MLN51 and GM-CSF involvement in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unclear etiology. This study was conducted to identify critical factors involved in the synovial hyperplasia in RA pathology. We applied cDNA microarray analysis to profile the gene expressions of RA fibroblast-like synoviocytes (FLSs) from patients with RA. We found that the MLN51 (metastatic lymph node 51) gene, identified in breast cancer, is remarkably upregulated in the hyperactive RA FLSs. However, growth-retarded RA FLSs passaged in vitro expressed small quantities of MLN51. MLN51 expression was significantly enhanced in the FLSs when the growth-retarded FLSs were treated with granulocyte – macrophage colony-stimulating factor (GM-CSF) or synovial fluid (SF). Anti-GM-CSF neutralizing antibody blocked the MLN51 expression even though the FLSs were cultured in the presence of SF. In contrast, GM-CSF in SFs existed at a significant level in the patients with RA (n = 6), in comparison with the other inflammatory cytokines, IL-1β and TNF-α. Most RA FLSs at passage 10 or more recovered from their growth retardation when cultured in the presence of SF. The SF-mediated growth recovery was markedly impaired by anti-GM-CSF antibody. Growth-retarded RA FLSs recovered their proliferative capacity after treatment with GM-CSF in a dose-dependent manner. However, MLN51 knock-down by siRNA completely blocked the GM-CSF/SF-mediated proliferation of RA FLSs. Taken together, our results imply that MLN51, induced by GM-CSF, is important in the proliferation of RA FLSs in the pathogenesis of RA

New Heteroleptic Cobalt Precursors for Deposition of Cobalt-Based Thin Films

A new series of heteroleptic complexes of cobalt were synthesized using aminoalkoxide and ??-diketonate ligands. The complexes, [Co(dmamp)(acac)]2 (3), [Co(dmamp)(tfac)]2 (4), [Co(dmamp)(hfac)]2 (5), [Co(dmamp)(tmhd)]2 (6), and [Co(dmamb)(tmhd)]2 (7), were prepared by two-step substitution reactions and studied using Fourier transform infrared spectroscopy, mass spectrometry, elemental analysis, and thermogravimetric analysis (TGA). Complexes 3-7 displayed dimeric molecular structures for all of the complexes with cobalt metal centers interconnected by ??2-O bonding by the alkoxy oxygen atom. TGA and a thermal study of the complexes displayed high volatilities and stabilities for complexes 6 and 7, with sublimation temperatures of 120 ??C/0.5 Torr and 130 ??C/0.5 Torr, respectively

Is it possible to reduce intra-hospital transport time for computed tomography evaluation in critically ill cases using the Easy Tube Arrange Device?

Objective Patients are often transported within the hospital, especially in cases of critical illness for which computed tomography (CT) is performed. Since increased transport time increases the risks of complications, reducing transport time is important for patient safety. This study aimed to evaluate the ability of our newly invented device, the Easy Tube Arrange Device (ETAD), to reduce transport time for CT evaluation in cases of critical illness. Methods This prospective randomized control study included 60 volunteers. Each participant arranged five or six intravenous fluid lines, monitoring lines (noninvasive blood pressure, electrocardiography, central venous pressure, arterial catheter), and therapeutic equipment (O2 supply device, Foley catheter) on a Resusci Anne mannequin. We measured transport time for the CT evaluation by using conventional and ETAD method. Results The median transport time for CT evaluation was 488.50 seconds (95% confidence interval [CI], 462.75 to 514.75) and, 503.50 seconds (95% CI, 489.50 to 526.75) with 5 and 6 fluid lines using the conventional method and 364.50 seconds (95% CI, 335.00 to 388.75), and 363.50 seconds (95% CI, 331.75 to 377.75) with ETAD (all P<0.001). The time differences were 131.50 (95% CI, 89.25 to 174.50) and 148.00 (95% CI, 116.00 to 177.75) (all P<0.001). Conclusion The transport time for CT evaluation was reduced using the ETAD, which would be expected to reduce the complications that may occur during transport in cases of critical illness

Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

Background/AimsSpontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection.MethodsNinety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels.ResultsOnly one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥5.1×107 IU/mL and ALT ≥5×ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure.ConclusionsSpontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection

Effect of Nebulized Bovine Surfactant for Experimental Otitis Media with Effusion

ObjectivesIn this study, we evaluated the efficacy of nebulized bovine pulmonary surfactant on experimentally induced otitis media with effusion (OME) in guinea pigs.MethodsTwenty guinea pigs were divided into three groups. Four untreated animals served as normal controls. Experimental OME was established in both ears of the remaining 16 animals by a transbullar injection of 10 µL of Pseudomonas aeruginosa lipopolysaccharide in saline. Thereafter, the guinea pigs received nebulized phosphate buffered saline (n=8) or nebulized bovine pulmonary surfactant (n=8). Nebulization was given daily for 7 days. On day 8, all the animals' passive opening pressure (POP) of the Eustachian tube was measured and histopathological observations of the bulla were made by light microscopy.ResultsNebulized bovine pulmonary surfactant significantly reduced the POP compared to that of saline nebulization. The bovine pulmonary surfactant improved the tubal patency and produced less histopathologcally-evident edematous bullar mucosa.ConclusionNebulization of bovine pulmonary surfactant plays an important role in treating otitis media with effusion in guinea pigs. Our results suggest that the chosen nebulized bovine pulmonary surfactant can be of good clinical benefit for treating OME in the future

Spontaneous Closure of Iatrogenic Coronary Artery Fistula to Left Ventricle After Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy

Cases of iatrogenic coronary artery fistulas draining into the left ventricle after surgical myectomy for hypertrophic obstructive cardiomyopathy have been published as sporadic reports. However, its management scheme and prognosis are not clear because of the low incidence. A 46-yr-old woman was hospitalized for evaluation of chest pain and shortness of breath for 3 months. Transthoracic echocardiographic examination showed typical hypertrophic obstructive cardiomyopathy with a peak pressure gradient of 71 mmHg across the left ventricular outflow tract. The patient underwent surgical septal myectomy. Postoperative color Doppler imaging revealed a diastolic blood flow from the interventricular septal myocardium to the left ventricular cavity, i.e. iatrogenic coronary artery fistula to the left ventricle. Ten days later, the fistula closed spontaneously which was diagnosed by transthoracic echocardiography and confirmed by coronary angiography

A Validation Study of the Korean Version of SPAN

Purpose: The SPAN, which is acronym standing for its four components: Startle, Physiological arousal, Anger, and Numbness, is a short post-traumatic stress disorder (PTSD) screening scale. This study sought to develop and validate a Korean version of the SPAN (SPAN-K). Materials and Methods: Ninety-three PTSD patients (PTSD group), 73 patients with non-psychotic psychiatric disorders (psychiatric control group), and 88 healthy participants (normal control group) were recruited for this study. Participants completed a variety of psychiatric assessments including the SPAN-K, the Davidson Trauma Scale (DTS), the Clinician-Administered PTSD Scale (CAPS), and the State-Trait Anxiety Inventory (STAI). Results: Cronbach&#39;s alpha and test-retest reliability values for the SPAN-K were both 0.80. Mean SPAN-K scores were 10.06 for the PTSD group, 4.94 for the psychiatric control group, and 1.42 for the normal control group. With respect to concurrent validity, correlation coefficients were 0.87 for SPAN-K vs. CAPS total scores (p&lt;0.001) and 0.86 for SPAN-K vs. DTS scores (p&lt;0.001). Additionally, correlation coefficients were 0.31 and 0.42 for SPAN-K vs. STAI-S and STAI-T, respectively. Receiver operating characteristic analysis of SPAN-K showed good diagnostic accuracy with an area under the curve (AUC) of 0.87. The SPAN-K showed the highest efficiency at a cutoff score of 7, with a sensitivity of 0.83, a specificity of 0.81, positive predictive value (PPV) of 0.88, and negative predictive value (NPV) of 0.73. Conclusion: These results suggest that the SPAN-K had good psychometric properties and may be a useful instrument for rapid screening of PTSD patients.This study was supported by a grant of the Korean Academy of Anxiety Disorders, Korean Neuropsychiatric Association, and Korean Research Foundation (2006-2005152), Republic of Korea

Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery

Background Despite the effectiveness of glucagon-like peptide-1 agonist (GLP-1A) in the treatment of diabetes, its large molecular weight and high hydrophilicity result in poor cellular permeability, thus limiting its oral bioavailability. To address this, we developed a chimeric GLP-1A that targets transporter-mediated endocytosis to enhance cellular permeability to GLP-1A by utilizing the transporters available in the intestine, particularly the apical sodium-dependent bile acid transporter (ASBT). Methods In silico molecular docking and molecular dynamics simulations were used to investigate the binding interactions of mono-, bis-, and tetra-deoxycholic acid (DOCA) (monoDOCA, bisDOCA, and tetraDOCA) with ASBT. After synthesizing the chimeric GLP-1A-conjugated oligomeric DOCAs (mD-G1A, bD-G1A, and tD-G1A) using a maleimide reaction, in vitro cellular permeability and insulinotropic effects were assessed. Furthermore, in vivo oral absorption in rats and hypoglycemic effect on diabetic db/db mice model were evaluated. Results In silico results showed that tetraDOCA had the lowest interaction energy, indicating high binding affinity to ASBT. Insulinotropic effects of GLP-1A-conjugated oligomeric DOCAs were not different from those of GLP-1A-Cys or exenatide. Moreover, bD-G1A and tD-G1A exhibited improved in vitro Caco-2 cellular permeability and showed higher in vivo bioavailability (7.58% and 8.63%) after oral administration. Regarding hypoglycemic effects on db/db mice, tD-G1A (50 μg/kg) lowered the glucose level more than bD-G1A (50 μg/kg) compared with the control (35.5% vs. 26.4%). Conclusion GLP-1A was conjugated with oligomeric DOCAs, and the resulting chimeric compound showed the potential not only for glucagon-like peptide-1 receptor agonist activity but also for oral delivery. These findings suggest that oligomeric DOCAs can be used as effective carriers for oral delivery of GLP-1A, offering a promising solution for enhancing its oral bioavailability and improving diabetes treatment.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (grant nos. 2020R1A2C1102831, 2022R1A5A8033794, 2022R1A4A3034038). This study was also supported by Regional Innovation Strategy (RIS) through the NRF funded by the Ministry of Education (MOE) (2021RIS-001