Objective of present study was to prepare and characterize self-nanoemulsifying drug delivery system (SNEDDS) of lutein and to evaluate its effect on bioavailability of warfarin. The SNEDDS was prepared using an oil, a surfactant, and co-surfactants with optimal composition based on pseudo-ternary phase diagram. Effect of the SNEDDS on the bioavailability of warfarin was performed using Sprague Dawley rats. Lutein was successfully formulated as SNEDDS for immediate self-emulsification and dissolution by using combination of Peceol as oil, Labrasol as surfactant, and Transcutol-HP or Lutrol-E400 as co-surfactant. Almost complete dissolution was achieved after 15 min while lutein was not detectable from the lutein powder or intra-capsule content of a commercial formulation. SNEDDS formulation of lutein affected bioavailability of warfarin, showing about 10% increase in Cmax and AUC of the drug in rats while lutein as non-SNEDDS did not alter these parameters. Although exact mechanism is not yet elucidated, it appears that surfactant and co-surfactant used for SNEDDS formulation caused disturbance in the anatomy of small intestinal microvilli, leading to permeability change of the mucosal membrane. Based on this finding, it is suggested that drugs with narrow therapeutic range such as warfarin be administered with caution to avoid undesirable drug interaction due to large amount of surfactants contained in SNEDDS.
Animals ; Area Under Curve ; Biological Availability* ; Drug Delivery Systems* ; Drug Interactions ; Lutein* ; Membranes ; Microvilli ; Permeability ; Rats ; Rats, Sprague-Dawley ; Surface-Active Agents ; Warfarin*

Interleukin-6(IL-6) stimulate osteoclast differentiation. 17beta-estradiol, 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) and interleukin-1beta inhibit or stimulate osteoclast differentiation by decreasing or increasing the synthesis of interleukin-6(IL-6) from stromal/osteoblastic cells, respectively. Periodontal ligament(PDL) cells reside between the alveolar bone and the cementum and have osteoblastic characteristics. To estimate the effect of 17beta-estradiol and 1,25(OH)2D3 on IL-6 production of PDL cells, PDL cells were treated with 17beta-estradiol or 1,25-(OH)2D3 in the absence or the presence of IL-1beta. The concentration of IL-6 produced form PDL cells was determined by enzym linked immunosorbent assay(ELISA). In unstimulated PDL cells, we detected constitutive production of IL-6 at 1st and 2nd day. IL-1beta increased IL-6 synthesis at 1st day and 2nd day. 17beta-estradiol had no significant effect on the secretion of this cytokine, either constitutively or after stimulation with IL-1beta(0.05 ng/ml). 1,25-(OH)2D3(10(-8)M) decreased not only constitutive IL-6 production but also IL-1beta-induced IL-6 production at 2nd day. These results suggest that 1,25-(OH)2D3 may control IL-1beta-induced osteoclast differentiation by decreasing IL-1beta-induced IL-6 secretion of PDL cells.
Calcitriol* ; Dental Cementum ; Interleukin-1beta ; Interleukin-6* ; Osteoblasts ; Osteoclasts ; Periodontal Ligament*

Immunoadjuvant activities of the extract (KM-110) from Korean mistletoe ( Viscum album coloratum) on the induction of humoral and cellular responses against Keyhole limpet hemocyanim (KLH) as an antigen and allogenic tumor cells were examined. When mice were immunized subcataneously (s.c.) with KLH admixed with KM-110, more than 1000-times higher antibody titers to KLH than those immunized with KLH alone was observed. KM-110 induced high level of KLH- specific IgG1, IgG2a and IgG2b antibodies. In an in vitro analysis of lymphocytes proliferation to KLH on week 4, the splenocytes of mice treated with KLH and KM- 110 exhibited significantly higher proliferating activity than those treated with KLH alone. In addition, the culture supernatnats obtained from the splenocytes of mice treated with both KLH and KM-110 showed high level of IL-2 and IL-4. In the test of cellular immune responses, KM-110 enhanced the DTH reaction to KLH in mice. Furthemore, cytotoxic T-lymphocyte (CTL) activity using an allogenic CTL induction model where C57BL/6 (H-2b) mice were injected with allogenic P815 (H-2d) mastocytoma cells admixed with or without KM-110, mice treated with P815 cells and KM-110 showed higher cytatoxic activity against allogenic tumor cells than those treated without KM-110. This results suggest that KM-110 may possess adjuvant activities to potentially enhance humoral as well as cellular immune responses against antigens.
Animals ; Antibodies ; B-Lymphocytes ; Immunity, Cellular* ; Immunoglobulin G ; Interleukin-2 ; Interleukin-4 ; Lymphocytes ; Mastocytoma ; Mice ; Mistletoe* ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic ; Viscum album* ; Viscum*

OBJECTIVE: This study aimed to provide efficacy and safety information on the use of erenumab for prevention of episodic and chronic migraines. METHODS: The keywords “Erenumab and migraine” were used to search the PubMed database to then compile efficacy and safety data for erenumab. Data from relevant Phase 2 and Phase 3 clinical trials were analyzed, using RevMan for statistical analysis. RESULTS: Three clinical trials (one Phase 2 and two Phase 3 studies) were retrieved. All three trials used the same primary endpoint (change from baseline in monthly migraine days (CBMD)) to evaluate efficacy and safety of erenumab use for prevention of episodic and chronic migraines. Subcutaneous doses of erenumab (70 or 140 mg) were administered monthly in each trial, for 3 months (Studies 2, and 3) or 6 months (Study 1). The mean differences in CBMD in the 70 mg and 140 mg erenumab arms were −1.36 and −1.98, respectively, compared to that in the placebo arm. Some adverse events, such as nasopharyngitis and upper respiratory tract infection, were reported, but no differences in safety between erenumab and placebo were found to be significant. CONCLUSIONS: Erenumab showed superior efficacy in prevention of migraines compared to placebo. However, additional information regarding the long-term safety of erenumab should be collected. Therefore, post-marketing surveillance for adverse events is needed.
Arm ; Migraine Disorders ; Nasopharyngitis ; Respiratory Tract Infections

A brief episode of ischemia and reperfusion termed 'ischemic preconditioning' has been established as rendering muscle tolerance to damage during a subsequent prolonged ischemia. The effects of ischemic preconditioning in the cardiac muscle are related to the stimulation of adenosine A1 receptor and the opening of KATP channel. The effect and mechanisms of ischemic preconditioning in the skeletal muscle are not known clearly. The superoxide radical injures the skeletal muscle during the ischemia and reperfusion. There are two types of SOD, which metabolizes the superoxide radicals to H2O2 and O2, in the cell. One of them is Cu, Zn-SOD in the cytoplasm and the other is Mn-SOD in the mitochondria. The activities of SOD are increased against the formation of superoxide radical during the reperfusion. The author performed the present study to investigate the effect and the mechanisms of ischemic preconditioning by measuring the expression of SOD mRNA on timely reperfused ischemic muscles. The healthy Sprague-Dawley rats weighing from 300 g to 350 g were used as experimental animals. Under pentobarbital (50 mg/kg) anesthesia, lower abdominal incision was done and left common iliac artery was occluded by vascular clamp for 2 hours. Rectus femoris muscles were obtained respectively at 3, 6, 12, 24 and 72 hours after reperfusion. The ischemic preconditioning group underwent three episodes of 5 minute occlusion and 5 minute reperfusion of common iliac artery followed by 2 hours of ischemia and timely reperfusion. Adenosine (50 microgram/kg) or pinacidil (1 mg/kg) was administered intravenously before ischemia. 8-cyclopentyl-1, 3-dipropylxanthine (15 mg/kg) or glibenclamide (0.5 mg/kg) was administered intravenously before ischemic preconditioning. Paraffin sections with 4 micrometer thickness in all groups were obtained. The expression of Cu, Zn- and Mn-SOD mRNA was observed by use of in situ hybridization. The results obtained were as follows. 1. The expression of SOD mRNA was seen only in small muscle fibers of the rectus femoris muscle of the rat. 2. Weak expressions of Cu, Zn- and Mn-SOD mRNA were observed in the normal control rat. 3. After 2 hours of ischemia, moderate expression of Cu, Zn-SOD mRNA was observed until 72 hours of reperfusion. Weak or moderate expression of Mn-SOD mRNA at 3 hours and 6 hours of reperfusion, weak or trace expression at 12 hours of reperfusion, moderate expression at 24 hours of reperfusion and weak or moderate expression at 72 hours of reperfusion were observed. 4. After ischemic preconditioning, moderate expressions of Cu, Zn-SOD mRNA were seen in the groups of 3, 6, 12 and 24 hours of reperfusion. Moderate expressions of Mn-SOD mRNA were seen in the group of 0, 3, 6 and 12 hours of reperfusion and strong expression was seen in the group of 24 hours of reperfusion after ischemic preconditioning. 5. After 2 hours of ischemia with ischemic preconditoining, moderate expressions of Cu, Zn-SOD mRNA were seen in the groups of 0, 3, 6, 12, 24 hours of reperfusion. Moderate expressions of Mn-SOD mRNA were observed in the groups of 0, 3, 6, and 12 hours of reperfusion and moderate or strong expression was seen in the group of 24 hours of reperfusion. 6. After 2 hours of ischemia with the pretreatment of adenosine, moderate expressions of Cu, Zn-SOD mRNA were seen in the group of 0, 3, 6, 12 and 24 hours of reperfusion. Moderate expression of Mn-SOD mRNA in the groups and 3 hours of reperfusion, strong expression in the group of 6 and 12 hours of reperfusion and moderate expression in the group of 24 hours of reperfusion were seen. 7. After 2 hours of ischemia with the pretreatment of pinacidil, moderate expressions of Cu, Zn-SOD mRNA were seen in the groups of 0, 3, 6 and 12 hours of reperfusion and those of Mn-SOD mRNA were seen in the groups of 3, 6, 12 and 24 hours of reperfusion. 8. After 2 hours of ischemia with ischemic preconditioning and the pretreatment of 8-cyclopentyl-1, 3- dipropylxanthine, moderate expression of Cu, Zn-SOD mRNA were observed in the groups of 0, 3, 6, and 12 hours of reperfusion and those of Mn-SOD were seen in the groups of 6, 12 and 72 hours of reperfusion. 9. After 2 hours of ischemia with ischemic preconditioning and the pretreatment of glibenclamide, moderate expressions of Cu, Zn- and Mn-SOD mRNA were seen in all groups of reperfusion. Consequently, these results suggest that the expression of Cu, Zn and Mn-SOD mRNA increases during 2 hours ischemia and reperfusion with or without ischemic preconditioning. The effects of ischemic preconditioning are closely related to the stimulation of adenosine A1 receptor and KATP channel.
Adenosine* ; Anesthesia ; Animals ; Cytoplasm ; Glyburide ; Iliac Artery ; In Situ Hybridization ; Ischemia* ; Ischemic Preconditioning* ; Mitochondria ; Muscle, Skeletal ; Muscles ; Myocardium ; Paraffin ; Pentobarbital ; Pinacidil* ; Quadriceps Muscle* ; Rats* ; Rats, Sprague-Dawley ; Receptor, Adenosine A1 ; Reperfusion* ; RNA, Messenger* ; Superoxide Dismutase* ; Superoxides

PURPOSE: The purpose of this study was to establish optimal imaging acquisition conditions for the GE Advance(TM) PET imaging system by performing the acceptance tests designed by National Electrical Manufacturers Association (NEMA) protocol and General Electric Medical Systems (GEMS) test procedures. MATERIALS AND METHODS: Performance tests were carried out with 18FDG radioactivity source and phantoms by using a standard acquisition mode. Transaxial resolution and scatter fraction tests were performed with a line source and axial resolution with a point source, respectively. A cylindrical phantom made of polymethylmethacrylate (PMMA) was used to measure sensitivity, count rate losses and randoms, uniformity correction, and attenuation inserts were added to measure remaining tests. The test results were acquired in a diagnostic acquisition mode and analyzed mainly on high sensitivity mode. RESULTS: Transaxial resolution and axial resolution were measured as average of 4.65 mm and 3.98 mm at 0 cm, and 6.02 mm and 6.71 mm at 20 cm on high sensitivity mode, respectively. Average scatter fraction was 9.87%, and sensitivity was 225.8 kcps/micronCi/cc of trues. Activity at 50% deadtime was 4.6 Ci/cc, and the error of count rate correction at that activity was from 1.49% to 3.83%. Average nonuniformity for total slice was 8.37%. The accuracy of scatter correction was -0.95%. The accuracies of attenuation correction were 5.68% for air, 0.04% for water and -6.51% for polytetrafluoroethylene (PTFE). CONCLUSION: The results satisfied most acceptance criteria, indicating that the GE AdvanceTM PET system can be optimally used for clinical applications.
Electrons* ; Fluorodeoxyglucose F18 ; Polymethyl Methacrylate ; Polytetrafluoroethylene ; Positron-Emission Tomography* ; Radioactivity ; Water

PURPOSE: As the National Health Insurance Service (NHIS) began to cover home oxygen therapy (HOT) services from 2006, it is expected that the new services have contributed to overall positive outcome of patients with chronic obstructive pulmonary disease (COPD). We examined whether the usage of HOT has helped slow down the progression of COPD. METHODS: We examined hospital claim data (N=10,798) of COPD inpatients who were treated in 2007~2012. We performed chi2 tests to analyze the differences in the changes to respiratory impairment grades. Multiple logistic regression analysis was used to identify factors that are associated with the use of HOT. Finally, a generalized linear mixed model was used to examine association between the HOT treatment and changes to respiratory impairment grades. RESULTS: A total of 2,490 patients had grade 1 respiratory impairment, and patients with grades 2 or 3 totaled 8,308. The OR for use of HOT was lower in grade 3 patients than others (OR: 0.33, 95% CI: 0.30~0.37). The maintenance/mitigation in all grades, those who used HOT had a higher OR than non-users (OR: 1.41, 95% CI: 1.23~1.61). CONCLUSION: HOT was effective in maintaining or mitigating the respiratory impairment in COPD patients.
Home Care Services ; Humans ; Inpatients ; Logistic Models ; Lung Diseases, Obstructive* ; National Health Programs ; Oxygen Inhalation Therapy ; Oxygen* ; Pulmonary Disease, Chronic Obstructive ; Respiratory Mechanics

A total of 32 cases of cervical myelography via lateral c1-2 puncture using water-soluble metrizamide was evaluated. Twenty seven cases were suspected to have herniated cervical disc and five cases, spinal cord tumor. Patients were placed in prone position with head and neck slightly extended on the radiolucent operating table. Puncture was performed using 22-guage spinal puncture needle placed at the junction of the middle and posterior one-third of the bony spinal canal and 4-6mm inferior to the arch of atlas on lateral projection. The needle was positioned posterior to the spinal cord into the subarachnoid space. The author could obtain more clear images with less amount of contrast medium than doses used in conventional cervical myelography via lumbar route. The were relatively few adverse reactions and no considerable complications have been encountered with a new cervical water-soluble metrizamide myelography via C1-2 puncture.
Head ; Humans ; Metrizamide* ; Myelography* ; Neck ; Needles ; Operating Tables ; Prone Position ; Punctures* ; Spinal Canal ; Spinal Cord ; Spinal Cord Neoplasms ; Spinal Puncture ; Subarachnoid Space

Treponema lecithinolyticum is known to be associated with rapidly progressive periodontitis. The full-length gene encoding the major surface protein MspTL of this organism was cloned and expressed by using the expression vector pQE30. Recombinant Msp TL (rMsp TL) protein was purified and functionally characterized. Msp TL was one of several T. lecithinolyticum surface proteins that bound to cultured human gingival fibroblasts (HGFs). As well, it strongly induced IL-6 production by HGFs. These observations suggest that MspTL contributes to pathogenesis of periodontitis by adhesion to host cells and by induction of the proinflammatory cytokine IL-6.
Clone Cells ; Fibroblasts ; Humans ; Interleukin-6 ; Membrane Proteins* ; Membranes* ; Periodontitis ; Treponema*

Herein, we report a case of nasal natural killer T-cell lymphoma (NKTL) with intraocular involvement. A 57-year-old woman was referred due to a three-day history of photophobia and diplopia in the left eye. One-month previously, she was diagnosed with nasal NKTL of the right nasal cavity. Ophthalmic examination revealed conjunctival injection and ptosis. The left pupil was fully dilated and non-reactive to light. Ocular motion was restricted on left-upper gaze. Five days later, anterior uveitis developed and persisted despite topical steroid treatment. An orbital magnetic resonance imaging was without specific findings, however, ophthalmoplegia, vitreous opacity, and an iris mass were observed. A diagnostic anterior chamber aspiration was performed. Aqueous humor aspiration revealed 35% morphologically atypical lymphocytes. After an intravitreal triamcinolone injection, radiotherapy and chemotherapy were administered; this resolved the uveitis and iris mass. When refractory uveitis or orbital pseudotumor occurs in patients with nasal NKTL, ocular and orbital involvement of the NKTL should be considered.
Diagnosis, Differential ; Eye Neoplasms/diagnosis/*secondary/therapy ; Fatal Outcome ; Female ; Humans ; Lymphoma, T-Cell/*pathology ; Magnetic Resonance Imaging ; Middle Aged ; Natural Killer T-Cells/*pathology ; Nose Neoplasms/*pathology