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1.  Effect of the protein corona on nanoparticles for modulating cytotoxicity and immunotoxicity 
Although the cytotoxicity of nanoparticles (NPs) is greatly influenced by their interactions with blood proteins, toxic effects resulting from blood interactions are often ignored in the development and use of nanostructured biomaterials for in vivo applications. Protein coronas created during the initial reaction with NPs can determine the subsequent immunological cascade, and protein coronas formed on NPs can either stimulate or mitigate the immune response. Along these lines, the understanding of NP-protein corona formation in terms of physiochemical surface properties of the NPs and NP interactions with the immune system components in blood is an essential step for evaluating NP toxicity for in vivo therapeutics. This article reviews the most recent developments in NP-based protein coronas through the modification of NP surface properties and discusses the associated immune responses.
PMCID: PMC4275058  PMID: 25565807
nanostructured biomaterials; blood response; cytotoxicity; immunotoxicity; protein corona
2.  Ankylosing spondylitis with cervical fracture, cardiac arrest, locked-in syndrome and death 
BMJ Case Reports  2012;2012:bcr0120125522.
PMCID: PMC3416994  PMID: 22782997
3.  Assessment of mOMV adjuvant efficacy in the pathogenic H1N1 influenza virus vaccine 
Since the pandemic (H1N1) 2009 virus has been a seasonal flu which still poses great human health concerns worldwide, vaccination would be considered as the most effective strategy to control the influenza virus spreading. Here, we assessed adjuvant efficacy of modified outer membrane vesicle (mOMV) towards the pandemic H1N1 split antigen.
Materials and Methods
For this study, mice were vaccinated twice with various amount of antigen (0.05, 0.1, and 0.5 µg/dose hemagglutinin [HA]) that were mixed with mOMV, aluminum hydroxide (alum), and MF59, as well as the combined adjuvant comprising the mOMV plus alum.
We found that all the adjuvanted vaccines of A/California/04/09 (CA04, H1N1) containing HA antigen more than 0.1 µg/dose protected effectively from lethal challenge (maCA04, H1N1) virus, compared to the antigen only group. Furthermore, vaccinated mice received as low as 0.05 µg/dose of the split vaccine containing the combined adjuvant (10 µg of mOMV plus alum) showed a full protection against lethal challenge with H1N1 virus. Taken together, these results suggest that mOMV can exert not only the self-adjuvanticity but also a synergy effect for the vaccine efficacy when combined with alum.
Our results indicate that mOMV could be a promising vaccine adjuvant by itself and it could be used as a vaccine platform for development of various vaccine formulations to prepare future influenza pandemic.
PMCID: PMC4083072  PMID: 25003093
Influenza A virus; A/California/04/09 (CA04, H1N1); Adjuvant; mOMV
4.  Clinical Outcomes of Posterior C2-C3 Fixation for Unstable Hangman's Fracture Compared with Posterior C1-C3 Fusion 
Korean Journal of Spine  2014;11(2):33-38.
To verify the clinical outcomes of posterior C2-C3 fixation for unstable Hangman's fracture compared with posterior C1-C3 fixation.
Twenty four patients for unstable Hangman's fracture were enrolled between July 2007 and June 2010 in this study. Thirteen patients underwent posterior C2-C3 fusion and 11 patients underwent posterior C1-C3 fusion. Clinical outcomes were evaluated using Neck Disability Index (NDI) scores and Visual Analogue Scale (VAS) scores during preoperative and postoperative follow up period. Plain radiographs were obtained on postoperative 1 day, 1 week, and then at 1, 2, 6, and 12 months. CT was done at postoperative 12 months in all patients for evaluation of bone fusion. The mean period of clinical follow-up was 15 months.
The mean ages were 43.3 years in C2-C3 group and 50.0 years in C1-C3 group. Mean follow-up period was 17.2 months in C2-C3 group and 16.3 months in C1-C3 group. VAS scores and NDI scores in C2-C3 group were much less than those in C1-C3 group at each follow-up period. The differences of VAS score and NDI scores between C2-C3 and C1-C3 groups at each follow-up period were statistically significant (p<0.001) by paired T-test. Solid Bone fusion was confirmed in all cases at the final follow-up.
C2-C3 group showed better clinical and biomechanical results than C1-C3 group in terms of axial pain and disability of neck.
PMCID: PMC4124924  PMID: 25110480
Trauma; Spondylolisthesis; Fracture; Unstable; Posterior fixation
5.  Simultaneously Presented Acute Ischemic Stroke and Non-ST Elevation Myocardial Infarction in a Patient with Paroxysmal Atrial Fibrillation 
Korean Circulation Journal  2013;43(11):766-769.
Although atrial fibrillation is the most frequent cause of embolic stroke, coronary embolism from atrial fibrillation is a very rare cause of acute myocardial infarction. Therefore, simultaneously presented acute ischemic stroke and acute myocardial infarction due to atrial fibrillation in the same patient has not been documented. The present report describes the case of a 58-year-old man with paroxysmal atrial fibrillation who initially presented with a large cerebral infarction due to embolic occlusion of the left middle cerebral artery. Four hours after the diagnosis of cerebral embolism, he was subsequently diagnosed with acute myocardial infarction due to concurrent coronary embolism. He underwent successful coronary revascularization with a drug-eluting stent. The possibility of combined coronary embolism as a rare etiology should be kept in mind when a patient with acute embolic stroke presents, especially when there is evidence of acute myocardial infarction.
PMCID: PMC3866317  PMID: 24363753
Atrial fibrillation; Cerebral infarct; Embolism; Myocardial infarction; Percutaneous transluminal coronary angioplasty
6.  Posterior C2-C3 Fixation for Unstable Hangman's Fracture 
Korean Journal of Spine  2013;10(3):165-169.
This is a retrospective review of 13 unstable Hangman's fractures who underwent posterior C2-3 fixation to describe clinical outcomes with a literature review.
Thirteen patients for unstable Hangman's fracture were enrolled between July 2007 and June 2010 were included in this study. The medical records of all patients were reviewed. Concurrently, clinical outcomes were evaluated using Neck Disability Index (NDI) scores and Visual Analogue Scale (VAS) scores during preoperative and postoperative follow up period. Plain radiographs were obtained on postoperative 1day, 1week, and then at 1, 2, 6, and 12 months. CT was done at postoperative 12 months in all patients for evaluation of bone fusion. The mean period of clinical follow-up was 17 months.
Mean age were 43 years old. Bone fusion was recognized in all cases at the final follow-up. The average preoperative VAS score for neck pain was 8.3±1.1, while the final follow-up VAS score was 2.07±0.8 (p<0.001). The average immediate postoperative NDI was 84% points and final NDI was 22% points (p<0.001). There were one case of infection and 1 case of screw loosening.
In the treatment of the patients with unstable Hangman's fracture, posterior C2-C3 fusions is effective and curative treatments to achieve cervical spinal stability.
PMCID: PMC3941766  PMID: 24757480
Traumatic spondylolisthesis of the axis; Hangman's fracture; instability; C2; C3
7.  Current practice in hemodynamic monitoring and management in high-risk surgery patients: a national survey of Korean anesthesiologists 
Hemodynamic optimization improves postoperative outcomes in high-risk surgery patients. The monitoring of cardiac output (CO) and dynamic parameters of fluid responsiveness can guide hemodynamic optimization. We conducted a survey to assess the current hemodynamic monitoring and management practices of Korean anesthesiologists during high-risk surgery.
E-mails containing a link to our survey, which consisted of 33 questions relating to hemodynamic monitoring during high-risk surgery, were sent to 3,943 members of the Korean Society of Anesthesiologists (KSA). The survey web page was open from December 30, 2011 to March 31, 2012.
A total of 139 anesthesiologists responded during the survey period. Invasive arterial pressure (97.2%) and central venous pressure (93.4%) were routinely monitored. CO was monitored in 58.5% of patients; stroke volume variations were monitored in 50.9% of patients. However, CO was consistently optimized by < 20% of anesthesiologists. An arterial pressure waveform-derived CO monitor was the most frequently used device to monitor CO (79.0%). Blood pressure, urine output, central venous pressure, and clinical experience were considered to be the best indicators of volume expansion than CO or dynamic parameters of fluid responsiveness.
The survey revealed that KSA members frequently monitor CO and dynamic parameters of fluid responsiveness during high-risk surgery. However, static indices were used more often to judge volume expansion. The current study reveals that CO is not frequently optimized despite the relatively high incidence of CO monitoring during high-risk surgery in Korea.
PMCID: PMC3726841  PMID: 23904935
Cardiac output; Hemodynamics; Intraoperative; Monitoring; Treatment outcome
8.  The comparative immunotoxicity of mesoporous silica nanoparticles and colloidal silica nanoparticles in mice 
Mesoporous silica (MPS) nanoparticles (NPs), which have a unique pore structure and extremely large surface area and pore volume, have received much attention because of their biomedical application potential. Using MPS NPs for biomedical devices requires the verification of their biocompatibility because the surface area of NPs is one of the most important determinants of toxicity, including the cellular uptake and immune response. We have previously reported that the cytotoxicity and inflammation potential of MPS NPs have been shown to be lower than those of general amorphous colloidal silica (Col) NPs in macrophages, but the low cytotoxicity does not guarantee high biocompatibility in vivo. In this study, we compared the in vivo immunotoxicity of MPS and Col NPs in the mouse model to define the effects of pore structural conditions of silica NPs.
Materials and methods
Both MPS and Col NPs (2, 20, and 50 mg/kg/day) were intraperitoneally administered in female BALB/c mice for 4 weeks, and clinical toxicity, lymphocyte population, serum IgG/IgM levels, and histological changes were examined.
There was no overt sign of clinical toxicity in either MPS- or Col-treated mice. However, MPS NPs led to significant increases in liver and spleen weight and splenocyte proliferation. Mice treated with MPS NPs showed altered lymphocyte populations (CD3+, CD45+, CD4+, and CD8+) in the spleen, increased serum IgG and IgM levels, and histological changes. Despite slight changes in lymphocyte populations in the spleen, Col NPs did not alter other immunological factors.
The results indicate that in vivo exposure to MPS NPs caused more damage to systemic immunity than that of Col NPs through the dysregulation of the spleen. The results for in vivo data are inconsistent with those for in vitro data, which show lower cytotoxicity for MPS NPs. These results suggest the importance of verifying biocompatibility both in vitro and in vivo during the design of new nanomaterials.
PMCID: PMC3544348  PMID: 23326190
immunotoxicity; mesoporous silica nanoparticle; colloidal silica nanoparticle; spleen
9.  Brachial Plexus Tumors in a Consecutive Series of Twenty One Patients 
This is a retrospective review of 22 surgically treated benign and malignant tumors of brachial plexus region to describe clinical presentation, the characteristics of brachial plexus tumor and clinical outcomes with a literature review.
Twenty-one patients with consecutive 22 surgeries for primary brachial plexus tumors were enrolled between February 2002 and November 2011 were included in this study. The medical records of all patients were reviewed.
Eleven male and 10 female patients were enrolled. Mean age was 39 years. Three patients had brachial plexus tumor associated with neurofibromatosis (13.6%). Presenting signs and symptoms included parenthesis and numbness (54.5%), radiating pain (22.7%), direct tenderness and pain (27.2%), palpable mass (77.3%). Twelve patients presented preoperative sensory deficit (54.5%) and 9 patients presented preoperative motor deficit (40.9%). Twenty tumors (90.9%) were benign and 2 tumors (9.1%) were malignant. Benign tumors included 15 schwannomas (68.2%), 4 neurofibromas (18.2%) and 1 granular cell tumor (4.5%). There were 1 malignant peripheral nerve sheath tumor (MPNST) and 1 malignant granular cell tumor. Gross total resection was achieved in 16 patients (72.7%), including all schwannomas, 1 neurofibroma. Subtotal resection was performed in 6 tumors (27.3%), including 3 neurofibromatosis associated with brachial plexus neurofibromas, 1 MPNST and 2 granular cell tumor in one patient.
Resection of tumor is the choice of tumor in the most of benign and malignant brachial plexus tumors. Postoperative outcomes are related to grade of resection at surgery and pathological features of tumor.
PMCID: PMC3467372  PMID: 23091673
Brachial plexus tumor; Nerve sheath tumor; Schwannoma; Neurofibroma; Granular cell tumor
10.  Clinical Outcomes of Percutaneous Plasma Disc Coagulation Therapy for Lumbar Herniated Disc Diseases 
This is prospective study of clinical outcomes of percutaneous plasma disc coagulation Therapy (PDCT) in patients with herniated lumbar disc disease (HLD) to evaluate the safety and efficacy in its clinical application and usefulness as a reliable alternative to microscopic discectomy.
Forty-six patients were enrolled in this study from April 2006 to June 2010. All patients had one-level HLD. Disc degeneration was graded on routine T2-weighted magnetic resonance Image (MRI) using the Pfirrmann's grading system and all index levels were grade 3 and grade 4. Indications for surgery were radiculopathy caused by disc protrusion with soft consistency. MRI was done at one month after the procedure in all patients to check post-PDCT change. The clinical outcomes were evaluated using Visual Analog Scales (VAS) score and MacNab's criteria.
This study was approved by the Institutional Review Board of our institution. The age of the study population ranged from 16 to 59 years with a mean age of 37.2 years. There were 29 males and 17 females in this study. The mean period of clinical follow-up was 21 months. The average preoperative VAS score for radiculopathy was 7.4±1.4, while the final follow-up VAS score was 1.4±0.7 (p<0.001). In MacNab's criteria, 41 patients (89.1%) had achieved favorable improvement (excellent and good) until later follow-up. There were one patient from infection and two patients who needed to convert to open discectomy.
PDCT is a safe and efficient treatment modality in a selective patient with HLD.
PMCID: PMC3291713  PMID: 22396836
Intradiscal; PDCT; Herniated lumbar disc; Disc coagulation
11.  Two Separate Episodes of Intramedullary Spinal Cord Metastasis in a Single Patient with Breast Cancer 
Intramedullary spinal cord metastases are very rare. Patients with breast cancer as the primary source of intramedullary spinal cord metastases tend to do better than other types of cancer. We report the very unusual case of a woman with breast cancer who had two separate episodes of intramedullary spinal cord metastasis.
PMCID: PMC2941861  PMID: 20856667
Intramedullary; Cervical; Thoracolumbar; Metastases; Breast cancer; Surgical treatment
12.  Prophylactic effect of dexamethasone in reducing postoperative sore throat 
This study was performed to compare the effectiveness of prophylactic dexamethasone and postintubation dexamethasone in reducing the incidence and severity of postoperative sore throat (POST).
This was a prospective, randomized, double-blind clinical trial. The study population consisted of 70 patients between 20 and 60 years old who were classified as American Society of Anesthesiologists I-II and were scheduled for elective laparoscopic cholecystectomy. The patients were divided randomly into two groups. Patients in the prophylactic and postintubation groups received intravenous injection of 10 mg of dexamethasone 30 min before or after tracheal intubation, respectively. The patients were interviewed 1, 6, and 24 h after the operation. The incidence and severity of POST were recorded.
The severity scores of POST at 1 and 6 h after the operation were significantly lower in the prophylactic group than in the postintubation group. There were no significant differences in the incidence of POST during the 24 h after the operation between the two groups (22/32 in the prophylactic group vs. 27/34 in the postintubation group, P = 0.403).
Intravenous injection of 10 mg of dexamethasone was more effective in reducing the severity of POST when administered before tracheal intubation compared with after tracheal intubation.
PMCID: PMC2872887  PMID: 20498806
Cholecystectomy; Complications; Dexamethasone; Intubation tracheal; Laparoscopic
14.  Clinical and Radiological Outcomes of Anterior Cervical Interbody Fusion Using Hydroxyapatite Spacer 
This is retrospective study of clinical and radiological outcomes of anterior cervical fusion using Bongros-HA™ (BioAlpha, Seongnam, Korea) which is a type of synthetic hydroxyapatite (HA) spacer to evaluate the efficacy in its clinical application and usefulness as a reliable alternative to autograft bone.
Twenty-nine patients were enrolled in this study and 40 segments were involved. All patients were performed anterior cervical interbody fusion using HA spacer and plating system. Indications for surgery were radiculopathy caused by soft-disc herniation or spondylosis in 18 patients, spondylotic myelopathy in 1 patient, and spinal trauma in 10 patients. Cervical spine radiographs were obtained on postoperative 1day, 1week, and then at 1, 2, 6, and 12 months in all patients to evaluate intervertebral disc height, and the degrees of lordosis. Cervical computed tomography was done at postoperative 12 month in all patients to confirm the fusion status. The mean period of clinical follow-up was 17 months.
Complete interbody fusion was achieved in 100% of patients. Preoperative kyphotic deformities were corrected in all cases after surgery. Intervertebral disc height was well maintained during follow up period. There were no cases of graft extrusion, graft deterioration and graft fracture.
HA spacer is very efficient in achieving cervical fusion, maintaining intervertebral disc height, and restoring lordosis. When combined with the placement of a cervical plate, immediate stability can be achieved and graft related complication can be prevented.
PMCID: PMC2773384  PMID: 19893716
Hydroxyapatite; Spacer; Anterior cervical discectomy; Fusion; Graft; Plate
15.  Chordomas Involving Multiple Neuraxial Bones 
We present a patient with multifocal symptomatic osseous chordomas having unusual growth patterns with review of the pertinent literature. The patient was 62-year-old male and had multiple osseous chordomas located in sacral, thoracic, and paraclival jugular foramen areas. There was no metastasis in other organs. All affected sites were osseous. The multicentric chordomas are extremely rare. This case could be considered as a chordoma involving multiple neuraxial bones. But, the possibility of multicentricity could also be thought. In such cases radical resection should be performed for each lesion at the initial diagnosis. If complete surgical resections are infeasible or impossible, preoperative or postoperative radiation therapy should be planned for the highest possibility of successful treatment.
PMCID: PMC2640821  PMID: 19242569
Chordoma; Multiple; Thoracic; Sacral; Paraclival; Jugular foramen
16.  Abdominal Ultrasonography Findings in Patients with Spinal Cord Injury in Korea 
Journal of Korean Medical Science  2006;21(5):927-931.
This is a retrospective study of 500 patients with spinal cord injury who underwent abdominal ultrasonography as a routine screening test from 2000 to 2003. We analyzed the results according to the different abdominal organ systems. Among the 500 cases, 226 (45.2%) showed abnormal findings. 98 cases of abnormal findings in the liver included 75 of fatty liver and 13 of mass. The 88 cases of abnormal findings in the bladder included 56 of bladder wall thickening, 14 of cystitis and 10 of urinary stone. The 35 cases of abnormal findings in the kidney included 19 of renal cyst and 6 of pelvic dilatation. The 35 cases with gallbladder abnormalities included 19 with gallstones and 11 with biliary sludge. Excluding the cases with bladder wall thickening, there were still 170 cases with abnormal ultrasonographic findings. Abdominal sonography seems to be a useful tool in detecting hidden intraabdominal pathologies in patients with spinal cord injury.
PMCID: PMC2722007  PMID: 17043431
Ultrasonography; Spinal Cord Injuries; Gallstones; Cholelithiasis; Bladder
17.  Infected Pneumatocele Following Anaerobic Pneumonia in Adult 
We report a case of an infected pneumatocele in the course of anaerobic pneumonia in an adult. To the best of our knowledge, anaerobic pneumonia complicated by a pneumatocele in an adult has not previously been described. The pneumatocele occurred on the fifth day of hospitalization, and rapidly increased in size, with the development of a subsequent mixed anaerobe infection. A pig-tail catheter was inserted and the pus drained. The bacterial culture from the pus was positive for three anaerobes: Bacteroid species, Peptostreptococcus asaccharolyticus and Fusobacterium species. Intravenous antibiotics and percutaneous catheter drainage resulted in a successful treatment.
PMCID: PMC3891083  PMID: 16491835
Pneumatocele; Infected pneumatocele; Anaerobic pneumonia
18.  Biologic Response of Degenerative Living Human Nucleus Pulposus Cells to Treatment with Cytokines 
Yonsei Medical Journal  2014;56(1):277-286.
To investigate the molecular responses of various genes and proteins related to disc degeneration upon treatment with cytokines that affect disc-cell proliferation and phenotype in living human intervertebral discs (IVDs). Responsiveness to these cytokines according to the degree of disc degeneration was also evaluated.
Materials and Methods
The disc specimens were classified into two groups: group 1 (6 patients) showed mild degeneration of IVDs and group 2 (6 patients) exhibited severe degeneration of IVDs. Gene expression was analyzed after treatment with four cytokines: recombinant human bone morphogenic protein (rhBMP-2), transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Molecular responses were assessed after exposure of cells from the IVD specimens to these cytokines via real-time polymerase chain reaction and immunofluorescence staining.
mRNA gene expression was significantly greater for aggrecan, type I collagen, type II collagen, alkaline phosphatase, osteocalcin, and Sox9 in group 1 than mRNA gene expression in group 2, when the samples were not treated with cytokines. Analysis of mRNA levels for these molecules after morphogen treatment revealed significant increases in both groups, which were much higher in group 1 than in group 2. The average number of IVD cells that were immunofluorescence stained positive for alkaline phosphatase increased after treatment with rhBMP-2 and TGF-β in group 1.
The biologic responsiveness to treatment of rhBMP-2, TGF-β, TNF-α, and IL-1β in the degenerative living human IVD can be different according to the degree of degeneration of the IVD.
PMCID: PMC4276767  PMID: 25510775
Cytokine; disc degeneration; rhBMP-2; TGF-β; TNF-α; IL-1β
19.  Pig Spermatozoa Defect in Acrosome Formation Caused Poor Motion Parameters and Fertilization Failure through Artificial Insemination and In vitro Fertilization 
The selection of morphologically normal spermatozoa is critical to obtain high breeding performances in boar breeding farms and artificial insemination (AI) centers. Parameters for the selection of semen mainly include total sperm motility, concentration, and morphology. However, these primary parameters are often not reliable for discriminating between normal and abnormal, non-fertilizable spermatozoa. The present study was designed to compare the motion characteristics, fertilization ability using in vitro fertilization (IVF), and acrosome formation of the semen from boars having low (boar number 2012) and normal (boar number 2004 and 2023) breeding performances. The ultimate goal was to identify additional simple and easy criteria for the selection of normal sperm. There was no significant difference between boar 2004 and boar 2023 sperm total motility in computer assisted sperm analysis. However, boar number 2012 semen presented a significantly reduced population of rapid moving spermatozoa and an increased population of slow moving spermatozoa compared to boar numbers 2004 and 2023. Analysis of detailed motion characteristics revealed that sperm from boar number 2012 had significantly reduced motility in progressiveness, average path velocity, straight-line velocity (VSL), curvilinear velocity (VCL), straightness, and linearity. The assessment of the fertilizing ability by IVF also showed that sperm from boar number 2012 showed a fertility rate of 3.4%, whereas sperm from boar number 2023 had a fertility rate of 75.45%. Interestingly, most of the sperm nuclei were found on the peripheral area of the oocytes, suggesting that the sperm from boar number 2012 lacked penetration ability into the oocyte zonapellucida. The acrosome formation analysis using Pisum sativum agglutinin staining demonstrated that the sperm from boar number 2012 had a defect in acrosome formation. Consequently, primary parameters for selecting semen before AI such as motility are not sufficient to select normal and fertilizable spermatozoa. In conclusion, the present study suggests that the acrosome staining and detailed motion characteristics such as progressiveness, VCL, and VSL should be included in determining semen quality together with primary parameters for successful AI and high breeding performance in the swine industry.
PMCID: PMC4150174  PMID: 25178293
Boar; Sperm; Motion Parameters; In vitro Fertilization; Acrosome Defect
20.  The incidence and predictors of overall adverse effects caused by low dose amiodarone in real-world clinical practice 
Most current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size.
Between January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of discontinuation or drug dose reduction due to an unexpected clinical response.
The mean daily dose of amiodarone was 227 ± 126 mg, and the mean duration was 490 ± 812 days. During the mean follow-up duration of 982 ± 1,137 days, a total of 154 patients (16.6%) experienced adverse effects related to amiodarone, the most common being bradycardia or conduction disturbance (9.5%). Major organ toxicities in the thyroid (2.5%), liver (2.2%), eyes (0.6%), and lungs (0.3%) were rare. All patients recovered fully without complications after amiodarone discontinuation or dose reduction. The only independent predictor of adverse effects was the duration of amiodarone treatment (odds ratio, 1.21; 95% confidence interval, 1.03 to 1.41; p = 0.016, per year).
Low-dose amiodarone is well tolerated in a real-world clinical population. Further studies with a prospective design are needed to confirm this finding.
PMCID: PMC4164722  PMID: 25228834
Adverse effects; Amiodarone; Incidence; Risk factors
21.  Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles 
PLoS ONE  2014;9(7):e100229.
We investigated whether eyedrop vaccination using modified outer membrane vesicles (mOMVs) is effective for protecting against hemolytic uremic syndrome (HUS) caused by enterohemorrhagic E. coli (EHEC) O157:H7 infection. Modified OMVs and waaJ-mOMVs were prepared from cultures of MsbB- and Shiga toxin A subunit (STxA)-deficient EHEC O157:H7 bacteria with or without an additional waaJ mutation. BALB/c mice were immunized by eyedrop mOMVs, waaJ-mOMVs, and mOMVs plus polymyxin B (PMB). Mice were boosted at 2 weeks, and challenged peritoneally with wild-type OMVs (wtOMVs) at 4 weeks. As parameters for evaluation of the OMV-mediated immune protection, serum and mucosal immunoglobulins, body weight change and blood urea nitrogen (BUN)/Creatinin (Cr) were tested, as well as histopathology of renal tissue. In order to confirm the safety of mOMVs for eyedrop use, body weight and ocular histopathological changes were monitored in mice. Modified OMVs having penta-acylated lipid A moiety did not contain STxA subunit proteins but retained non-toxic Shiga toxin B (STxB) subunit. Removal of the polymeric O-antigen of O157 LPS was confirmed in waaJ-mOMVs. The mice group vaccinated with mOMVs elicited greater humoral and mucosal immune responses than did the waaJ-mOMVs and PBS-treated groups. Eyedrop vaccination of mOMVs plus PMB reduced the level of humoral and mucosal immune responses, suggesting that intact O157 LPS antigen can be a critical component for enhancing the immunogenicity of the mOMVs. After challenge, mice vaccinated with mOMVs were protected from a lethal dose of wtOMVs administered intraperitoneally, conversely mice in the PBS control group were not. Collectively, for the first time, EHEC O157-derived mOMV eyedrop vaccine was experimentally evaluated as an efficient and safe means of vaccine development against EHEC O157:H7 infection-associated HUS.
PMCID: PMC4102476  PMID: 25032703
22.  Acetabular Paralabral Cyst as a Rare Cause of Obturator Neuropathy: A Case Report 
Annals of Rehabilitation Medicine  2014;38(3):427-432.
An acetabular paralabral cyst is a benign soft tissue cyst usually seen in association with a tear of the acetabular labrum. Acetabular paralabral cysts are often the cause of joint pain, but they rarely cause compression of the adjacent neurovascular structures. We present a case of a 63-year-old male patient who had paresis and atrophy of right hip adductor muscles. Right obturator neuropathy was confirmed through an electrodiagnostic study. In addition, magnetic resonance imaging showed a paralabral cyst in the right acetabulum which extended to the pelvic wall. The patient underwent conservative treatment without surgical procedure. The pain was decreased after 1 month of conservative therapy. The pain was decreased at the 1-month follow-up. Follow-up electromyography showed polyphasic motor unit potentials in adductor magnus and adductor longus muscles. Based on the experience of this case, an acetabular paralabral cyst should be considered as one of the rare causes of obturator neuropathy.
PMCID: PMC4092188  PMID: 25024971
Acetabulum; Synovial cyst; Obturator nerve
23.  Paraplegia due to Acute Aortic Coarctation and Occlusion 
Coarctation and occlusion of the aorta is a rare condition that typically presents with hypertension or cardiac failure. However, neuropathy or myelopathy may be the presenting features of the condition when an intraspinal subarachnoid hemorrhage has compressed the spinal cord causing ischemia. We report two cases of middle-aged males who developed acute non-traumatic paraplegia. Undiagnosed congenital abnormalities, such as aortic coarctation and occlusion, should be considered for patients presenting with nontraumatic paraplegia in the absence of other identifiable causes. Our cases suggest that spinal cord ischemia resulting from acute spinal subarachnoid hemorrhage and can cause paraplegia, and that clinicians must carefully examine patients presenting with nontraumatic paraplegia because misdiagnosis can delay initiation of the appropriate treatment.
PMCID: PMC4024816  PMID: 24851152
Paraplegia; Aortic coarctation; Aortic occlusion; Spinal cord ischemia
24.  Changes of bone metabolism based on the different interventions with exercise type or additional intake material in ovariectomized rats 
This study is aimed at providing clear guidance on treatment and prevention of osteoporosis by comparing and analyzing some well-known methods out of drug and exercise therapies.
For this purpose, eight-week experiments (drug therapy and exercise therapy) were carried out by using rats whose menopause was induced by the removal of an ovary. In the treatment of the drug therapy, the effects of soy protein, one of the well-known alendronate and estrogen replacement therapy, were compared and analyzed. In the treatment of the exercise therapy, endurance exercise using a treadmill and resistance exercise through climbing a special cage were compared and analyzed. Based on these results, this study will be able to suggest the most appropriate way to deal with osteoporosis which requires long-term treatment. Sixty eight-week-old Sprague-Dawley female rats had a week to adapt to the new environment. After that, they were randomly divided into four groups (Sham-Sedentary; SS, ovariectomized-control; OC, ovariectomized-soy protein; OS: ovariectomized-alendronate; OA, ovariectomized-endurance exercise; OE, ovariectomized-resistance exercise; OR) before having an operation for the removal of an ovary. After surgery, the rats convalesced for a week. Alendronate (0.4mg / kg of body weight) and isoflavones (200g / 1 kg of feed) were given to two groups respectively for eight weeks. The rats in the other two groups performed resistance exercise (climbing) and endurance exercise (20 m/min; 60min/day) five days a week for eight weeks.
Ovariectomy increased the body weight and body fat like menopause did. Soy protein and alendronate intake for eight weeks had no effect on body weight but reduced the body fat increased by ovariectomy to the level of the SS group. The menopause induced by ovariectomy did not affect total bone density and bone mass as well as bone density in specific areas of the body. Soy protein and alendronate intake for eight weeks did not significantly affect them either. However, the eight-week treatment with soy protein and alendronate significantly reduced the level of osteocalcin in blood. Resistance exercise more noticeably increased body weight and bone mass than running on the low-intensity treadmill but serum osteocalcin levels were notably increased in both cases.
These results show that soy protein which is natural produce and low-intensity, regular endurance exercise also have an effect on the treatment and prevention of osteoporosis caused by menopause.
PMCID: PMC4241939  PMID: 25566446
osteoporosis; soy protein; alendronate; endurance exercise; resistance exercise
25.  Self dsDNA induces IL-1β production from human monocytes by activating NLRP3 inflammasome in the presence of anti-dsDNA antibodies 
The pathogenic hallmark of systemic lupus erythematosus (SLE or lupus) is the autoimmune response against self nuclear antigens, including dsDNA. The increased expression of the pro-inflammatory cytokine IL-1β has been found in the cutaneous lesion and peripheral blood mononuclear cells from lupus patients, suggesting a potential involvement of this cytokine in the pathogenesis of lupus. IL-1β is produced primarily by innate immune cells like monocytes and can promote Th17 cell response, which is increased in lupus. IL-1β production requires cleaving pro-IL-β into IL-1β by the caspase-1-associated multiprotein complex called inflammasomes. Here we show that self dsDNA induces IL-1β production from human monocytes dependently of serum or purified IgG containing anti-dsDNA antibodies by activating the NLRP3 inflammasome. Reactive oxygen species (ROS) and K+ efflux were involved in this activation. Knocking down the NLRP3 or inhibiting caspase-1, ROS and K+ efflux decreased IL-1β production. Supernatants from monocytes treated with a combination of self dsDNA and anti-dsDNA antibody-positive serum promoted IL-17 production from CD4+ T cells in an IL-1β dependent manner. These findings provide new insights in lupus pathogenesis by demonstrating that self dsDNA together with its autoantibodies induces IL-1β production from human monocytes by activating the NLRP3 inflammasome through inducing ROS synthesis and K+ efflux, leading to the increased Th17 cell response.
PMCID: PMC3563755  PMID: 23315075

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