Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H₂O₂-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.
Acetylcysteine ; Bilirubin ; Carbon Monoxide* ; Carbon* ; Down-Regulation* ; Endothelial Cells ; Heme ; Humans ; Iron ; RNA, Messenger ; RNA, Small Interfering ; Vascular Diseases

A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic ; Acetabulum ; Adult ; Decompression ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Foraminotomy* ; Humans ; Neurologic Manifestations ; Radiculopathy ; Sacrum ; Toes ; Wounds and Injuries

A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic ; Acetabulum ; Adult ; Decompression ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Foraminotomy* ; Humans ; Neurologic Manifestations ; Radiculopathy ; Sacrum ; Toes ; Wounds and Injuries

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an important role in vascular functions, including vasorelaxation. We here investigated the pharmacological effect of the natural product syringaresinol on vascular relaxation and eNOS-mediated NO production as well as its underlying biochemical mechanism in endothelial cells. Treatment of aortic rings from wild type, but not eNOS-/- mice, with syringaresinol induced endothelium-dependent relaxation, which was abolished by addition of the NOS inhibitor NG-monomethyl-L-arginine. Treatment of human endothelial cells and mouse aortic rings with syringaresinol increased NO production, which was correlated with eNOS phosphorylation via the activation of Akt and AMP kinase (AMPK) as well as elevation of intracellular Ca2+ levels. A phospholipase C (PLC) inhibitor blocked the increases in intracellular Ca2+ levels, AMPK-dependent eNOS phosphorylation, and NO production, but not Akt activation, in syringaresinol-treated endothelial cells. Syringaresinol-induced AMPK activation was inhibited by co-treatment with PLC inhibitor, Ca2+ chelator, calmodulin antagonist, and CaMKKbeta siRNA. This compound also increased eNOS dimerization, which was inhibited by a PLC inhibitor and a Ca2+-chelator. The chemicals that inhibit eNOS phosphorylation and dimerization attenuated vasorelaxation and cGMP production. These results suggest that syringaresinol induces vasorelaxation by enhancing NO production in endothelial cells via two distinct mechanisms, phosphatidylinositol 3-kinase/Akt- and PLC/Ca2+/CaMKKbeta-dependent eNOS phosphorylation and Ca2+-dependent eNOS dimerization.
Animals ; Aorta/*drug effects/physiology ; Enzyme Activation/drug effects ; Furans/*pharmacology ; Gene Deletion ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Humans ; Lignans/*pharmacology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/genetics/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide Phospholipase C/metabolism ; Phosphorylation/drug effects ; Protein Multimerization/*drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Vasodilation/*drug effects

This study was designed to investigate the effects of the prenylated flavonoid kurarinone on TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis and its underlying mechanism. A low dose of kurarinone had no significant effect on apoptosis, but this compound markedly promoted tumor cell death through elevation of Bid cleavage, cytochrome c release and caspase activation in HeLa cells treated with TRAIL. Caspase inhibitors inhibited kurarinone-mediated cell death, which indicates that the cytotoxic effect of this compound is mediated by caspase-dependent apoptosis. The cytotoxic effect of kurarinone was not associated with expression levels of Bcl-2 and IAP family proteins, such as Bcl-2, Bcl-xL, Bid, Bad, Bax, XIAP, cIAP-1 and cIAP-2. In addition, this compound did not regulate the death-inducing receptors DR4 and DR5. On the other hand, kurarinone significantly inhibited TRAIL-induced IKK activation, IkappaB degradation and nuclear translocation of NF-kappaB, as well as effectively suppressed cellular FLICE-inhibitory protein long form (cFLIPL) expression. The synergistic effects of kurarinone on TRAIL-induced apoptosis were mimicked when kurarinone was replaced by the NF-kappaB inhibitor withaferin A or following siRNA-mediated knockdown of cFLIPL. Moreover, cFLIP overexpression effectively antagonized kurarinone-mediated TRAIL sensitization. These data suggest that kurarinone sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-kappaB-dependent cFLIP expression, indicating that this compound can be used as an anti-tumor agent in combination with TRAIL.
Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; CASP8 and FADD-Like Apoptosis Regulating Protein/*genetics/metabolism ; Caspase 3/metabolism ; Caspase 8/metabolism ; Drug Synergism ; Enzyme Activation/drug effects ; Flavonoids/*pharmacology ; Gene Expression/drug effects ; Gene Knockdown Techniques ; HeLa Cells ; Humans ; NF-kappa B/antagonists & inhibitors/*metabolism ; Protein Transport/drug effects ; RNA, Small Interfering/genetics ; Signal Transduction ; TNF-Related Apoptosis-Inducing Ligand/*physiology ; Up-Regulation/drug effects

PURPOSE: Walnut (WN) allergy in young children has rarely been reported in Asia. This study focused on the clinical characteristics of WN allergy, co-sensitization, and cross-reactivity between WN and peanut (PN) in young Korean children. METHODS: This study was based on a data analysis of 22 patients, all under the age of 4 years, who were diagnosed with allergic disease at Ajou University Hospital from January 2009 to December 2010. They were suspected to have a WN allergy or needed a screening examination to exclude food allergy. Sera from all children were analyzed for PN-, WN-, and pine nut-specific immunoglobulin E (IgE) (ImmunoCAP). Clinical details, feeding, and familial history of patients were collected by medical history. Additionally, we produced WN, PN, and pine nut extracts, and sera were tested with an enzyme linked immunosorbentassay inhibition test. RESULTS: The subjects were 16 male and 6 female with a median aged of 24 months. Ten of 22 had a definite history of WN exposure. Among them, two (4.28 kU/L, 11.1 kU/L) were diagnosed with anaphylaxis, four (7.34 to 27.4 kU/L) were diagnosed with angioedema, and four (1.35 to 3.17 kU/L) were diagnosed with urticaria. We confirmed that PN in the IgE-ELISA was profoundly inhibited by the WN extract. CONCLUSION: This study identified multiple cases of WN allergy in young children in Korea, indicating that it is not rare. Co-sensitization and clinical adverse reactions between PN and WN suggests that more investigations are needed to conclude cross-reactivity between PN and WN.
Aged ; Anaphylaxis ; Angioedema ; Asia ; Child ; Female ; Food Hypersensitivity ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Juglans ; Korea ; Male ; Mass Screening ; Nuts ; Statistics as Topic ; Urticaria

PURPOSE: To investigate the clinical use of low-dose multidetector row computed tomography (MDCT) for staging of invasive breast cancers with patients in the prone position. METHODS: Three hundred twenty-two patients with 334 pathologically-verified breast cancers had low-dose MDCT breast imaging in the prone position for tumor staging before treatment between May 2006 and June 2010. We designed an additional computed tomography table pad with a hole for prone positioning. Patients lay prone on the table pad and the breasts were positioned within the rectangular hole. We obtained dynamic breast imaging from the lower neck to the lung base with the following parameters: 120 kVp, 50 mAs, and 3-mm reconstruction intervals. We evaluated the extent of the primary tumor, lymph nodal status, and distant metastasis in lung or bone, then assessed tumor staging based on the TNM classification of breast cancer. The assessed staging compared to the pathologic results for diagnostic accuracy. RESULTS: Among the 334 invasive breast cancers, the overall diagnostic accuracy of tumor staging was 88.3% and the accuracy values of each tumor stage were 89.6% in T1, 90.8% in T2, 81.0% in T3, and 89.3% in T4. The overall diagnostic accuracy of lymph nodal staging was 86.3% and the accuracy values in each nodal stage were 82.9% in N0, 88.0% in N1, 89.7% in N2, and 93.3% in N3. Based on breast computed tomography scans, we detected distant metastases in 30 cases (7 lungs, 10 bones, 7 lungs and bones, and 6 livers). CONCLUSION: Low-dose MDCT scanning for invasive breast cancer patients in the prone position is a feasible imaging technique for tumor staging before treatment to evaluate primary breast tumors, lymph nodes, lungs, or thoracic bones with reduced radiation doses.
Breast ; Breast Neoplasms ; Humans ; Lung ; Lymph Nodes ; Multidetector Computed Tomography ; Neck ; Neoplasm Metastasis ; Neoplasm Staging ; Prone Position

No abstract available.

PURPOSE: This study was object to the effects of a resistance exercise combined with relaxation therapy on blood pressure, frequency of exercise and physical fitness in elderly women. METHODS: Seventy three elderly women participated in an exercise program for 12 months. The exercise program consisted of stretching, massage and resistance training using thera-bands twice a week and 50 minutes in every sessions each week. Repeated measures ANOVA were performed using SAS. RESULTS: After the exercise program there was a significant difference in systolic blood pressure, frequency of exercise, body fat, sitting to standing, walking 2 minutes, sitting on a chair and reaching, and standing on one leg with eyes opened. After 6 months, there was a significant decrease in systolic blood pressure and significant increase in frequency of exercise, body fat, sitting to standing and standing on one leg with eyes opened. In 12 months, there was a significant increase in body fat, 2 minutes walking, and sitting in a chair and reaching. CONCLUSION: Resistance exercise combined with muscle relaxation therapy would have a positive effect on elderly women. We found that it was helpful for the elderly women in terms of physical fitness.
Adipose Tissue ; Aged ; Blood Pressure ; Eye ; Female ; Humans ; Leg ; Massage ; Muscle Relaxation ; Phenothiazines ; Physical Fitness ; Relaxation Therapy ; Resistance Training ; Walking

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is not commonly used in the colorectal area because of technical difficulty and due to the characteristics of the organ. We therefore wanted to determine the efficacy and safety of endoscopic submucosal dissection in colorectal neoplasms. METHODS: Colorectal tumor lesions resected by ESD in a single medical center were analyzed retrospectively. RESULTS: A total of 47 patients were treated for 50 lesions. Mean age was 64.3+/-9.8 (43~85) years. Laterally spreading tumors were the most common type (44, 88%) followed by Is+IIa type tumors (6, 12%). The en bloc resection rate was 76% and the complete resection rate was 74%. The mean procedure time was 81.1+/-44.7 (20~180) minutes. The mean size of resected specimen was 26.9+/-10.4 (10~50) mm. The histological diagnosis determined that 24 lesions (48%) were tubular adenoma, 18 lesions (36%) were intramucosal cancer, 7 lesions (14%) were sm1 cancer and 1 lesion (2%) was over sm2 cancer. Bleeding occurred in 6 (12%) and perforations in 13 (26%) of the patients and all were treated successfully by endoscopic or conservative treatment. The concordance rate of pre and post ESD pathological diagnosis was only 47%. CONCLUSIONS: ESD is a feasible technique for treating superficial colorectal tumors with a high complete resection rate, minor invasiveness, and a high safety rate. In addition, ESD might be useful in establishing the complete pathological evaluation of colorectal epithelial neoplasm.
Adenoma ; Colorectal Neoplasms ; Hemorrhage ; Humans ; Neoplasms, Glandular and Epithelial ; Retrospective Studies