The type III histone deacetylase silent information regulator 1 (SIRT1) is an enzyme that is critical for the modulation of immune and inflammatory responses. However, the data on its role in rheumatoid arthritis (RA) are limited and controversial. To better understand how SIRT1 regulates adaptive immune responses in RA, we evaluated collagen-induced arthritis (CIA) in myeloid cell-specific SIRT1 knockout (mSIRT1 KO) and wild-type (WT) mice. Arthritis severity was gauged on the basis of clinical, radiographic and pathologic scores. Compared with their WT counterparts, the mSIRT1 KO mice exhibited less severe arthritis, which was less destructive to the joints. The expression levels of inflammatory cytokines, matrix metalloproteinases and ROR-γT were also reduced in the mSIRT1 KO mice compared with the WT mice and were paralleled by reductions in the numbers of Th1 and Th17 cells and CD80- or CD86-positive dendritic cells (DCs). In addition, impaired DC maturation and decreases in the Th1/Th17 immune response were observed in the mSIRT1 KO mice. T-cell proliferation was also investigated in co-cultures with antigen-pulsed DCs. In the co-cultures, the DCs from the mSIRT1 KO mice showed decreases in T-cell proliferation and the Th1/Th17 immune response. In this study, myeloid cell-specific deletion of SIRT1 appeared to suppress CIA by modulating DC maturation. Thus, a careful investigation of DC-specific SIRT1 downregulation is needed to gauge the therapeutic utility of agents targeting SIRT1 in RA.
Animals ; Arthritis ; Arthritis, Experimental* ; Arthritis, Rheumatoid ; Coculture Techniques ; Cytokines ; Dendritic Cells* ; Down-Regulation ; Histone Deacetylases ; Joints ; Matrix Metalloproteinases ; Mice* ; T-Lymphocytes ; Th17 Cells

OBJECTIVE: Resveratrol is well-known for its anti-inflammatory, anti-oxidant effects on several diseases. We investigated whether dietary supplementation with resveratrol may suppress joint inflammation and destruction in a mouse model of collagen-induced arthritis (CIA). METHODS: Mice were randomly divided into two groups; CIA mice with normal diet-fed and CIA mice fed a 0.05% resveratrol diet. The effect of resveratrol on arthritis was assessed by clinical scoring system. The plain radiographs of paws were obtained to evaluate the effects on preventing bone destruction. Joint inflammation, cartilage damage, and osteoclastic bone resorption were checked by staining with H&E, Safranin-O, and tartrate resistant acid phosphatase (TRAP). Levels of pro-inflammatory cytokines were checked by enzyme-linked immunosorbent assay. The level of expression of nuclear factor (NF)-kappaB was measured by electrophoretic mobility shift assay (EMSA). RESULTS: Dietary supplementation with resveratrol led to mitigated severity of arthritis compared to the normal diet group (6.7+/-0.8 vs. 2.7+/-0.6, p<0.01). Resveratrol-fed mice showed decreased bone destruction on radiograph (3.4+/-0.3 vs. 2.0+/-0.2, p<0.01), and showed significantly inhibited pathological changes (inflammation 2.0+/-0.3 vs.3.2+/-0.2, p<0.01; cartilage damage 1.5+/-0.3 vs. 3.2+/-0.2, p<0.01; pannus formation 1.4+/-0.3 vs. 3.0+/-0.3, p<0.01; erosion; 1.4+/-0.2 vs. 3.3+/-0.3, p<0.01). Generation of TRAP-positive osteoclasts was inhibited in the resveratrol-fed mice (55.3+/-12.7 vs. 3.27+/-0.8, p<0.01). Resveratrol-fed mice showed decreased levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6,monocyte chemoattractant protein 1, and the soluble receptor activator of NF-kappaB ligand in joint tissues and sera. Expression of NF-kappaB, measured by EMSA, was decreased in resveratrol-fed mice. CONCLUSION: Dietary supplementation with resveratrol mitigates inflammation and bone destruction in CIA mice.
Acid Phosphatase ; Animals ; Antioxidants ; Arthritis ; Arthritis, Experimental* ; Arthritis, Rheumatoid* ; Bone Resorption ; Cartilage ; Cytokines ; Diet ; Dietary Supplements* ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Inflammation ; Interleukins ; Joints ; Mice ; NF-kappa B ; Osteoclasts ; Receptor Activator of Nuclear Factor-kappa B ; Tumor Necrosis Factor-alpha

BACKGROUND: Early prediction of neurologic outcome is important to patients treated with therapeutic hypothermia after hypoxic brain injury. Hypoxic brain injury patients may have poor neurologic prognosis due to increased intracranial pressure. Increased intracranial pressure can be detected by optic nerve sheath diameter (ONSD) measurement in computed tomography (CT) or ultrasound. In this study, we evaluate the relation between neurologic prognosis and optic nerve sheath diameter measured in brain CT of hypoxic brain injury patients. METHODS: We analyzed the patient clinical data by retrospective chart review. We measured the ONSD in initial brain CT. We also measured and calculated the gray white matter ratio (GWR) in CT scan. We split the patients into two groups based on neurologic outcome, and clinical data, ONSD, and GWR were compared in the two groups. RESULTS: Twenty-four patients were included in this study (age: 52.6 +/- 18.3, 18 males). The mean ONSD of the poor neurologic outcome group was larger than that of the good neurologic outcome group (6.07 mm vs. 5.39 mm, p = 0.003). The GWR of the good neurologic outcome group was larger than that of the poor outcome group (1.09 vs. 1.28, p = 0.000). ONSD was a good predictor of neurologic outcome (area under curve: 0.848), and an ONSD cut off > or = 5.575 mm had a sensitivity of 86.7% and a specificity of 77.8%. CONCLUSIONS: ONSD measured on the initial brain CT scan can predict the neurologic prognosis in cardiac arrest and hanging patients treated with therapeutic hypothermia.
Brain Injuries ; Brain* ; Heart Arrest* ; Humans ; Hypothermia ; Intracranial Pressure ; Optic Nerve* ; Prognosis* ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Ultrasonography

PURPOSE: To evaluate clinical predictors of cervical abscess in adult patients who present a sore throat. METHODS: We prospectively studied adult patients (18 years of age or older) who presented with a sore throat at one of three hospitals (Chungnam national university hospital, Chungbuk national university hospital, and Konyang university hospital) from June 2010 to June 2011. The enrolled patients received a neck computed tomography scan, and their clinical manifestations were investigated. We evaluated several clinical variables in order to predict the existence of cervical abscess by use of multiple logistic regression analysis, and assessed the ability of the results of these variables to accurately diagnose cervical abscess using a receiver operating characteristic curve. RESULTS: A total of 109 patients were enrolled in this study. We identified two clinical variables (swelling and voice change) useful in predicting the existence of cervical abscess, and the AUC acquired by adding the scores of the two clinical factors was 0.89 (p<0.01). The sensitivity and specificity of these clinical factors to predict cervical abscess were 0.96 and 0.69 when the cut off value was determined to be 2. CONCLUSION: Two clinical factors (swelling and voice change) were useful in predicting the appearance of cervical abscesses. Consideration should be made for the need for incision and drainage of a cervical abscess if a patient presents swelling, or swelling and voice change.
Abscess ; Adult ; Area Under Curve ; Drainage ; Emergencies ; Humans ; Logistic Models ; Neck ; Pharyngitis ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Voice

PURPOSE: To evaluate clinical predictors of cervical abscess in adult patients who present a sore throat. METHODS: We prospectively studied adult patients (18 years of age or older) who presented with a sore throat at one of three hospitals (Chungnam national university hospital, Chungbuk national university hospital, and Konyang university hospital) from June 2010 to June 2011. The enrolled patients received a neck computed tomography scan, and their clinical manifestations were investigated. We evaluated several clinical variables in order to predict the existence of cervical abscess by use of multiple logistic regression analysis, and assessed the ability of the results of these variables to accurately diagnose cervical abscess using a receiver operating characteristic curve. RESULTS: A total of 109 patients were enrolled in this study. We identified two clinical variables (swelling and voice change) useful in predicting the existence of cervical abscess, and the AUC acquired by adding the scores of the two clinical factors was 0.89 (p<0.01). The sensitivity and specificity of these clinical factors to predict cervical abscess were 0.96 and 0.69 when the cut off value was determined to be 2. CONCLUSION: Two clinical factors (swelling and voice change) were useful in predicting the appearance of cervical abscesses. Consideration should be made for the need for incision and drainage of a cervical abscess if a patient presents swelling, or swelling and voice change.
Abscess ; Adult ; Area Under Curve ; Drainage ; Emergencies ; Humans ; Logistic Models ; Neck ; Pharyngitis ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Voice

OBJECTIVE: Angiopoietin-1 (Ang1) is a potent angiogenic factor that can increase synovial angiogenesis and also enhance osteoblast maturation and bone formation. However, its role in rheumatoid arthritis (RA) has not been well documented. Thus, we investigated roles of Ang1 in collagen-induced arthritis (CIA). METHODS: A recombinant adenovirus carrying the gene that encodes either cartilage oligomeric matrix protein (AdCOMP)-Ang1 (a modified form of Ang1) or LacZ (AdLacZ) was injected intravenously into CIA mice. Clinical, radiological, histopathological, and immunofluorescent analyses were performed. Serum levels of receptor activators of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) and expression of osteoblast maturation genes were analyzed. RESULTS: AdCOMP-Ang1-injected mice developed more severe inflammation than the AdLacZ-injected mice. However, there were no significant differences in cartilage damage and bone erosion. More PECAM-1-positive blood vessels were seen in the synovium of the AdCOMP-Ang1-injected mice than in those injected with AdLacZ. Interestingly, a lower number of TRAP-positive osteoclasts were observed in AdCOMP-Ang1-injected CIA mice than in the AdLacZ group when comparing sections obtained from joints showing similar synovial proliferation. The serum OPG/RANKL ratio and expression of osteoblast maturation genes, such as runt-related transcription factor 2, bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the AdCOMP-Ang1 group. CONCLUSION: COMP-Ang1 facilitates arthritis onset and increases synovial inflammation, but enhances osteoblast maturation, which in turn inhibits osteoclastogenesis by increasing the OPG/RANKL ratio in CIA. Our results suggest that careful investigation is necessary to delineate the possible therapeutic use of COMP-Ang1 as an adjunctive agent, in combination with anti-inflammatory therapies, for the prevention of bone destruction in RA.
Adenoviridae ; Angiogenesis Inducing Agents ; Angiopoietin-1 ; Animals ; Arthritis ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Blood Vessels ; Cartilage ; Collagen Type I ; Extracellular Matrix Proteins ; Glycoproteins ; Inflammation ; Integrin-Binding Sialoprotein ; Joints ; Lifting ; Mice ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteopontin ; Osteoprotegerin ; Synovial Membrane ; Transcription Factors

PURPOSE: We evaluated the safety of bolus infusion through intraosseous access using the EZ-IO in adults in terms of extraosseous flow. METHODS: We conducted a prospective study of adults (over age 18) in whom intraosseous access through the tibia was performed by emergency physicians or residents from June 2010 to June 2011. We used ultrasonography to confirm extraosseous flow during infusion of 80 mL normal saline with a 4 mL/s flow rate through intraosseous access, immediately after confirmation of intraosseous needle insertion using conventional methods. Finally, we recorded any complications that occurred immediately in the area of intraosseous access. RESULTS: Of 30 patients enrolled in the study, 22(73.3%) were male and eight (26.7%) were female. The mean age of study participants was 62.78+/-15.68 years; mean cortical thickness of participants' tibias was 0.27+/-0.03 cm. The mean time required for performance of the intraosseous access procedure was 16.00+/-4.65 s; success rate on the first attempt, 100.0%. No immediate complications, including swelling or extraosseous flow at the area of intraosseous access, were observed. CONCLUSION: In this study, bolus infusion though intraosseous access using the EZ-IO in adults in emergency departments was a safe option in terms of extraosseous flow.
Adult ; Emergencies ; Female ; Humans ; Male ; Needles ; Prospective Studies ; Tibia

Anesthesia, General ; Animals ; Azaperone ; Durapatite ; Humans ; Osteoblasts ; Osteogenesis ; Polyethylenes ; Polypropylenes ; Seeds ; Swine

We report the case of a 23-year-old woman who developed bowenoid papulosis of the vulva and subsequent periungual Bowen's disease. She had a history of a long standing periungual wart on her right thumb before the outbreak of periungual Bowen's disease. By HPV DNA chip, human papillomavirus (HPV) 11, 18 and 31 were identified from the periungual lesions, and HPV 11, 18 and 33 from the vulvar lesion. This case supports the theory of anogenital-digital spread of HPV, and proposes that the periungual wart may change into Bowen's disease by mucosal HPVs. To the best of our knowledge, this case is important as the first Korean case of periungual Bowen's disease concurrent with bowenoid papulosis of the vulva.
Bowen's Disease ; Female ; Human papillomavirus 11 ; Humans ; Oligonucleotide Array Sequence Analysis ; Thumb ; Vulva ; Warts ; Young Adult

PURPOSE: To determine the accuracy of a simple radiologic images as a diagnostic tool for intra-articular fractures of the distal radius (IAF). METHODS: This study proceeded prospectively from April 2008 to December 2009. We let 25 ERs (emergency residents) interpret the radiologic images of 45 patients who had injuries of their wrists and presented to a hospital. We used surgical findings or multidetector computed tomography (MDCT) to confirm the final diagnosis of enrolled patients. Finally, we evaluated the sensitivity, specificity, and accuracy of simple radiologic images of IAF. We also compared test performance characteristics between the four grades of the ERs (1st, 2nd, 3rd, and 4th years) via Mann-Whitney and Kruskal-Wallis tests. We considered differences to be significant, if p<0.05 RESULTS: Of 45 patients, 40 (88.9%) had fractures of the distal radius; of the 40, 25 (62.5%) had IAF. There were no differences in sensitivity, specificity, or accuracy between the four grades of the ERs (p=0.86, 0.76, 0.49). The sensitivity of simple radiologic images for diagnosing IAF was 0.69; specificity was 0.77; accuracy was 0.72. CONCLUSION: In this study, we found that simple radiologic images as the primary diagnostic tool for intra-articular fractures of the distal radius were not completely adequate. Therefore, ERs should carefully consider using MDCT imaging to diagnose patients who suffer from wrist pain.
Emergencies ; Humans ; Intra-Articular Fractures ; Linear Energy Transfer ; Multidetector Computed Tomography ; Prospective Studies ; Radius ; Radius Fractures ; Sensitivity and Specificity ; Wrist