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1.  In Vitro Study of Antiadipogenic Profile of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in Human Orbital Preadiopocytes 
Abstract
Purpose
To investigate the effect of prostaglandin F2α (PGF2α), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome.
Methods
Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2α, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ), and CCAAT-enhancer-binding protein α (C/EBPα) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR.
Results
Our results showed that PGF2α and topical prostaglandin analogs down-regulated the expression of PPARγ and C/EBPα, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis.
Conclusion
Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2α analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma.
doi:10.1089/jop.2011.0160
PMCID: PMC3315164  PMID: 22107041
2.  Extremely Elevated International Normalized Ratio of Warfarin in a Patient with CYP2C9*1/*3 and Thyrotoxicosis 
Journal of Korean Medical Science  2014;29(9):1317-1319.
A 73-yr-old Korean man with permanent atrial fibrillation visited outpatient clinic with severely increased International Normalized Ratio (INR) values after taking a usual starting dosage of warfarin to prevent thromboembolism. We found out later from his blood tests that he had hyperthyroidism at the time of treatment initiation. His genetic analysis showed CYP2C9*1/*3 and VKORC1+1173TT genotypes. We suspect that both hyperthyroidism and genetic variant would have contributed to his extremely increased INR at the beginning of warfarin therapy. From this case, we learned that pharmacogenetic and thyroid function test might be useful when deciding the starting dosage of warfarin in patients with atrial fibrillation.
Graphical Abstract
doi:10.3346/jkms.2014.29.9.1317
PMCID: PMC4168188  PMID: 25246753
Warfarin; International Normalized Ratio; Thyrotoxicosis; Genotype
3.  Mycobacterium abscessus Lung Disease in a Patient with Kartagener Syndrome 
Primary ciliary dyskinesia (PCD) is characterized by the congenital impairment of mucociliary clearance. When accompanied by situs inversus, chronic sinusitis and bronchiectasis, PCD is known as Kartagener syndrome. The main consequence of impaired ciliary function is a reduced mucus clearance from the lungs, and susceptibility to chronic respiratory infections due to opportunistic pathogens, including nontuberculous mycobacteria (NTM). There has been no report of NTM lung disease combined with Kartagener syndrome in Korea. Here, we report an adult patient with Kartagener syndrome complicated with Mycobacterium abscessus lung disease. A 37-year-old female presented to our hospital with chronic cough and sputum. She was ultimately diagnosed with M. abscessus lung disease and Kartagener syndrome. M. abscessus was repeatedly isolated from sputum specimens collected from the patient, despite prolonged antibiotic treatment. The patient's condition improved and negative sputum culture conversion was achieved after sequential bilateral pulmonary resection.
doi:10.4046/trd.2014.77.3.136
PMCID: PMC4192312  PMID: 25309609
Kartagener Syndrome; Primary Ciliary Dyskinesia; Bronchiectasis; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous
4.  Silicone Stent Placement for Primary Tracheal Amyloidosis Accompanied by Cartilage Destruction 
Primary tracheal amyloidosis (PTA) can lead to airway obstructions, and patients with severe PTA should undergo bronchoscopic interventions in order to maintain airway patency. Focal airway involvements with amyloidosis can only be treated with mechanical dilatation. However, the PTA with diffused airway involvements and concomitant cartilage destructions requires stent placement. Limited information regarding the usefulness of silicone stents in patients with PTA has been released. Therefore, we report a case of diffused PTA with tracheomalacia causing severe cartilage destruction, which is being successfully managed with bronchoscopic interventions and silicone stent placements.
doi:10.4046/trd.2014.76.6.292
PMCID: PMC4092162  PMID: 25024724
Amyloidosis; Airway Obstruction; Bronchoscopy; Stents
5.  Epirubicin, Cisplatin, 5-FU combination chemotherapy in sorafenib-refractory metastatic hepatocellular carcinoma 
AIM: To evaluate the clinical efficacy and safety of epirubicin, cisplatin, and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma (HCC).
METHODS: From April 2009 to June 2012, 31 patients who were diagnosed with metastatic and progressive HCC after sorafenib treatment were retrospectively reviewed. Patients were treated with the combination of epirubicin (50 mg/m2 IV; day 1), cisplatin (60 mg/m2 IV; day 1), and 5-FU (1000 mg/m2 IV; day 1-3) [Epirubicin, cisplatin, 5-FU combination (ECF)], repeated every 4 wk.
RESULTS: The overall response rate was 12.9%. Patients who responded to ECF chemotherapy showed a longer overall survival (OS) and time to progression (TTP) relative to those in the non-responder group (OS: 20.4 mo vs 4.9 mo, P < 0.001, TTP: 9.4 mo vs 2.2 mo, P < 0.001). Patients with a stable primary liver mass also exhibited a longer OS and TTP relative to those with progressive disease (OS: 13.4 mo vs 5.3 mo, P = 0.003; TTP: 9.4 mo vs 2.3 mo, P = 0.003). The most common hematologic toxicity was thrombocytopenia (87.2%), and the incidence of grade 3-4 neutropenia was 53.9%. Age older than 60, a stable primary mass, and a good response to chemotherapy were prognostic factors for OS and TTP.
CONCLUSION: This combination cytotoxic chemotherapy can serve as another treatment option after sorafenib failure for the subset of patients with advanced metastatic HCC.
doi:10.3748/wjg.v20.i1.235
PMCID: PMC3886014  PMID: 24415877
Hepatocellular carcinoma; Sorafenib; Epirubicin; Cisplatin; 5-FU
6.  Comparison of High-resolution Anorectal Manometry With Water-perfused Anorectal Manometry 
Background/Aims
To date, high-resolution manometry has been used mainly in the study of esophageal motility disorders and has been shown to provide more physiological information than conventional manometry, and is easier to interpret. This study aimed to evaluate the usefulness of high-resolution anorectal manometry (HRARM) compared to water-perfused anorectal manometry.
Methods
Patients who complained of chronic constipation with/without fecal incontinence underwent both water-perfused anorectal manometry and HRARM in a random order on the same day. Resting and squeezing pressures of the anal sphincter, attempted defecation, rectoanal inhibitory reflex, rectoanal contractile reflex, Rao’s type of dyssynergia during attempted defecation, anal canal length, defecation dynamic parameters and measurement times for each method were analyzed.
Results
Of 14 patients, 7 were female, and the median age was 59 years (range 35–77). Indications for manometry were constipation (n = 8) and constipation with fecal incontinence (n = 6). Resting and squeezing pressures showed that the 2 methods were strongly correlated (resting pressure: r = 0.746, P = 0.002; squeezing pressure: r = 0.921, P < 0.001). In attempted defection, one equivocal case with water-perfused anorectal manometry was diagnosed type I pelvic floor dyssynergia with HRARM providing detailed pressure changes in internal and external anal spincters, and puborectalis muscle which improved assessment of anorectal disorders. The measurement time for HRARM was significantly shorter than that for water-perfused anorectal manometry (11.3 vs 23.0 minutes, P < 0.001).
Conclusions
Both water-perfused anorectal manometry and HRARM are well tolerated and reliable methods of evaluating defecation disorders of pelvic floor dysfunction. HRARM is likely to provide better physiological information and to require a shorter measurement time compared to water-perfused anorectal manometry.
doi:10.5056/jnm14025
PMCID: PMC4288094  PMID: 25537672
Constipation; Defecation; Fecal incontinence; Manometry; High-resolution manometry
7.  Evaluation of anatomical considerations in the posterior maxillae for sinus augmentation 
The edentulous posterior maxilla is considered a clinical challenge during dental implant treatment for many dental practitioners. This is because its insufficient bone quality, deficient alveolar ridge, spiny ridges, undercuts, and sinus pneumatization are often encountered after tooth loss. To overcome these problems, several approaches have been developed and are currently used, including sinus augmentation and bone augmentation. Today, two main procedures of sinus floor elevation for dental implant placement are in use: a two-stage technique using the lateral window approach, and a one-stage technique using a lateral or a crestal approach. In this study, we deal with the anatomic relations of the structures of the maxillary sinus during sinus augmentation. These anatomical findings can help in complications and potential injuries of the maxillary sinus procedures. It can be suggested that pre-operative evaluation is helpful for diagnosis and treatment planning and minimizing complication during the surgery.
doi:10.12998/wjcc.v2.i11.663
PMCID: PMC4233423  PMID: 25405192
Anatomy; Intraoperative complications; Sinus floor augmentation
8.  Macular Hole Formation in Rhegmatogenous Retinal Detachment after Scleral Buckling 
Purpose
To describe early macular hole (MH) development in rhegmatogenous retinal detachment (RRD) after scleral buckling (SB) based on optical coherence tomography (OCT) findings.
Methods
The medical records and spectral domain OCT images of patients in whom MH developed after RRD repair were evaluated retrospectively.
Results
A postoperative MH was detected in five eyes that underwent SB during a 6-year period. All had fovea-off RRD without MH at the time of surgery. OCT showed partial loss of the inner retina with a preserved photoreceptor layer in early postoperative days. On average, 7 days (range,5 to 8 days) after surgery, outer retinal tissues disappeared, resulting in the full-thickness MH.
Conclusions
Serial OCT findings revealed that partial-thickness lamellar holes progressed to full-thickness MHs, which were formed by the degeneration of the outer retina in eyes with preceding loss of the glial cone in the fovea.
doi:10.3341/kjo.2014.28.5.364
PMCID: PMC4179112  PMID: 25276077
Retinal perforations; Rhegmatogenous retinal detachment; Scleral buckling
9.  Neural Changes Associated with Emotion Processing in Children Experiencing Peer Rejection: A Functional MRI Study 
Journal of Korean Medical Science  2014;29(9):1293-1300.
This study was performed to investigate differences between children who did and did not experience peer rejection in psychological state through surveys and in emotion processing during an interpersonal stress challenge task to reflect naturalistic interpersonal face-to-face relationships. A total of 20 right-handed children, 10 to 12 yr of age, completed self-rating questionnaires inquiring about peer rejection in school, depression, and anxiety. They then underwent an interpersonal stress challenge task simulating conditions of emotional stress, in reaction to positive, negative and neutral facial expression stimuli, using interpersonal feedbacks, and functional magnetic resonance imaging (FMRI) for an analysis of neural correlates during the task. Ten were the peer-rejection group, whereas the remainder were the control group. Based on the behavioral results, the peer-rejection group exhibited elevated levels of depression, state anxiety, trait anxiety and social anxiety as compared to the control group. The FMRI results revealed that the peer-rejection group exhibited greater and remarkably more extensive activation of brain regions encompassing the amygdala, orbitofrontal cortex and ventrolateral prefrontal cortex in response to negative feedback stimuli of emotional faces. The different brain reactivities characterizing emotion processing during interpersonal relationships may be present between children who do and do not experience peer rejection.
Graphical Abstract
doi:10.3346/jkms.2014.29.9.1293
PMCID: PMC4168185  PMID: 25246750
Peer Rejection; Child; Magnetic Resonance Imaging; Emotional Face Processing
10.  Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty 
Purpose
Long-acting gonadotropin-releasing hormone agonists (GnRHa) are commonly used to treat central precocious puberty (CPP) in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects.
Methods
This retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate) at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate.
Results
Six serious side effects (0.9%) were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621). Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE) in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy.
Conclusion
Sterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.
doi:10.6065/apem.2014.19.3.135
PMCID: PMC4208261  PMID: 25346917
Drug-related side effects and adverse reactions; Central precocious puberty; Leuprolide; Triptorelin
11.  The Ratio of Estimated Average Glucose to Fasting Plasma Glucose Level Is Superior to Glycated Albumin, Hemoglobin A1c, Fructosamine, and GA/A1c Ratio for Assessing β-Cell Function in Childhood Diabetes 
BioMed Research International  2014;2014:370790.
Objective. This study investigated the use of the estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to screen for β-cell function in pediatric diabetes. Methods. Glycated hemoglobin (HbA1c), glycated albumin (GA), fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c (GA/A1c ratio) was calculated, and the homeostasis model assessment of β-cell function (HOMA-β) was determined. Results. Median values of C-peptide, insulin, and HOMA-β levels were significantly higher in patients with an increased eAG/fPG ratio than in those with a decreased eAG/fPG ratio. C-peptide and HOMA-β levels were more closely correlated with the eAG/fPG ratio than with GA, HbA1c, the GA/A1c ratio, and fructosamine. In contrast, body mass index was significantly associated with GA, GA/A1c ratio, and fructosamine, but not with the eAG/fPG ratio and HbA1c levels. To test the diagnostic accuracies of the eAG/fPG ratio for identifying HOMA-β > 30.0% in patients with type 2 diabetes, the area under the ROC curve of the eAG/fPG ratio was significantly larger than that of the GA/A1c ratio [0.877 (95% CI, 0.780–0.942) versus 0.775 (95% CI, 0.664–0.865), P = 0.039]. Conclusions. A measurement of the eAG/fPG ratio may provide helpful information for assessing β-cell function in pediatric patients with diabetes.
doi:10.1155/2014/370790
PMCID: PMC4071783  PMID: 25013775
12.  Mosaic Turner syndrome associated with schizophrenia 
Turner syndrome is a sex-chromosome disorder; occurring in 1 in 2,500 female births. There are sporadic few case reports of concomitant Turner syndrome with schizophrenia worldwide. Most Turner females had a 45,X monosomy, whereas the majority of comorbidity between Turner syndrome and schizophrenia had a mosaic karyotype (45,X/46,XX). We present a case of a 21-year-old woman with Turner syndrome, mosaic karyotype (45,X/46,XX), showing mental retardation, hypothyroidism, and schizophrenia. HOPA gene within Xq13 is related to mental retardation, hypothyroidism, and schizophrenia. Our case may be a potential clue which supports the hypothesis for involvement of genes on X chromosome in development of schizophrenia. Further studies including comorbid cases reports are need in order to discern the cause of schizophrenia in patients having Turner syndrome.
doi:10.6065/apem.2014.19.1.42
PMCID: PMC4049549  PMID: 24926463
Turner syndrome; Schizophrenia; X chromosome; Mosaicism
13.  Conducting Polymer-Based Nanohybrid Transducers: A Potential Route to High Sensitivity and Selectivity Sensors 
Sensors (Basel, Switzerland)  2014;14(2):3604-3630.
The development of novel sensing materials provides good opportunities to realize previously unachievable sensor performance. In this review, conducting polymer-based nanohybrids are highlighted as innovative transducers for high-performance chemical and biological sensing devices. Synthetic strategies of the nanohybrids are categorized into four groups: (1) impregnation, followed by reduction; (2) concurrent redox reactions; (3) electrochemical deposition; (4) seeding approach. Nanocale hybridization of conducting polymers with inorganic components can lead to improved sorption, catalytic reaction and/or transport behavior of the material systems. The nanohybrids have thus been used to detect nerve agents, toxic gases, volatile organic compounds, glucose, dopamine, and DNA. Given further advances in nanohybrids synthesis, it is expected that sensor technology will also evolve, especially in terms of sensitivity and selectivity.
doi:10.3390/s140203604
PMCID: PMC3958277  PMID: 24561406
conducting polymer; nanohybrids; transducers; chemical sensors; biosensors
14.  H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation 
eLife  2013;2:e01503.
Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive. Furthermore, how these enzymes function on enhancers to regulate cell-type-specific gene expression is unclear. In this study, we identify MLL4 (KMT2D) as a major mammalian H3K4 mono- and di-methyltransferase with partial functional redundancy with MLL3 (KMT2C). Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of Mll4 markedly decreases H3K4me1/2, H3K27ac, Mediator and Polymerase II levels on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Together, these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation.
DOI: http://dx.doi.org/10.7554/eLife.01503.001
eLife digest
Almost every cell in a human body carries the same genes, but not every cell will express all of these genes as proteins. As different types of cells, such as brain, liver, fat or muscle cells, develop, they will express different genes; or they will express the same genes, but at different times and in different amounts. Enhancers are short stretches of DNA that boost the amount of protein that is produced when a gene is expressed, and they are particularly important for those genes that are expressed differently between cell types.
Enhancers bolster expression of a gene by interacting with the DNA nearby. Even genes separated from enhancers by a long stretches of DNA can benefit because the way that DNA is tightly packed inside the nucleus means that two distant sequences can actually end up close together. Proteins called transcription factors will bind to enhancers and recruit the cell’s protein ‘machinery’ required to express nearby genes. Enhancers can be identified by specific chemical marks associated with their DNA, but little is known about the enzymes that leave these marks in mammals. Moreover, it is not clear which genes are influenced by these marks.
Now, by examining fat cells and muscle cells as they mature, Lee et al. have found that an enzyme called MLL4 is responsible for adding chemical marks to enhancers in both humans and mice. Further, MLL4 is required both to allow cells to specialize into different cell types, and to boost the expression of genes that are specific to each type of mature cells. Since faulty MLL4 has been implicated in several cancers and developmental defects, the findings of Lee et al. may lead to a better understanding of these diseases.
DOI: http://dx.doi.org/10.7554/eLife.01503.002
doi:10.7554/eLife.01503
PMCID: PMC3869375  PMID: 24368734
enhancer chromatin modification; MLL4; H3K4me1; KMT2D; enhancer activation; H3K27ac; adipogenesis; myogenesis; cell differentiation; Human; Mouse
15.  Serum glycated albumin as a new glycemic marker in pediatric diabetes 
Purpose
Serum glycated albumin (GA) has been recently used as another glycemic marker that reflects shorter term glycemic control than glycated hemoglobin (HbA1c). Insulin secretory function and glycemic fluctuation might be correlated with the ratio of GA to HbA1c (GA/HbA1c) in diabetic adult patients. This study investigated the association of GA and GA/HbA1c ratio with the levels of fasting C-peptide, fasting plasma glucose in type 1 and type 2 pediatric diabetes.
Methods
Total 50 cases from 42 patients were included. The subjects were classified into type 1 diabetes mellitus (T1DM) (n=30) and type 2 diabetes mellitus (T2DM) (n=20) group. The associations among HbA1c, GA, and GA/HbA1c ratio were examined. The relationship between the three glycemic indices and fasting glucose, fasting C-peptide were analyzed.
Results
Mean values of GA, the GA/HbA1c ratio were significantly higher in T1DM than T2DM. GA (r=0.532, P=0.001), HbA1c (r=0.519, P=0.002) and the GA/HbA1c ratio (r=0.409, P=0.016) were correlated with the fasting plasma glucose. Fasting C-peptide level arranged 4.22±3.22 ng/mL in T2DM, which was significantly above the values in T1DM (0.26±0.49 ng/mL). There were no significant correlation between HbA1c and fasting C-peptide level. However, GA and the GA/HbA1c ratio exhibited inverse correlations with fasting C-peptide level (r=-0.214, P=0.002; r=-0.516, P<0.001).
Conclusion
GA seems to more accurately reflects fasting plasma glucose level than HbA1c. GA, GA/HbA1c ratio appear to reflect insulin secretory function.
doi:10.6065/apem.2013.18.4.208
PMCID: PMC4027086  PMID: 24904879
Diabetes mellitus; Glycosylated serum albumin; Glycosylated hemoglobin A; Child
16.  Variation in Serum Creatinine Level Is Correlated to Risk of Type 2 Diabetes 
Endocrinology and Metabolism  2013;28(3):207-213.
Background
Skeletal muscle is well established as a major target organ of insulin action, and is associated with the pathogenesis of type 2 diabetes. Therefore, we attempted to determine whether a variation in serum creatinine is related to the development of type 2 diabetes and other risk factors for diabetes.
Methods
A total of 2,676 nondiabetic subjects with stable and normal renal function (estimated glomerular filtration rate >60 mL/min/1.73 m2) were followed up for approximately 4.5 years. New onset diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated hemoglobin (HbA1c) ≥6.5%, or subjects taking antidiabetic agents. Variation of serum creatinine (ΔCre) was defined as a difference between follow-up and baseline creatinine. In subgroup analysis, body composition was examined by bioelectric impedance analysis method.
Results
A total of 106 subjects were diagnosed with new-onset diabetes during the follow-up period. Baseline serum creatinine was not different between the new-onset diabetes and no diabetes groups. Negative ΔCre (ΔCre <0) showed an association with increased risk of type 2 diabetes after adjusting for age, sex, body mass index, systolic blood pressure, FPG, HbA1c, triglyceride, high density lipoprotein cholesterol, and γ-glutamyl transpeptidase (odds ratio, 1.885; 95% confidence interval, 1.127 to 3.153). Serum creatinine level demonstrated positive correlation with muscle mass and negative correlation with percentage of body fat in body composition analysis.
Conclusion
Serum creatinine reflected body muscle mass and the decrease of serum creatinine might be regarded as a risk factor for type 2 diabetes.
doi:10.3803/EnM.2013.28.3.207
PMCID: PMC3811691  PMID: 24396680
Diabetes mellitus; Risk factors; Creatinine; Muscle mass
17.  Diagnostic value for extrahepatic metastases of hepatocellular carcinoma in positron emission tomography/computed tomography scan 
AIM: To evaluated the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan in diagnosis of hepatocellular carcinoma (HCC) and extrahepatic metastases.
METHODS: A total of 138 patients with HCC who had both conventional imaging modalities and 18F-FDG PET/CT scan done between November 2006 and March 2011 were enrolled. Diagnostic value of each imaging modality for detection of extrahepatic metastases was evaluated. Clinical factors and tumor characteristics including PET imaging were analyzed as indicative factors for metastases by univariate and multivariate methods.
RESULTS: The accuracy of chest CT was significantly superior compared with the accuracy of PET imaging for detecting lung metastases. The detection rate of metastatic pulmonary nodule ≥ 1 cm was 12/13 (92.3%), when < 1 cm was 2/10 (20%) in PET imaging. The accuracy of PET imaging was significantly superior compared with the accuracy of bone scan for detecting bone metastases. In multivariate analysis, increased tumor size (≥ 5 cm) (P = 0.042) and increased average standardized uptake value (SUV) uptake (P = 0.028) were predictive factors for extrahepatic metastases. Isometabolic HCC in PET imaging was inversely correlated in multivariate analysis (P = 0.035). According to the receiver operating characteristic curve, the optimal cutoff of average SUV to predict extrahepatic metastases was 3.4.
CONCLUSION: 18F-FDG PET/CT scan is invaluable for detection of lung metastases larger than 1 cm and bone metastases. Primary HCC having larger than 5 cm and increased average SUV uptake more than 3.4 should be considered for extrahepatic metastases.
doi:10.3748/wjg.v18.i23.2979
PMCID: PMC3380326  PMID: 22736922
18F-fluorodeoxyglucose positron emission tomography/computed tomography scan; Diagnosis; Hepatocellular carcinoma; Extrahepatic metastases
18.  Intravitreal triamcinolone acetonide for rebound phenomenon after high-dose intravenous steroid treatment in Vogt-Koyanagi-Harada disease 
The authors report two cases of rebound phenomenon treated with intravitreal triamcinolone acetonide in Vogt-Koyanagi-Harada (VKH) disease. Patients in the acute phase of VKH disease were treated with high-dose intravenous (IV) methylprednisolone (1 g/day) for 3 days. Serous retinal detachment decreased and visual acuity improved during IV steroid treatment. After switching to oral steroid treatment, choroiditis and visual acuity worsened. An injection of triamcinolone acetonide (4 mg) into the vitreous resulted in gradual resolution of subretinal fluid and improvement of visual acuity. Systemic steroids were tapered to discontinuation without a relapse of inflammation. Adjuvant intravitreal triamcinolone is useful in the management of the rebound phenomenon in VKH disease.
doi:10.2147/OPTH.S25477
PMCID: PMC3218169  PMID: 22125406
adjuvant intravitreal steroid; serous retinal detachment; visual acuity; choroiditis
19.  Combined Treatment of Photodynamic Therapy and Bevacizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration 
Purpose
To evaluate the outcome of a combined photodynamic therapy and intravitreal injection of bevacizumab in choroidal neovascularization secondary to age-related macular degeneration.
Methods
Photodynamic therapy (PDT) was administered to 28 eyes followed by 3 consecutive bevacizumab injections. Patients were followed-up for more than 12 months. At baseline, 1, 3, 6, and 12 months post PDT, visual acuity (VA) and central macular thickness were measured using optical coherence tomography.
Results
The mean VA was significantly improved from logarithm of the minimal angle of resolution 0.86 at baseline to 0.69 at 1 month (p = 0.011), 0.63 at 3 months (p = 0.003), 0.64 at 6 months (p = 0.004) and 0.60 at 12 months (p < 0.001). Central macular thickness decreased significantly from 328.3 µm at baseline to 230.0 µm at 6 months and 229.9 µm at 1 year (p < 0.001). Reinjection mean number was 0.4 for 6 months and 0.8 for 12 months. By 1 year, retreatment was performed in 10 eyes (36%).
Conclusions
PDT combined with three consecutive intraviteal bevacizumab injections was effective in improving VA and reducing central macular thickness.
doi:10.3341/kjo.2011.25.4.231
PMCID: PMC3149132  PMID: 21860568
Bevacizumab; Choroidal neovascularization; Macular degeneration; Photochemotherapy; Verteporfin
20.  Reorganization of Photoreceptor Layer on Optical Coherence Tomography Concurrent with Visual Improvement after Macular Hole Surgery 
To report three cases in which reorganization of the photoreceptor layer on optical coherence tomography (OCT) was concurrent with long-term visual recovery after macular hole surgery. Serial OCT scans of three eyes in which visual acuity continued to improve for 1 or more years after successful macular hole surgery were reviewed. Case 1. At postoperative four weeks, visual acuity was 20/100 with disorganized photoreceptor layer on OCT. The photoreceptor layer had been reorganized and visual acuity had improved to 20/25 by 1 year. Case 2. Two weeks after the operation, visual acuity was 20/125 and disorganization of the photoreceptor layer was noted. Visual acuity improved to 20/50 by four months. The photoreceptor layer had been partly reorganized and had appearance of a broken line. Visual acuity had improved to 20/40 and the photoreceptor layer had been reorganized further with a residual defect on OCT by 15 months. Case 3. Visual acuity at two weeks was 20/100. OCT revealed disorganization of the photoreceptor layer. Six months after the operation, the partly reorganized photoreceptor layer appeared as a broken line and visual acuity had reached 20/80. Visual acuity had improved further to 20/40 by 1 year, concurrent with improved organization of the photoreceptor layer. The reorganization of the photoreceptor layer plays a part in long-term improvement of visual acuity after macular hole surgery.
doi:10.3341/kjo.2008.22.2.137
PMCID: PMC2629936  PMID: 18612234
Macular hole; Optical coherence tomography; Photoreceptor reorganization
21.  Kdo hydroxylase is an inner core assembly enzyme in the Ko-containing lipopolysaccharide biosynthesis 
The lipopolysaccharide (LPS) isolated from certain important Gram-negative pathogens including a human pathogen Yersinia pestis and opportunistic pathogens Burkholderia mallei and Burkholderia pseudomallei contains D-glycero-D-talo-oct-2-ulosonic acid (Ko), an isosteric analog of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo). Kdo 3-hydroxylase (KdoO), a Fe2+/α-KG/O2 dependent dioxygenase from Burkholderia ambifaria and Yersinia pestis is responsible for Ko formation with Kdo2-lipid A as a substrate, but in which stage KdoO functions during the LPS biosynthesis has not been established. Here we purify KdoO from B. ambifaria (BaKdoO) to homogeneity for the first time and characterize its substrates. BaKdoO utilizes Kdo2-lipid IVA or Kdo2-lipid A as a substrate, but not Kdo-lipid IVA in vivo as well as in vitro and Kdo-(Hep)kdo-lipid A in vitro. These data suggest that KdoO is an inner core assembly enzyme that functions after the Kdo-transferase KdtA but before the heptosyl-transferase WaaC enzyme during the Ko-containing LPS biosynthesis.
doi:10.1016/j.bbrc.2014.08.153
PMCID: PMC4282518  PMID: 25204504
Ko formation; Kdo hydroxylase; LPS inner core assembly; Burkholderia LPS Fe2+/O2/α-KG dependent dioxygenase
22.  Oseltamivir (Tamiflu)-induced bilateral acute angle closure glaucoma and transient myopia 
Indian Journal of Ophthalmology  2014;62(12):1165-1167.
A 27-year-old woman developed bilateral acute angle closure glaucoma (AACG) and transient myopia after taking oseltamivir for four days. On the fourth day, she received systemic and topical intraocular pressure (IOP)-lowering agents, and IOP decreased in both eyes. However, her visual acuity was unchanged. A myopic shift of -5.25 D OD and -5.0 D OS was estimated to have occurred in the acute phase. A-scan ultrasonography and Pentacam showed markedly shallow anterior chambers and increased lens thickness. Ultrasound biomicroscopy revealed an annular ciliochoroidal effusion with forward displacement of the lens-iris diaphragm. Ciliochoroidal effusion and transient myopia were resolved after discontinuation of oseltamivir.
doi:10.4103/0301-4738.109531
PMCID: PMC4313501  PMID: 23571265
Acute angle closure glaucoma; ciliochoroidal effusion; oseltamivir; transient myopia
23.  Nox4-Mediated Cell Signaling Regulates Differentiation and Survival of Neural Crest Stem Cells 
Molecules and Cells  2014;37(12):907-911.
The function of reactive oxygen species (ROS) as second messengers in cell differentiation has been demonstrated only for a limited number of cell types. Here, we used a well-established protocol for BMP2-induced neuronal differentiation of neural crest stem cells (NCSCs) to examine the function of BMP2-induced ROS during the process. We first show that BMP2 indeed induces ROS generation in NCSCs and that blocking ROS generation by pretreatment of cells with diphenyleneiodonium (DPI) as NADPH oxidase (Nox) inhibitor inhibits neuronal differentiation. Among the ROS-generating Nox isozymes, only Nox4 was expressed at a detectable level in NCSCs. Nox4 appears to be critical for survival of NCSCs at least in vitro as down-regulation by RNA interference led to apoptotic response from NCSCs. Interestingly, development of neural crest-derived peripheral neural structures in Nox4−/− mouse appears to be grossly normal, although Nox4−/− embryos were born at a sub-Mendelian ratio and showed delayed over-all development. Specifically, cranial and dorsal root ganglia, derived from NCSCs, were clearly present in Nox4−/− embryo at embryonic days (E) 9.5 and 10.5. These results suggest that Nox4-mediated ROS generation likely plays important role in fate determination and differentiation of NCSCs, but other Nox isozymes play redundant function during embryogenesis.
doi:10.14348/molcells.2014.0244
PMCID: PMC4275708  PMID: 25410908
bone morphogenetic protein; neural crest stem cell; neuronal differentiation; Nox4; reactive oxygen species
24.  Fermentation with Aquilariae Lignum Enhances the Anti-Diabetic Activity of Green Tea in Type II Diabetic db/db Mouse 
Nutrients  2014;6(9):3536-3571.
The major components of tea may be significantly influenced according to the type of fermentation, and consequently the effects of different teas will differ. We examined whether green tea fermented with Aquilariae Lignum (fGT) shows a stronger anti-diabetic effect than unfermented green tea (GT) on mice with type 2 diabetes. To evaluate the anti-obesity effect of fGT, we assessed body weight, fecal excretion, serum leptin levels, exocrine pancreatic zymogen granule contents, and periovarian fat weight and adiponectin contents. Blood glucose levels, pancreatic weight, and numbers of pancreatic islet insulin- and glucagon-producing cells were determined to evaluate anti-hypoglycemic effects, while total cholesterol, triglyceride, and low- and high-density lipoprotein levels were determined to evaluate anti-hyperlipidemic effects. The antioxidant effect of fGT was detected by measuring malondialdehyde and glutathione contents and the activities of catalase and superoxide dismutase. fGT showed anti-obesity, anti-hypoglycemic, anti-hyperlipidemia, and antioxidant effects. Additionally, fGT exerted stronger anti-diabetic effects compared with GT. Collectively, these results suggested that fGT fermented with the appropriate amounts of Aquilariae Lignum (49:1) has a stronger effect compared with GT. Thus, fGT is a promising and potent new therapeutic agent for type 2 diabetes.
doi:10.3390/nu6093536
PMCID: PMC4179175  PMID: 25207824
BKS.Cg-+Leprdb/+Leprdb/OlaHsd (db/db) mice; obese; diabetes; fermented green tea with Aquilariae Lignum; synergistic
25.  A Case of Drug-Induced Interstitial Pneumonitis Caused by Valproic Acid for the Treatment of Seizure Disorders 
Valproic acid is one of the most common antiepileptic drugs used for the treatment of several seizure disorders. A 20-year-old man presented with a sudden decline of consciousness. He had a neurosurgery operation for intracranial and intraventricular hemorrhage. Following surgery, antiepileptic medication was administered to the patient in order to control his seizure events. On valproic acid treatment, he began to complain of fever and dyspnea. His symptoms persisted despite receiving empirical antibiotic treatment. All diagnostic tests for infectious causes were negative. A high-resolution computed tomography scan of the chest revealed predominantly dependent consolidation and ground-glass opacities in both lower lobes. The primary differential was drug associated with interstitial lung disease. Therefore, we discontinued valproic acid treatment and began methylprednisolone treatment. His symptoms and radiologic findings had significantly improved after receiving steroid therapy. We propose that clinicians should be made aware of the potential for valproic acid to induce lung injury.
doi:10.4046/trd.2014.77.3.145
PMCID: PMC4192314  PMID: 25309611
Valproic Acid; Lung Diseases, Interstitial; Drug Hypersensitivity

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