotoxicity in working population is a necessity for the occupational physician. To investigate the effects of carbon disulfide(CS2) on the peripheral nerve system using the nervous conduction study, 105 male workers working in the spinning room of a viscose rayon factory were examined and compared with a sex and age matched, unexposed 105 male controls using t-test analysis. 72.4% of CS2-exposed workers complained of neurological symptoms, and the abnormal cases in nerve conduction study were 48.6%. The abnormal cases of nerve conduction study increased in number according as the age and duration of exposure increased. In this study, asymptomatic workers were confirmed to have subclinical neuropathy by nerve conduction study. Also as there were abnormal cases even in its duration of exposure below 4 years, nerve conduction study turned out to be ways of discovering of early peripheral neuropathy. In nerve conduction study, the amplitude, velocity, F-wave latency and H-reflex of the motor and sensory nerves in both upper and lower extremities were significant different between CS2-exposed workers and the controls. From the pathological viewpoint, both segmental and axonal degenerations were assumed in this study.
Axons ; Carbon Disulfide* ; Carbon* ; Disease Outbreaks ; H-Reflex ; Humans ; Incidence ; Lower Extremity ; Male ; Neural Conduction ; Peripheral Nerves ; Peripheral Nervous System Diseases* ; Solvents