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

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

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*

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

Alveolar bone destruction is a characteristic of periodontal disease. Treponema denticola are found in significantly increased numbers in the sites affected with periodontal disease. In order to clarify the role of T. denticola in destruction of alveolar bone in periodontal disease, this study was undertaken to determine the effect of sonicated extract of T. denticola on osteoclast differentiation in co-culture system of mouse bone marrow cells and calvaria cells. The ability of osteoclast formation was estimated by counting the number of tartrate resistant acid phosphatase(TRAP) positive cells. Sonicated extract of this bacteria stimulated osteoclast formation in a dose dependent manner(p<0.05). Indomathacin, an inhibitor of prostaglandin synthesis, decreased osteoclast formation induced by sonicated extract of this bacteria(p<0.05). Extract-induced osteoclast formation was decreased, when sonicated extract of bacteria was heated(p<0.05). These findings suggest that T. denticola induces osteoclast differentiation, and protein component of this bacteria and PGE2 may play an important role in this process.
Mice ; Animals

The term myotubular myopathy (MTM) implies a maturational arrest of fetal muscle during the myotubular stage of development at 8-15 weeks of gestation. Characteristic muscle histopathology consists of small hypotrophic muscle fibers with centrally placed nuclei and a surrounding clear area devoid of myofibrils. X-linked recessive inheritance is the most common trait. Autosomal recessive and autosomal dominant forms are less frequently reported. The clinical diagnostic criterion for X-linked MTM has relied on a positive family history and the demonstration of the presence of characteristic biopsy findings from affected male subjects. Additional features may include perinatal onset, severe hypotonia, respiratory failure, dysphagia, thin ribs, contractures of the hips or knees, puffy eyelids and ophthalmoplegia. The prognosis is often fatal, and most patients die within the first year of life from respiratory failure. The authors report a case of presumed X-linked MTM with severe hypotonia, muscle weakness and respiratory failure at birth.
Biopsy ; Contracture ; Deglutition Disorders ; Eyelids ; Hip ; Humans ; Knee ; Male ; Muscle Hypotonia ; Myofibrils ; Myopathies, Structural, Congenital* ; Ophthalmoplegia ; Parturition ; Pregnancy ; Prognosis ; Respiratory Insufficiency ; Ribs ; Wills