Visit-to-visit changes in fasting blood sugar and the risk for cardiovascular disease and mortality in the Korean population: a nationwide population-based cohort study.

OBJECTIVE: The importance of continuous monitoring of fasting blood sugar (FBS) levels of diabetic patients has been established. MATERIALS AND METHODS: An observational prospective study was conducted. Our analysis included 1,700,796 individuals from the nationwide South Korean National Health Insurance System cohort. FBS variability was measured by standard deviation (SD). RESULTS: Kaplan-Meier curves demonstrated elevated disease probability in the higher FBS fluctuation group compared with the lower FBS fluctuation group. After adjusting for confounding variables, Cox proportional hazards analysis showed that the hazard ratios of 411 individuals in the highest quartile of SD variation of FBS were 1.77 (95% confidence interval 1.37-2.28, p<0.001) compared with the lowest quartile of SD variation of FBS. The impact of FBS fluctuation on the risk of cardiovascular diseases (CVDs), cerebrovascular diseases, CVD mortality and all-cause mortality in the highest quartiles of diabetic and non-diabetic individuals was statistically significant. CONCLUSIONS: Visit-to-visit FBS variability has prognostic value for predicting micro- and macrovascular disease, cardiovascular mortality, and all-cause mortality.

Pilot study on the correlation between skin auto-fluorescence and serum antioxidant enzyme: skin auto-fluorescence is negatively associated with levels of malondialdehyde.

BACKGROUND/PURPOSE: Various methods have been used to objectively record skin changes. However, estimating the intrinsic and extrinsic aging of skin remains a challenge. Our objective was to study intrinsic skin aging with respect to patient age and extrinsic photo-aging of human dorsal (photo-exposed) and volar (photo-protected) forearm in vivo through skin auto-fluorescence (AF). We also examined the correlations between serum antioxidant enzyme, malondialdehyde(MDA), and skin AF. METHODS: 37 healthy volunteers were enrolled. We measured skin AF and its heterogeneity on the dorsal and volar forearms. We also examined serum concentration of catalase, superoxide dismutase, vitamin E, and MDA levels in every participant. RESULTS: In photo-protected areas, skin AF intensity in the 40 years or older group was significantly higher compared to the group less than 40 years-old. On the other hand, heterogeneity value was significantly higher in the less than 40 years-old group in photo-protected area. With respect to serum antioxidant enzyme and MDA level, only MDA level showed a negative correlation with skin AF intensity in photo-exposed area. CONCLUSION: We determined that skin AF intensity of the photo-protected area reflects intrinsic skin aging. In addition, degree of photo-aging could be indirectly inferred by skin AF of photo-exposed area and serum MDA level.

The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study.

UNLABELLED: A high level of circulating sphingosine-1-phosphate (S1P) is associated with a high incidence of osteoporotic fracture and a high rate of an insufficient response to bisphosphonate therapy. INTRODUCTION: Sphingosine-1-phosphate (S1P) is a significant regulator of bone metabolism. Recently, we found that a high plasma S1P level is associated with low bone mineral density (BMD), high levels of bone resorption markers (BRMs), and a high risk of prevalent vertebral fracture in postmenopausal women. We investigated the possibility that S1P is a predictor of incident fracture. METHODS: A total of 248 postmenopausal women participated in this longitudinal study and were followed up for a mean duration of 3.5 years (untreated [n = 76] or treated with bisphosphonate or hormone replacement therapy [n = 172]). The baseline plasma S1P level and prevalent and incident fracture occurrence were assessed. RESULTS: A high S1P level was significantly associated with a higher rate of prevalent fracture after adjusting for femoral neck (FN) BMD, BRM, and potential confounders (odds ratio = 2.05; 95 % confidence interval [CI] = 1.03-4.00). Incident fractures occurred more frequently in the highest S1P tertile (T3) than in the lower two tertiles (T1-2) after adjusting for confounders, including baseline FN BMD, prevalent fracture, antiosteoporotic medication, annualized changes in FN BMD, BRM, and potential confounders (hazard ratio = 5.52; 95 % CI = 1.04-56.54). Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1-2 (odds ratio = 4.43; 95 % CI = 1.02-21.25). CONCLUSIONS: The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.

Association between changes in body composition and risk of developing Type 2 diabetes in Koreans.

AIMS: To examine the effects of longitudinal changes in fat mass or lean body mass on risk of Type 2 diabetes in Korean adults. METHODS: Participants included 18 687 Korean adults (aged 20-79 years) who underwent routine medical check-ups in 2007-2008 and again in 2011-2012 with a mean (range) of 4.3 (3.0-5.7) years interval. Total fat, fat-free, and soft fat-free masses were determined using bioelectrical impedance. RESULTS: A total of 692 subjects (3.7%) developed Type 2 diabetes during follow-up. Those who developed diabetes had a greater increase in percent body fat (2.9 ± 3.0 vs 2.6 ± 3.2 percentage points, P = 0.043), as well as greater decreases in percent fat-free mass (-3.0 ± 3.3 vs -2.7 ± 3.3 percentage points, P = 0.008) and percent soft fat-free mass (-2.8 ± 3.1 vs -2.4 ± 3.1 percentage points, P = 0.003) compared with those who did not develop diabetes. In multiple logistic regression analysis, an increase in total fat mass of > 10% was associated with an increased odds ratio for diabetes (1.29, 1.05-1.60), and a decreased total fat mass was associated with lower odds ratio (0.75, 0.58-0.96). A loss of total fat-free mass of > 5% (odds ratio 1.08, 0.90-1.30) or an increase in total fat-free mass (odds ratio 0.96, 0.71-1.28) was not significantly associated with the risk of diabetes after adjustments for baseline waist circumference and glucose levels. CONCLUSIONS: These results show that changes in total body fat mass, but not lean body mass, are associated with development of Type 2 diabetes, independently of baseline measures of general or central obesity.

Higher serum uric acid as a protective factor against incident osteoporotic fractures in Korean men: a longitudinal study using the National Claim Registry.

UNLABELLED: In this large longitudinal study of 16,078 Korean men aged 50 years or older, we observed that baseline elevation of serum uric acid level significantly associated with a lower risk of incident fractures at osteoporosis-related sites during an average follow-up period of 3 years. INTRODUCTION: Male osteoporosis and related fractures are becoming recognized as important public health concerns. Oxidative stress has detrimental effects on bone metabolism, and serum uric acid (UA) is known to be a strong endogenous antioxidant. In the present study, we performed a large longitudinal study with an average follow-up period of 3 years to clarify the role of UA on the risk of incident osteoporotic fractures (OFs). METHODS: A total of 16,078 Korean men aged 50 years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after the baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea by using selected International Classification of Diseases, 10th revision codes. RESULTS: In total, 158 (1.0 %) men developed incident OFs. The event rate was 33.1 per 10,000 person-years. Subjects without incident OFs had 6.0 % higher serum UA levels than subjects with OFs (P = 0.001). Multivariable-adjusted Cox proportional hazard analyses adjusted for age, body mass index, glomerular filtration rate, lifestyle factors, medical and drug histories, and the presence of baseline radiological vertebral fractures revealed that the hazard ratio per standard deviation increase of baseline UA levels for the development of incident OFs was 0.829 (95 % CI = 0.695-0.989, P = 0.038). CONCLUSIONS: These data provide the epidemiological evidence that serum UA may act as a protective factor against the development of incident OFs in Korean men.

Preparation and characterization of carbon-titania nanocomposite-supported Pd3Co alloy nanoparticles for oxygen reduction.

A TiO2-modified carbon (C-TiO2) has been employed as a catalyst support of Pd3Co alloy for electroduction of oxygen. Due to the strong interaction between highly dispersed TiO2 and Pd3Co alloy, the C-TiO2 support was shown to be effective for a fine dispersion of Pd3Co alloys. The degree of sintering of Pd3Co on C-TiO2 could largely decrease during heat-treatment for reduction compared to that on unmodified carbon support (C). In oxygen reduction reaction (ORR), the reduced catalysts (Pd3Co/C-X and Pd3Co/C-TiO2-X; X represents reduction temperature) showed higher catalytic performance than their as-prepared catalysts. The catalytic activities of Pd3Co/C-TiO2-X were largely enhanced compared to those of Pd3Co/C-X. The ORR activity was measured to be the highest on Pd3Co/C-TiO2-300, which was 9 times enhanced activity (at 0.85 V) relative to the best-performed catalyst supported on carbon (Pd3Co/C-400). A positive role of TiO2 for the metal dispersion, the retardation of metal growth during heat-treatment, and the modification of electronic structure of Pd3Co was responsible for the enhanced ORR performance on Pd3Co/C-TiO2-X.

Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women.

UNLABELLED: Higher serum uric acid (UA) was associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in postmenopausal women. Furthermore, UA suppressed osteoclastogenesis and decreased production of reactive oxygen species in osteoclast precursors, indicating UA may have beneficial effects on bone metabolism as an antioxidant. INTRODUCTION: UA is known to play a physiological role as an antioxidant, and oxidative stress has detrimental effects on bone metabolism. In the present study, we investigated the association of serum UA level with the osteoporosis-related phenotypes and its direct effect on bone-resorbing osteoclasts using in vitro systems. METHODS: This is a large cross-sectional study, including 7,502 healthy postmenopausal women. Bone mineral density (BMD) and serum UA concentrations were obtained from all subjects. Data on bone turnover markers and lateral thoracolumbar radiographs were available for 1,023 and 6,918 subjects, respectively. An in vitro study investigated osteoclastogenesis and reactive oxygen species (ROS) levels according to UA treatment. RESULTS: After adjusting for multiple confounders, serum UA levels were positively associated with BMD at all sites (all p < 0.001). Compared with the participants in the highest UA quartile, the odds for osteoporosis were 40 % higher in those in the lowest quartile. The serum UA levels were inversely related to both serum C-terminal telopeptide of type I collagen and osteocalcin levels (p < 0.001 and p = 0.004, respectively). Consistently, subjects with vertebral fracture had lower serum UA levels, compared with those without it (p = 0.009). An in vitro study showed that UA decreased osteoclastogenesis in a dose-dependent manner and reduced the production of ROS in osteoclast precursors. CONCLUSION: These results provide epidemiological and experimental evidence that serum UA may have a beneficial effect on bone metabolism as an antioxidant in postmenopausal women.

Relative contributions of insulin resistance and ß-cell dysfunction to the development of Type 2 diabetes in Koreans.

AIMS: Controversies still exist regarding the relative contributions of insulin resistance and ß-cell dysfunction to the pathogenesis of Type 2 diabetes in different populations. We examined the associations of baseline insulin resistance and ß-cell function indices with the development of Type 2 diabetes in Koreans. METHODS: We analysed the clinical and laboratory data of 17 878 Korean adults (age 20-79 years) who underwent routine medical examinations with a median interval of 3.5 years (range 2.5-4.7 years). Using the homeostasis model assessment, insulin resistance (HOMA-IR) and ß-cell function (HOMA-%B) indices at baseline were assessed. RESULTS: Those who developed diabetes (n = 732, 4.1%) had significantly higher fasting serum insulin level (53.4 ± 31.2 vs. 41.4 ± 23.4 pmol/l) and HOMA-IR (2.38 ± 1.45 vs. 1.65 ± 1.02) and lower HOMA-%B (74 ± 47 vs. 85 ± 48) at baseline (P < 0.001 for all). Both high HOMA-IR and low HOMA-%B were independently associated with an increased odds ratio of incident Type 2 diabetes. Among the participants who developed diabetes, 29% demonstrated predominant ß-cell dysfunction (HOMA-%B < 25th percentile) and 51% had predominant insulin resistance (HOMA-IR > 75th percentile). When we divided the participants according to the median BMI of the whole population (23.7 kg/m²), 49% of participants in the low BMI group demonstrated predominant ß-cell dysfunction and 26% had predominant insulin resistance, whilst 21% in the high BMI group demonstrated mainly ß-cell dysfunction and 60% had mainly insulin resistance. CONCLUSIONS: In individuals with low BMI, ß-cell dysfunction is the predominant defect, whereas insulin resistance is the predominant pathogenetic factor in individuals with high BMI in the development of Type 2 diabetes in Koreans.

Association between metabolic syndrome and bone loss at various skeletal sites in postmenopausal women: a 3-year retrospective longitudinal study.

UNLABELLED: Although the presence of metabolic syndrome (MetS) and increasing numbers of MetS components were associated with attenuated bone loss at various skeletal sites in postmenopausal women, this beneficial effect of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects. INTRODUCTION: Previous cross-sectional epidemiological studies reported the inconsistent results regarding the combined effects of MetS on bone mass. In our present report, we performed a large, longitudinal study to evaluate MetS in relation to annualized bone mineral density (BMD) changes in postmenopausal Korean women. METHODS: The study cohort consisted of 1,218 postmenopausal women who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. The BMD at the lumbar spine and proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and at follow-up. RESULTS: Following adjustment for age, baseline BMD, and lifestyle factors, the women with MetS had 21.7, 17.0, 26.7, and 31.1 % less bone loss at the total femur, femur neck, trochanter, and lumbar spine, respectively, compared with MetS-free women (P = 0.004 to 0.041). Consistently, the rates of bone loss at all skeletal sites were linearly attenuated with increasing numbers of MetS components (P = 0.004 to <0.001). Importantly, when weight and height were added as confounding factors, the differences and trends of annualized BMD changes according to the MetS status disappeared. CONCLUSION: Our current results indicate that the beneficial effects of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects. Consequently, MetS per se may not be a meaningful concept for predicting future bone loss and for explaining associations between osteoporosis and cardiovascular diseases.

Effects of sirtuin 1 activation on nicotine and lipopolysaccharide-induced cytotoxicity and inflammatory cytokine production in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Although sirtuin 1 (SIRT1) over-expression and resveratrol exert anti-inflammatory and proinflammatory effects, their effects and the mechanism of action on human gingival fibroblast (HGF)-mediated inflammation are unknown. The aim of this study was to demonstrate the effects of activating SIRT1 using resveratrol and recombinant adenovirus encoding SIRT1 (Ad-SIRT1) on the expression of proinflammatory cytokines and to elucidate its mechanism of action of lipopolysaccharide (LPS) and nicotine stimulated-HGF. MATERIAL AND METHODS: Cytotoxicity and the production of reactive oxygen species (ROS) were measured using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The amount of prostaglandin E2 (PGE2 ) released into the culture medium was measured by radioimmunoassay. mRNA and protein levels were analyzed using RT-PCR and western blotting, respectively. RESULTS: Nicotine and LPS up-regulated the expression of SIRT1 mRNA and SIRT1 protein in a time- and concentration-dependent manner. Resveratrol and Ad-SIRT1 decreased LPS and nicotine-induced cytotoxicity, ROS and PGE2 production, and expression of cyclooxygenase-2 in HGFs. Resveratrol and Ad-SIRT1 inhibited nicotine and LPS-mediated protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), p38, ERK, JNK, MAPK and nuclear factor-kappa B (NF-κB) activation. CONCLUSION: This study is the first to show that the anti-inflammatory and cytoprotective effects of SIRT1 activation in HGFs occur through the PKC, PI3K, MAPK and NF-κB pathways.

Microencapsulation of pancreatic islets with canine ear cartilage for immunoisolation.

Improving human islet transplantation is often limited by the shortage of donors and the side effects of immunosuppressive agents. If immunoisolation is properly used, it can overcome these obstacles. Because artificial materials are adopted in this technique, however, there are still multiple issues with biocompatibility and foreign body reactions. We developed a chondrocyte microencapsulated immunoisolated islet (CMI-islet) that allows living cells to act as the immunoisolating material. To manufacture CMI-islets for xenotransplantation, isolated rat pancreatic islets were placed on low cell-binding culture dishes. Subsequently, expanded canine auricular cartiage primary cells were seeded on these dishes at a high density and maintained in a suspended state via a shaking culture system. Morphological evaluations showed good islet viability and a clear progression of the islet- encapsulation events. When the cells were challenged with glucose, they were able to secrete sufficient insulin according to glucose concentrations. The CMI-islets responded better to the glucose challenge than did nude pancreatic islets and created better glucose-insulin feedback regulation. Moreover, insulin secretion into the culture medium was confirmed over a period of 100 days, showing the survival and secretory capacity of the CMI-islet cells. By microencapsulating pancreatic islets with recipient ear cartilage cells, long-term insulin secretion can be maintained and the response to glucose challenges improved. This new immunodelusion technology differs from other immunoisolation techniques in that the donor tissue is enclosed with the recipient's tissue, thus allowing the transplanted cells to be recognized as recipient cells. This microencapsulation method may lead to developing viable xenotransplantation techniques that do not use immunosuppressive drugs.

Hybrid cellular spheroids from hepatocellular carcinoma and insulin-secreting cell lines.

During islet transplantation into the portal vein of the liver, the islet cells are expected to have complex interactions with hepatocytes. However, the mechanism underlying this interaction is not yet understood. Hence, we developed cellular complexes containing a mixture of human hepatocellular carcinoma cell line (Hep-G2) and rat insulin-secreting cell line (RIN-5F) by using a co-culture model and studied the function and morphology of the resultant hybrid cellular spheroids (HCSs). The RIN-5F and Hep-G2 cells were suspension cultured and, within 5 days of culture, the two types of cells aggregated to yield spheroids. The functionality of the thus formed HCSs was evaluated by measuring the levels of insulin and albumin in the culture supernatant. The HCSs retained their insulin- and albumin-secreting ability and their morphology, as revealed by immunohistological staining. The insulin and albumin levels secreted by the HCSs were considerably higher than those secreted by spheroids of single-cell origin. Generally, obtaining complexes from more than two types of cells is difficult. However, we were able to generate HCSs. We believe that this culture method could have various applications such as studying the in vitro cell-cell interactions and developing new cell transplantation models.

Long-term viability of transplanted hybrid cellular spheroids within chondrocyte sheets.

Encapsulation of transplanted cells within an immunoisolating membrane may provide a new strategy for protecting these cells from recipient immune responses without the use of immunosuppressive drugs. We have previously reported a novel concept of immunoisolation and immunodelusion using recipient cells instead of traditional artificial materials. We developed a chondrocyte sheeting immunodelusive immunoisolated bioartificial pancreas (CSI-BAP) that would enable transplantation of cells across allogeneic and xenogeneic barriers without the cells being recognized as donor cells and without the need for immunosuppression. Recently, we have constructed hybrid cellular spheroids (HCSs) containing cells from two different cell lines (RIN-5F, an insulin-secreting cell line, and Hep-G2, a hepatocellular carcinoma cell line) to enhance the function and biocompatibility of the HCSs. These HCSs were then encapsulated with multiple layers of chondrocyte sheets obtained from the auricular cartilage of Sprague-Dawley (SD) rats. The in vitro ability of the CSI-BAP to secrete insulin was tested before transplantation. Histological evaluation of CSI-BAP chondrocyte microencapsulated immunoisolated islet morphology and viability of allogeneic or xenogeneic cell lines was performed 100 days after the CSI-BAP was transplanted into SD rats. Morphological evaluations revealed good viability of the islets and progression of islet encapsulation. In vitro insulin secretion from the CSI-BAP was well maintained. Additionally, insulin and albumin secretion from the CSI-BAP was confirmed by in vivo immunohistochemical examination. Moreover, the cell lines transplanted into the subcutaneous space in the form of HCSs within the chondrocyte sheets showed good viability of more than 100 days and sustained insulin and albumin secreting ability.

Impact of body mass index on the predictive ability of body fat distribution for type 2 diabetes risk in Koreans.

AIMS: The optimal anthropometric measure of obesity or body fat distribution that best predicts the risk of Type 2 diabetes in Asians is unclear. Moreover, it has not been determined whether BMI modifies the effect of body fat distribution on diabetes risk in Asians. METHODS: We analysed the anthropometric and laboratory data of 7658 non-diabetic Korean adults (5061 men and 2597 women, aged 20-79 years) who underwent routine medical check-ups at 5-year intervals. BMI, waist circumference, waist-to-height ratio, and bioelectrical impedance (to calculate fat mass and per cent body fat) were measured at baseline. RESULTS: Of the 7658 participants, 278 subjects (3.6%) developed diabetes over 5 years. Each of the anthropometric measures of general obesity (BMI, fat mass, per cent body fat) and central body fat distribution (waist circumference and waist-to-height ratio) was a good predictor of Type 2 diabetes. However, when the areas under the receiver-operating characteristic curves were compared, BMI (0.697; 95% CI, 0.669-0.725), waist circumference (0.709, 0.682-0.736) and waist-to-height ratio (0.718, 0.692-0.743) were better predictors of diabetes risk than fat mass (0.672, 0.643-0.700) or per cent body fat (0.657, 0.628-0.686). In the low- (< 23 kg/m(2)) and mid- (23-27 kg/m(2)) BMI groups, the addition of waist-to-height ratio or waist circumference to BMI could improve the prediction of diabetes risk. CONCLUSIONS: BMI, waist circumference and waist-to-height ratio were good predictors of Type 2 diabetes risk in Koreans. In non-obese or less obese subjects, measures of central body fat distribution can help improve the prediction of Type 2 diabetes risk when added to measures of general obesity.

Association of restrictive ventilatory dysfunction with insulin resistance and type 2 diabetes in koreans.

AIMS: To investigate associations of obstructive and restrictive patterns of ventilatory dysfunction with insulin resistance and type 2 diabetes mellitus (DM) in Koreans. METHODS: We cross-sectionally examined clinical, laboratory, and pulmonary function data on 35,456 Korean adults (age 18-93 years, 40% women) recorded during regular health check-ups. Insulin resistance (IR) was determined from fasting serum insulin concentration and homeostasis model assessment (HOMA). RESULTS: Individuals with type 2 DM and those with pre-diabetes (impaired fasting glucose levels) showed a higher prevalence of both restrictive (18% and 11%, respectively, VS. 8%; P<0.01) and obstructive (4.3% and 3.2%, respectively, VS. 2.3%; P<0.01) ventilatory dysfunction than did individuals with normal fasting glucose levels. Compared to subjects with normal ventilatory function, those with restrictive or obstructive ventilatory dysfunction were older, had higher systolic and diastolic blood pressure, and had elevated glucose and HbA1c levels. However, serum triglyceride, fasting insulin, and HOMA-IR were higher only in subjects with restrictive ventilatory dysfunction, and not in those with obstructive ventilatory dysfunction. On logistic regression analysis, the age and gender-adjusted odds ratio (OR) of restrictive ventilatory dysfunction for type 2 DM was 1.59 (95% confidence interval, 1.43-1.78). The increased OR remained significant after controlling for exercise, drinking, and smoking habits, presence of hypertension, body mass index, and waist circumference (OR=1.38 [1.23-1.55]). However, further adjustment for HOMA-IR attenuated the OR (1.11 [0.97-1.26]), making the OR statistically insignificant. In contrast, obstructive ventilatory dysfunction was not independently related to type 2 DM status. CONCLUSION: Restrictive ventilatory dysfunction is independently associated with type 2 DM, probably VIA insulin resistance.

The association between serum osteocalcin levels and metabolic syndrome in Koreans.

UNLABELLED: The association between serum osteocalcin levels and metabolic syndrome (MS) in Korean individuals was investigated. Serum osteocalcin levels are significantly lower in subjects with MS than in those without the disease, regardless of glucose metabolism. INTRODUCTION: Osteocalcin was recently shown to affect energy metabolism. In the present study, we investigated the possible association between serum osteocalcin concentrations and MS. METHODS: A cross-sectional community-based survey was conducted. Serum osteocalcin, type 1 collagen C-telopeptide (CTX) and total alkaline phosphatase (ALP) concentrations were determined in 567 subjects. MS was defined according to NCEP-ATP III criteria. RESULTS: Serum osteocalcin concentrations were significantly lower in subjects with MS than those without MS in postmenopausal women (18.923 ± 7.685 vs 22.513 ± 7.344 ng/ml, P<0.001) and marginally lower in subjects with MS than those without MS in men (14.550 ± 5.090 vs 16.125 ± 4.749 ng/ml, P=0.086) after adjustment for age and BMI. Further controlling with CTX or ALP did not affect this association in postmenopausal women; however, controlling with osteocalcin abolished the association between CTX and MS. Significant differences in serum osteocalcin levels by MS status were noted in subjects with normal glucose tolerance as well as those with abnormal glucose tolerance (P=0.032 and P<0.001, respectively). Compared with subjects with the highest quartile of osteocalcin, those in the lower quartile groups (Q1-Q3) had significantly increased risks of MS (ORs=5.18, CIs=1.15-23.42) in men. In postmenopausal women, the ORs for MS were significantly higher in the lowest quartile than in the highest quartile (ORs=5.25, CIs=2.42-11.36). CONCLUSIONS: These findings suggest that osteocalcin is associated with MS, independently of glucose metabolism.

The efficacy of intravenous ketorolac for pain relief in single-stage adjustable strabismus surgery: a prospective, randomized, placebo-controlled trial.

PURPOSE: To determine the efficacy of preoperative intravenous ketorolac in reducing intraoperative and postoperative pain and improving patient satisfaction in patients undergoing single-stage adjustable strabismus surgery. METHODS: A prospective, randomized, placebo-controlled clinical trial was performed with 67 patients who underwent horizontal recti muscle surgery with adjustable sutures. The test group received intravenous ketorolac (60 mg) before surgery, and the control group received intravenous normal saline. Topical 0.5% proparacaine was administered to both groups during surgery. Vital signs including heart rate and blood pressure were recorded every 10 min throughout the surgery. The patients were asked to rate their maximum intraoperative and postoperative pain scores using a numerical pain rating scale. Patient satisfaction was also assessed using a five-point analogue scale. RESULTS: The ketorolac-premedicated patients had less pain both during and after surgery (P = 0.033 and P = 0.024, respectively). There were no differences in vital signs during surgery and patient satisfaction between the two groups. CONCLUSIONS: Intravenous ketorolac, when administered preoperatively for single-stage adjustable strabismus surgery under topical anaesthesia, was effective in reducing pain during and after surgery.

Autoantibody against activating transcription factor-2 in patients with systemic sclerosis.

OBJECTIVES: To determine the prevalence and clinical correlation of autoantibody to activating transcription factor (ATF)-2, a transcription factor of ATF/CREB family, in patients with systemic sclerosis (SSc). METHODS: Anti-ATF-2 Ab was examined by ELISA and immunoblotting using human recombinant ATF-2. ATF-2 activity to bind target DNA was evaluated by ELISA using a plate coated with oligonucleotide containing the consensus binding site for ATF-2. RESULTS: IgG anti-ATF-2 Ab levels in SSc patients (n=69) were significantly higher than those in normal controls (n=26). SSc patients positive for IgG anti-ATF-2 Ab had significantly longer disease duration, more frequent presence of decreased %VC and %DLco, and elevated levels of serum IgG, serum IgA, and erythrocyte sedimentation rates than those negative. More-over, IgG anti-ATF-2 Ab levels correlated inversely with %VC or %DLco. The presence of anti-ATF-2 Ab in SSc patients was confirmed by immunoblotting analysis. IgG isolated from serum samples of SSc patients positive for IgG anti-ATF-2 Ab by ELISA slightly but significantly inhibited ATF-2 activity compared with normal controls. CONCLUSIONS: These results suggest that anti-ATF-2 Ab is a new autoantibody in SSc and that it serves as a novel serological marker for inflammation and lung involvement in SSc.

Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide.

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO-1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO-1 stimulator and HO-1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor-alpha, interleukin-6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO-1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO-1 inhibitor. These results suggest that the HO-1/CO signalling pathway is a therapeutic target for human IC-mediated disease.

Decreased cerebral blood flow of thalamus in PTSD patients as a strategy to reduce re-experience symptoms.

OBJECTIVE: To investigate alterations of regional cerebral blood flow (rCBF) in subjects with post-traumatic stress disorder (PTSD). METHOD: Using [99Tcm]-hexamethyl propylenamino oxime single photon emission computed tomography, the rCBF under resting condition was compared between 19 survivors of the Taegu subway fire with PTSD and 19 comparison subjects. RESULTS: PTSD patients showed a decreased rCBF in the right thalamus and an increased rCBF in the right superior parietal lobe relative to comparison subjects (corrected P < 0.05). The rCBF in the right thalamus positively correlated with the severity of current re-experience symptoms in PTSD subjects. CONCLUSION: Our finding of the thalamic rCBF decrease in PTSD patients may be a strategy to reduce re-experience symptom, by evading the process of external and internal information which can evoke traumatic memory. In addition, the parietal rCBF increase in our PTSD patients might be related to altered information processing in PTSD.