Anti-diabetic effects of Protaetia brevitarsis in pancreatic islets and a murine diabetic model.

OBJECTIVE: In this study, the antidiabetic efficacy of Protaetia brevitarsis in alloxan-treated pancreatic islets and db/db mice was investigated. P. brevitarsis was tested for alloxan-mediated cytotoxicity and nitric oxide production in mice pancreatic islets. MATERIALS AND METHODS: The anti-diabetic effect of P. brevitarsis was also evaluated in db/db mice after 4 weeks of administration. Biochemical analysis, oral glucose tolerance test (OGTT), and pancreatic histological analysis were performed. RESULTS: P. brevitarsis displayed hypoglycemic activity in alloxan-treated mice pancreatic islets. Our results showed that P. brevitarsis protects pancreatic islets from cytotoxicity. Moreover, daily oral supplementation with P. brevitarsis for 4 weeks reduced plasma glucose levels without affecting body weight and food intake, elevated glucose tolerance in OGTT, improved blood lipid parameters, inhibited fat accumulation, and restored islet structure of db/db mice. CONCLUSIONS: The present study provided evidence for the anti­diabetic effect of P. brevitarsis in alloxan-treated pancreatic islets and db/db mice. These results suggest that P. brevitarsis may be used as an adjunctive anti-diabetic agent or as a functional food.

Nickel, chromium and methyl methacrylate monomer release from orthopaedic functional appliances.

AIM: This study was purposed to evaluate release of nickel and chromium ions and methyl methacrylate (MMA) monomers from functional appliances and their possible health effects. MATERIALS AND METHODS: Study design: Twin-block appliances and Bionators were immersed in artificial saliva and kept in a thermal incubator. Control group was established as artificial saliva without appliances. Artificial saliva was analysed after 7 days, 30 days and 90 days. Inductively coupled plasma mass spectrometry and gas chromatography-mass spectrometry was used for detection of nickel and chromium ions and MMA monomers. MTT assays and cytokine array were performed. STATISTICS: One way ANOVA with Tukey test and Dunnett's T3 for post-hoc analysis was used for evaluation of time-dependent changes and independent t-test was used for evaluation of MTT assay results. RESULTS: The results revealed that metal ions and MMA monomers are released from the appliances. Metal ion detection pattern was irregular and could not be analysed. Twin-block group showed significantly larger amount of MMA release. MTT assay revealed statistically significant but minimally reduced cellular activity on Bionator and twin-block groups compared to control groups. Cytokine array showed no or less inflammatory cytokine release on Bionator and twin-block groups. CONCLUSION: MMA monomer release was confirmed but the cytotoxic effect of functional appliance material release is minimal or negligible. General toxicity of the functional appliance from the MMA monomer release is likely to be minimal or negligible.

Submandibular soft tissue changes after mandibular set-back surgery in skeletal Class III patients.

PURPOSE: To investigate the submandibular soft tissue changes related to the hard tissue changes after mandibular set-back surgery in skeletal Class III patients. METHODS: The subjects were adults with skeletal Class III malocclusion who underwent orthognathic surgery including mandibular set-back between June 2007 and January 2011 at Kyung Hee University Dental Hospital at Gandong. Standardized lateral cephalograms that were taken before and 6 to 12 months after surgery were collected. Sixty samples were selected. Each lateral cephalograms was traced and lines, angles and areas associated with submandibular soft tissues were measured and analyzed statistically. RESULTS: Anteroposterior submandibular soft tissue length was reduced with reduction of mandibular body length. FH to mandibular plane angle was decreased and FH to submandibular line angle was increased. A gender difference was found in soft tissue changes. Males showed altered vertical soft tissue thickness and submandibular tissue area reduction after surgery. Several hard tissue changes were correlated with soft tissue changes and through multiple regression models with stepwise selection method, several regression equation models to predict soft tissue changes related to hard tissue changes were made. CONCLUSION: After orthognathic surgery including mandibular set-back, the submandibular soft tissue profile changes. Equations to predict submandibular soft tissue changes after mandibular set-back surgery were developed.

Bioinformatic analysis of responsive genes in two-dimension and three-dimension cultured human periodontal ligament cells subjected to compressive stress.

BACKGROUND AND OBJECTIVE: Analyzing responses of human periodontal ligament cells to mechanical stress and mechanotransduction is important for understanding periodontal tissue physiology and remodeling. It has been shown that the cellular response to mechanical stress can vary according to the type and duration of force and to extracellular attachment conditions. This study investigated the gene-expression profile of human periodontal ligament cells cultured in two-dimension (2D) and three-dimension (3D) conditions after application of compressive stress for 2 and 48 h. MATERIAL AND METHODS: Human primary periodontal ligament cells were obtained from premolars extracted for orthodontic purposes. Cells were cultured in a conventional 2D culture dish or in 3D collagen gel and compressive stress was applied for 2 and 48 h. Control cells were cultured under identical conditions but without the application of compressive stress. After the application of compressive stress, total RNA was extracted and a cDNA microarray was performed. Microarray data were analyzed using statistical methods, including david and gene set enrichment analysis to identify significant signaling pathways. Real-time PCR was performed for five mRNAs in order to confirm the cDNA microarray results. RESULTS: The cDNA microarray analysis revealed that after application of compressive stress for 2 h, 191 and 553 genes showed changes in their expression levels in 2D and 3D cultured cells, respectively. After application of compressive stress for 48 h, 280 and 519 genes showed changes in their expression levels in 2D and 3D cultured cells, respectively. Euclidean clustering method was used to demonstrate the gene-expression kinetics. CONCLUSION: Analysis of the results showed that several signaling pathways, including the MAPK pathway and the focal adhesion kinase pathway are relevant to the compressive force-induced cellular response. 2D and 3D cultured cells showed significantly different gene-expression profiles, suggesting that cellular attachment to extracellular matrix influences cellular responses to mechanical stresses.

Soybean extract showed modulation of retinoic acid-related gene expression of skin and photo-protective effects in keratinocytes.

Soy extracts are well known as medicinal and nutritional ingredients, and exhibit benefits towards human skin including depigmenting or anti-ageing effects. Despite the wrinkle decreasing effects of retinoids on skin as an anti-ageing ingredient, retinoid application can causes photo-sensitive responses such as skin irritation. Thus, their daytime usage is not recommended. The aim of this study is the investigation into the activities of soybean extract as an anti-ageing ingredient and their comparison to retinoids in this respect. Soybean extract decreased the relative ratio of MMP-1/TIMP-1 mRNA to the same degree as retinoic acid in normal human fibroblasts. It also affected mRNA levels of HAS2 and CRABP2 in normal human keratinocytes. Furthermore, we investigated its effect on mRNA expression of histidase, an enzyme that converts histidine into urocanic acid, the main UV light absorption factor of the stratum corneum. Unlike the complete inhibition of histidase exhibited by the mRNA expression of retinoic acid, the effect of soybean extract on histidase gene expression was weaker in normal human keratinocytes. Also, soybean extract pretreatment inhibited UVB-induced cyclobutane pyrimidine dimer formation dose-dependently in normal human keratinocytes. In this study, we found that soybean extract modulated retinoic acid-related genes and showed photo-protective effects. Our findings suggest that soybean extract could be an anti-ageing ingredient that can be safely used under the sunlight.

Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells.

Recently, Sirtuin 1 (SIRT1) has been implicated in the molecular control of ageing and immune response. Although the remodelling of periodontal ligament (PDL) in response to mechanical stress (MS) is mediated by several host factors, including cytokines and chemokines, the transmission of mechanical stimuli into specific cellular activity is still not understood fully. This study aimed to investigate the effects of MS, particularly cyclic strain, on immune response genes, as well as SIRT1 and its signal transduction pathways, in human PDL cells. MS up-regulated the expression of SIRT1 and immune response genes encoding cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-1ß], chemokines [IL-8, monocyte cheoattractant protein (CCL)-20], defensins [human ß-defensin (hBD)-2, hBD-3] and Toll-like receptors (TLR-2 and TLR-4) in a force- and time-dependent manner. The SIRT1 inducers resveratrol and isonicotinamide attenuated MS-induced cytokine and chemokine expression, but enhanced the expression of defensins and TLRs. Blockade of SIRT1 activity by the SIRT1 inhibitors sirtinol and nicotinamide and down-regulation of SIRT1 expression by SIRT1 siRNA reduced the stimulatory effects of MS on defensins and TLRs, but increased its effects on cytokines and chemokines. MS induced activation of protein kinase B (Akt), protein kinase C (PKC), nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Treatment with the anti-oxidants N-acetylcysteine and glutathione inhibited MS-induced reactive oxygen species production and expression of cytokines, chemokines, defensins and TLRs. These results suggest that MS activates human PDL cells to express immune/defence genes encoding cytokines, chemokines, defensins and TLRs via a SIRT1 pathway.

Patient expectations of total knee replacement and their association with sociodemographic factors and functional status.

We aimed to document the pre-operative expectations in Korean patients undergoing total knee replacement using an established survey form and to determine whether expectations were influenced by sociodemographic factors or pre-operative functional status. Expectations regarding 17 items in the Knee Replacement Expectation Survey form were investigated in 454 patients scheduled for total knee replacement. The levels and distribution patterns of summated expectation and of five expectation categories (relief from pain, baseline activity, high flexion activity, social activity and psychological well-being) constructed from the 17 items were assessed. Univariate analyses and multivariate logistic regression were performed to examine the associations of expectations with the sociodemographic factors and the functional status. The top three expectations were relief from pain, restoration of walking ability, and psychological well-being. Of the five expectation categories, relief from pain was ranked the highest, followed by psychological well-being, restoration of baseline activity, ability to perform high flexion activities and ability to participate in social activities. An age of < 65 years, being employed, a high Western Ontario and McMaster Universities osteoarthritis index function score and a low Short-form 36 social score were found to be significantly associated with higher overall expectations.

FAK pathway regulates PGE2 production in compressed periodontal ligament cells.

This study examined the role of focal adhesion kinase (FAK) as a mechanoreceptor in human periodontal ligament (hPDL) cells. hPDL cells were obtained from premolars extracted for orthodontic purposes. Mechanical stress was applied in a compressive manner (2 g/cm(2)) for various time durations (0.5, 2, 6, 24, 48 hrs) with or without a knockdown treatment for FAK. Compressive stimulation increased the level of phosphorylated FAK and prostaglandin E(2) production. The FAK-knockdown cells showed significantly lower prostaglandin E(2) levels than the control cells. Furthermore, compressive stress up-regulated cyclo-oxygenase-2 mRNA, whereas there were no changes observed in the FAK-knockdown cells. These results suggest that FAK regulates the production of prostaglandin E(2) via the transcriptional regulation of COX-2 mRNA in compressive stimulated PDL cells. The FAK-integrin complex plays a role in mechanoreception and mechanotransduction in hPDL cells.

The relationship of the medially-offset stem of the tibial component to the medial tibial cortex in total knee replacements in Korean patients.

We examined the placement of the stem in relation to the medial tibial cortex when using total knee replacements (TKRs) with medially-offset tibial stems in Korean patients. Measurements were performed on the pre- and post-operative radiographs of 246 osteoarthritic knees replaced between January 2005 and May 2006 using the Genesis II or E-motion TKR with a medially-offset stem. Pre-operatively, we measured the distance between the mechanical axis and that of the tibial shaft and post-operatively, that between the midline of the tibial stem and the axis of the shaft. Knees were identified in which there was radiological contact between the tip of the stem and the medial tibial cortex. The mechanical axis was located medial to the axis of the shaft in 203 knees (82.5%). Post-operatively, the midline of the tibial stem was located medial to the tibial shaft axis in 196 knees (79.7%). In 16 knees (6.5%) there was radiological contact between the tibial stem or cement mantle and the medial tibial cortex. Our study has shown that the medially-offset stem in the tibial component may not be a good option for knees undergoing replacement for advanced osteoarthritis in some Korean patients.

Correlation of maximum flexion with clinical outcome after total knee replacement in Asian patients.

This study aimed to determine the correlation between the amount of maximum flexion and the clinical outcome in 207 Koreans (333 knees) undergoing total knee replacement. The association of maximum flexion with clinical outcome was evaluated one year postoperatively using three scoring systems; the American Knee Society score, Western Ontario McMaster Universities Osteoarthritis index and the Short Form-36. The mean maximum flexion decreased post-operatively at 12 months from 140.1 degrees (60 degrees to 160 degrees ) to 133.0 degrees (105 degrees to 150 degrees ). Only the social function score of the Short Form-36 correlated significantly with maximum flexion (correlation coefficient = 0.180, p = 0.039). In comparative analyses of subgroups divided by a maximum flexion of 120 degrees , we found no significant differences in any parameters except the social function score of the Short Form-36 (41.9 vs 47.3, p = 0.031). Knees with a maximum flexion of more than 135 degrees had a better functional Western Ontario McMasters Universities Osteoarthritis index score than knees with maximum flexion of 135 degrees or less (17.5 vs 14.3, p = 0.031). We found only weak correlation between the postoperative maximum flexion and the clinical parameters for pain relief, function and quality of life, even in Korean patients. Efforts to increase post-operative maximum flexion should be exercised with caution until concerns relating to high-flexion activities are sufficiently resolved.

Age-related change in serum concentrations of testosterone in middle-aged Korean men.

The objective of this study was to determine whether testosterone and sex hormone binding globulin (SHBG) levels are different between healthy men and men with chronic illness, and to evaluate the age-related changes of testosterone and SHBG in healthy men in Korea. enrollment took place between January 2000 and December 2001 at Pundang CHA General Hospital in Korea. All men who came for male climacteric and geriatric health screening examinations were eligible. Of the 762 men recruited, 136 men had at least one present or previous medical illness and 626 men were healthy. Higher serum concentrations of total testosterone (5.31 +/- 1.88 ng/ml vs. 4.96 +/- 1.43 ng/ml; p < 0.05), free androgen index (16.60 +/- 7.36 vs. 14.57 +/- 5.55; p < 0.01) and calculated bioavailable testosterone (8.88 +/- 3.52 nmol/l vs. 7.91 +/- 2.52 nmol/l; p < 0.01) were demonstrated in the healthy compared with the disease group. Total testosterone declined at a rate of 0.2% per year, SHBG increased by 1.74% per year, calculated bioavailable testosterone declined by 0.8% per year, and free androgen index declined by 1.15% per year in healthy subjects aged between 40 and 70. The above results seem to be consistent with previous Western studies, showing higher concentrations of testosterone in healthy men, that decline with increasing age.

Blast-wave-sphere interaction using a laser-produced plasma: an experiment motivated by supernova 1987A.

We present x-ray shadowgraphs from a high Mach number ( approximately 20) laboratory environment that simulate outward flowing ejecta matter from supernovae that interact with ambient cloud matter. Using a laser-plastic foil interaction, we generate a "complex" blast wave (a supersonic flow containing forward and reverse shock waves and a contact discontinuity between them) that interacts with a high-density (100 times ambient) sphere. The experimental results, including vorticity localization, compare favorably with two-dimensional axisymmetric hydrodynamic simulations.

Effect of 0.1% dexamethasone on epithelial healing in experimental corneal alkali wounds: morphological changes during the repair process.

BACKGROUND: The effect of 0.1% dexamethasone on epithelial healing was evaluated in corneal alkali wounds. METHODS: Epithelial wounds were induced by a 60-s application of a round filter paper (5.5 mm) soaked in 1 N NaOH onto the central cornea of the rabbit. Animals were treated with 0.1% dexamethasone 4 times each day for 8 weeks in one subgroup and only for the 1st week in the other subgroup. The control eyes were treated with a balanced salt solution. The repair processes of epithelium and its basement membrane were evaluated morphologically and morphometrically. RESULTS: Treatment with 0.1% dexamethasone was found to retard the repair process of epithelial healing compared with the control eyes. Morphologically, the basement membrane in the control cornea was damaged focally at 2 days, maximally disrupted at 4 weeks, and regained the normal integrity at 8 weeks after the initial alkali damage. In 0.1% dexamethasone-treated corneas, regardless of the application period, the basement membrane structure was visible up to 4 weeks but disappeared at 8 weeks after the initial alkali wounds. The eyes treated with 0.1% dexamethasone for 8 weeks showed an intense infiltration of inflammatory cells in the superficial stroma 4 weeks after treatment. CONCLUSION: A topical application of 0.1% dexamethasone retarded the corneal epithelial healing. The cornea treated with 0.1% dexamethasone only for the 1st week maintained a well-preserved basement membrane for as long as 4 weeks after initial damage without enhancement of the inflammatory cell infiltration. However, further study is needed to prevent late disintegration of the basement membrane.

Prolonged release of tegafur from S/O/W multiple emulsion.

To develop a prolonged and sustained release preparation, we prepared an albumin microsphere-in-oil-in-water emulsion (S/O/W) and examined sustained release from it in comparison with other control preparations such as water-in-oil (W/O) emulsions and microspheres in vitro and in vivo, respectively. Tegafur was used as a model drug. A microsphere-in-oil emulsion was prepared by adding albumin microspheres to soybean oil containing 20% Span 80. To prepare an S/O/W emulsion, the microsphere-in-oil emulsion was added into an aqueous solution of hydroxypropyl methylcellulose containing Pluronic F68. The mean particle size of the albumin microspheres was 3 microns, and the ratio of entrapment of tegafur into albumin microspheres was about 25%. In an in vitro release test, the t75 of the S/O/W emulsion was fourfold greater and in an in vivo release test the mean residence time of tegafur from the S/O/W emulsion was more than twofold that from a W/O emulsion or microsphere system. The mean residence time of 5-fluorouracil (5-FU) from an S/O/W emulsion was also greater than with other dosage forms. These results suggest the possible usefulness of an S/O/W emulsion for the sustained and prolonged release of tegafur.

Systemic effects of tissue plasminogen activator-associated fibrinolysis and its relation to thrombin generation in orthotopic liver transplantation.

Orthotopic liver transplantation is frequently associated with hyperfibrinolysis, the origin and clinical relevance of which is largely unknown. In 20 orthotopic liver transplantations, we studied the occurrence and systemic effects of hyperfibrinolysis. Severe fibrinolysis was defined to be present when the euglobulin-clot lysis time and the whole-blood-clot lysis time, as measured by thrombelastography, were shorter than 60 and 90 min, respectively, at some time during the operation. Based on these criteria, 7 patients had minimal fibrinolysis (group I), and 13 patients had severe fibrinolysis (group II). In group II a gradual increase of tissue-type plasminogen activator (t-PA) activity was seen during the anhepatic stage, followed by an "explosive" increase immediately after graft reperfusion (P = 0.0004, compared with group I), and a reduction of plasminogen activator inhibitor (PAI) activity. Plasma degradation products of fibrinogen and fibrin increased parallel to t-PA activity, and levels were significantly higher at 45 min after graft reperfusion in group II compared with group I (P less than 0.04). Thrombin-antithrombin III complexes showed an identical steady increase in both groups, indicating that increased t-PA activity was not related to thrombin formation. A combination of increased endothelial release and reduced hepatic clearance may have caused the increased t-PA activity. The t-PA-associated destruction of fibrinogen and fibrin after graft reperfusion is consistent with the clinical signs of severe oozing often seen in this period. These observations may have important clinical implications for the treatment of bleeding in patients undergoing orthotopic liver transplantation.

Intraoperative blood transfusions in highly alloimmunized patients undergoing orthotopic liver transplantation.

Intraoperative blood requirements were analyzed in patients undergoing primary orthotopic liver transplantation and divided into two groups on the basis of panel reactive antibody of pretransplant serum measured by lymphocytotoxicity testing. One group of highly sensitized patients (n = 25) had PRA values of over 70% and the second group of patients (n = 26) had 0% PRA values and were considered nonsensitized. During the transplant procedure, the 70% PRA group received considerably greater quantities of blood products than the 0% PRA group--namely, red blood cells: 21.1 +/- 3.7 vs. 9.8 +/- 0.8 units (P = 0.002), and platelets: 17.7 +/- 3.2 vs. 7.5 +/- 1.5 units (P = 0.003). Similar differences were observed for fresh frozen plasma and cryoprecipitate. Despite the larger infusion of platelets, the blood platelet counts in the 70% PRA group were lower postoperatively than preoperatively. Twenty patients in the 70% PRA group received platelet transfusions, and their mean platelet count dropped from 95,050 +/- 11,537 preoperatively to 67,750 +/- 8,228 postoperatively (P = 0.028). In contrast, nearly identical preoperative (84,058 +/- 17,297) and postoperative (85,647 +/- 12,445) platelet counts were observed in the 17 0% PRA patients who were transfused intraoperatively with platelets. Prothrombin time, activated partial thromboplastin time, and fibrinogen levels showed no significant differences between both groups. These data demonstrate that lymphocytotoxic antibody screening of liver transplant candidates is useful in identifying patients with increased risk of bleeding problems and who will require large quantities of blood during the transplant operation.