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Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. Among high-risk postmenopausal East Asian women, romosozumab followed by alendronate was associated with lower incidences of fractures vs alendronate alone. Romosozumab demonstrates potential to address an unmet need in osteoporosis management in Asia., Introduction: Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. The global ARCH study demonstrated superiority of romosozumab followed by alendronate in reducing fracture risk in high-risk postmenopausal osteoporotic women vs alendronate alone. We report outcomes among ARCH East Asian patients., Methods: In ARCH, 4093 postmenopausal osteoporotic women with fragility fracture were randomized 1:1 to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, both followed by open-label alendronate. Primary endpoints were incidence of new vertebral fracture (VF) at 24 months and clinical fracture at primary analysis (confirmed fractures in ≥ 330 patients and all patients had opportunity to attend month 24 visit). This post hoc analysis was not powered to detect fracture-rate differences., Results: This analysis included 275 patients from Hong Kong, Korea, and Taiwan. Romosozumab followed by alendronate reduced risk of new VFs at 24 months by 60% (P = 0.11) and clinical fractures at primary analysis by 44% (P = 0.15) vs alendronate alone. Romosozumab followed by alendronate significantly increased mean bone mineral density at 24 months from baseline by a further 9.0%, 3.3%, and 3.0% at the lumbar spine, total hip, and femoral neck vs alendronate alone. Adverse event (AE) rates, including positively adjudicated serious cardiovascular AEs (1.6% vs 1.4% at 12 months for romosozumab vs alendronate), were similar across treatment groups., Conclusions: Consistent with the global analysis, romosozumab followed by alendronate was associated with lower incidences of new vertebral, clinical, non-vertebral, and hip fractures vs alendronate alone among East Asian patients.

In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance., Purpose: We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort., Methods: We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht 2 ) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB)., Results: Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht 2 , stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht 2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht 2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht 2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates., Conclusion: Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.

Dietary potassium may neutralize acid load and reduce calcium loss from the bone, leading to beneficial effect on bone mineral density. In this nationwide Korean population study, dietary potassium intake was associated with improved bone mineral density in older men and postmenopausal women., Introduction: Nutrition is a major modifiable factor that affects bone health. The accompanying anion in dietary potassium may act as an alkaline source by neutralizing the acid load and reducing calcium loss from the bone. We aimed to evaluate the association between dietary potassium intake and bone mineral density (BMD) in the Korean population., Methods: We analyzed a total of 3135 men aged >50 years and 4052 postmenopausal women from the Korean National Health and Nutrition Examination Survey (KNHANES). Lumbar spine, total hip, and femur neck BMD were measured using dual energy X-ray absorptiometry. The daily food intake was assessed using a food frequency questionnaire., Results: When we divided the participants into tertiles based on the intake of potassium intake, the highest potassium intake tertile group showed a significantly higher total hip and femur neck BMD as compared to lower tertile groups (0.914 ± 0.004, 0.928 ± 0.003, 0.925 ± 0.004 mg/day across the tertiles, P = .014 for total hip; 0.736 ± 0.003, 0.748 ± 0.003, 0.750 ± 0.004 mg/day, P = .012 for femur neck). Postmenopausal women in the highest potassium intake tertile group showed significantly higher lumbar, total hip, and femur neck BMD as compared to those in lower potassium intake tertile groups (0.793 ± 0.004, 0.793 ± 0.003, 0.805 ± 0.004 mg/day across the tertiles, P = .029 for lumbar spine; 0.766 ± 0.003, 0.770 ± 0.002, 0.780 ± 0.003 mg/day, P = .002 for total hip; 0.615 ± 0.003, 0.619 ± 0.002, 0.628 ± 0.003 mg/day, P = .002 for femur neck)., Conclusions: Dietary potassium intake was positively associated with BMD in men aged >50 years and postmenopausal women, indicating the beneficial effects of dietary potassium intake on bone health.

Little is known about the association between vitamin D deficiency and the skeletal phenotypes in primary hyperparathyroidism (PHPT) patients. A low 25-hydroxyvitamin D level was associated with a low bone mineral density and deteriorated hip geometry in women with PHPT in an Asian population where vitamin D deficiency is prevalent., Introduction: Few studies have examined the effect of vitamin D deficiency on the bone health of primary hyperparathyroidism (PHPT) patients., Methods: We investigated the skeletal effects of vitamin D deficiency in 79 PHPT patients by assessing bone mineral density (BMD), the trabecular bone score (TBS), and hip geometry, which were measured using dual-energy X-ray absorptiometry (27 men with median age 60 years [53;69]; 52 postmenopausal women with median age of 57 years [53;67]). Cross-sectional data were collected from subjects enrolled in an ongoing PHPT cohort study at Seoul National University Hospital from March 2008 to December 2015., Results: We classified PHPT patients according to 25-hydroxyvitamin D (25(OH)D) levels (<20 vs. ≥20 ng/ml). After adjusting for age and body mass index, women with vitamin D deficiency had lower BMDs at the lumbar spine (LS) and femur neck (FN) than women who had sufficient levels of vitamin D (LS, 0.903 ± 0.138 vs. 0.998 ± 0.184 g/cm 2 ; FN, 0.715 ± 0.084 vs. 0.791 ± 0.113 g/cm 2 ; P < 0.05). However, the total hip BMD and the TBS were not significantly different between the two groups. In the hip geometry analysis, the cross-sectional area, cross-sectional moment of inertia, and section modulus were also significantly lower in women with vitamin D deficiency than in those without. No significant difference was found in the BMD, TBS, or hip geometry according to 25(OH)D levels in men., Conclusion: Vitamin D deficiency may be associated with a low BMD and deteriorated hip geometry in postmenopausal women with PHPT.

In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index., Introduction: AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer., Methods: We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry., Results: BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD., Conclusions: Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.

This study evaluated the use of low-dose chest computed tomography (LDCT) for detecting bone fragility. LDCT-measured vertebral bone attenuation by volumetric methods showed good correlation with bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA, and good diagnostic performance for identifying osteoporosis and compression fractures. The results of this study suggest the feasibility of obtaining comprehensive information on bone health in subjects undergoing LDCT., Introduction: Osteoporosis is a prevalent but underdiagnosed disease that increases fracture risk. This study evaluated the utility of vertebral attenuation derived from low-dose chest computed tomography (LDCT) compared to dual-energy x-ray absorptiometry (DXA) for detecting bone fragility., Methods: A total of 232 subjects (78 men and 154 women) aged above 50 years who underwent both LDCT and DXA within 30 days were evaluated. LDCT-measured bone attenuation in Hounsfield units (HU) of four vertebrae (T4, T7, T10, and L1) was evaluated using volumetric methods for correlation with DXA-measured bone mineral density (BMD) and for the diagnosis of compression fractures, osteoporosis, and low BMD (osteoporosis or osteopenia) in men and women, with DXA measurements as the reference standard., Results: The average attenuation of the four vertebrae showed strong correlation with DXA-measured BMD of the lumbar spine (r = 0.726, p < 0.05). In receiver-operating characteristic (ROC) analyses, the area under the curve (AUC) across LDCT-measured thresholds of the average attenuation to distinguish compression fractures was 0.827, and a threshold of 129.5 HU yielded 90.9 % sensitivity and 64.4 % specificity. Similarly, average attenuation showed high AUCs and good diagnostic performance for detecting osteoporosis and low BMD in both men and women. Among 44 subjects with compression fractures, the average bone attenuation showed strong negative correlation with both the worst fracture grade (r = -0.525, p < 0.05) and cumulative fracture grade score (r = -0.633, p < 0.05)., Conclusion: LDCT-measured bone attenuation by volumetric methods showed good correlation with BMD measured by DXA and good diagnostic performance for identifying bone fragility.

Unlabelled: The effects of diabetes medications on risk of fracture were investigated using the South Korea nationwide claims database. We demonstrated that the use of dipeptidyl peptidase-4 inhibitor could be associated with decreased risk of fracture. Thiazolidinedione use was associated with about 60 % increased risk of fracture in real clinical practice., Introduction: The effects of diabetes medication on fracture have important clinical health consequences, since most diabetes patients are at high risk of fracture. We aimed to investigate the effect of diabetes medication on fracture risk., Methods: The nationwide medical claim database in South Korea was investigated. Among 2,886,555 subjects with antidiabetes prescriptions, 207,558 subjects aged 50 years and older, who initiated diabetes medication from 2008 to 2011, were analyzed. The subjects were classified based on diabetes medication classes: non-user (insufficient exposure), metformin (MET), sulfonylurea (SU), alpha-glucosidase inhibitor (AGI), MET + SU, MET + thiazolidinedione (TZD), MET + dipeptidyl peptidase-4 inhibitor (DPP4-I), and SU + TZD., Results: A total of 5996 fractures were observed. The fracture rate varied significantly across type of diabetes medications, with MET + DPP4-I combination group having the lowest rate and SU + TZD combination group having the highest rate. Compared to non-users, MET + DPP4-I inhibitor combination group had significantly reduced composite fracture risk (hazard ratio (HR) = 0.83, P = 0.025) and significantly reduced vertebral fracture risk (HR = 0.73, P = 0.013) in the unadjusted analysis. Compared to MET + SU users, MET + DPP4-I users showed a trend of lower non-vertebral fracture risk (HR = 0.82, P = 0.086) after adjusting for all confounding variables. Patients using TZD had significantly increased risk of fracture (HR = 1.59, P < 0.001) compared with patients not using TZDs adjusting for all confounding variables., Conclusions: The results of this nationwide study showed a trend that DPP4 inhibitor might have a protective effect on bone metabolism compared with SU, when added to MET. Clinicians should take these results into consideration when prescribing diabetes medication, especially in elderly patients or those at high risk or fracture.

Unlabelled: A daughter's bone mineral density (BMD) is significantly correlated with her mother's BMD, but the daughter's body mass index (BMI) could modulate this association. Maternal inheritance dominantly affects daughters with a lower BMI, but BMI could compensate for hereditary influences in daughters with a higher BMI in terms of daughter's BMD., Introduction: Achieving optimal peak bone mass at a young age is the best way to protect against future osteoporosis and subsequent fractures. Although environmental components influence bone mass accrual, but peak bone mass is largely programmed by inheritance. The aims of this study were to investigate the influence of maternal inheritance on the daughter's bone mass and to assess whether these influences differ according to the daughter's body mass index (BMI)., Methods: We used data obtained from the 2010 Korean National Health and Nutrition Examination Survey V and included 187 mother-daughter pairs. Bone mineral density (BMD) was measured at the lumbar spine (LS), femur neck (FN), and total hip (TH) by using dual-energy X-ray absorptiometry (DXA). The daughter group was stratified into two groups according to the mean BMI (21.4 kg/m(2))., Results: The daughters' BMD correlated significantly with both their BMI and their mothers' Z-score for each skeletal site. In the daughters with a lower BMI (≤21.4 kg/m(2)), the BMDs at the FN and TH were affected more by the mothers' Z-score than by the daughters' BMI. Meanwhile, the influence of the daughters' BMI on their BMD was higher than that of their mothers' Z-score in daughters with a higher BMI (>21.4 kg/m(2)). Moreover, the mothers' Z-scores were a significant predictor of their daughters having Z-scores < -1.0 only in daughters with a lower BMI., Conclusions: This study suggests that maternal inheritance is an important determinant of the daughters' bone mass, but that this hereditary factor may vary according to the daughters' BMI.

Summary: In a prospective community-based cohort study, we investigated the relationship between trabecular bone score (TBS) and regional fat depots in 1474 Korean postmenopausal women. TBS was positively related with subcutaneous fat and negatively related with visceral fat., Introduction: The effect of fat distribution (visceral/subcutaneous) on bone quality or microarchitecture has rarely been investigated due to measurement difficulty. We aimed to investigate the relationship between TBS reflecting bone microarchitecture and regional fat depots in Korean women., Methods: Cross-sectional data evaluation was made from subjects participating in an ongoing prospective community-based cohort study since 2001. A total of 1474 postmenopausal women in the Ansung cohort were analyzed. Regional body fat mass, bone mineral density (BMD) at the lumbar spine, and total hip and lumbar spine TBS were measured by dual energy X-ray absorptiometry (DXA)., Results: In an age-adjusted partial correlation analysis, TBS was not associated with total fat mass, but negatively associated with trunk fat mass. However, TBS was positively related with leg (r = 0.102, P < 0.05) and gynoid fat mass (r = 0.086, P < 0.05) and negatively related with android fat mass (r = -0.106; P < 0.05). In linear regression models controlling age, BMI, and physical activity, android fat was inversely associated with TBS (β = -0.595, P < 0.001), whereas gynoid fat was positively associated with TBS (β = 0.216, P < 0.001). Lumbar spine and total hip BMDs revealed positive associations with total and all regional fat depots regardless of fat distribution., Conclusion: Our findings suggest that relatively large visceral fat and small subcutaneous fat may have a detrimental effect on TBS, a bone microarchitecture index.

Summary: Our study showed that serum osteocalcin levels are closely related to glucose metabolism in men of all ages and younger women. This association disappeared in postmenopausal women in which increases bone turnover rates. The association between serum osteocalcin levels and glucose homeostasis should be interpreted according to age and sex., Introduction: Osteocalcin, a marker of bone formation, appears to be associated with glucose homeostasis. We investigated the age- and sex-specific association of serum osteocalcin level with variables related to glucose metabolism., Methods: This study was based on cross-sectional analysis from 719 participants aged 20-85 years after excluding patients taking antidiabetic or antiosteoporotic drugs. The subjects were divided into four groups according to age and sex as follows: men <50 years (n = 131), men ≥50 years (n = 191), women <50 years (n = 108), and women ≥50 years (n = 279). Anthropometric and biochemical variables including insulin resistance (HOMA-IR) and β cell function (HOMA-β) from a 75-g oral glucose tolerance test, and serum 25-OH-vitamin D and parathyroid hormone levels were measured., Results: The serum osteocalcin level was significantly higher in women aged ≥50 years compared with women <50 years (20.4 ± 7.8 vs. 17.9 ± 6.8 ng/ml, p < 0.001), but there was no difference between men aged ≥50 years and men <50 years (16.4 ± 5.9 vs. 16.8 ± 6.0 ng/ml, p = 0.905). The participants diagnosed with diabetes had lower serum osteocalcin levels than normal or prediabetic participants. Multivariable regression analyses including HOMA-IR and HOMA-β indicated that serum osteocalcin levels had a negative and independent association with HbA1c levels in men and women aged <50 years, but not in women ≥50 years., Conclusions: Low osteocalcin levels are associated with impaired glucose metabolism in men and premenopausal women. The osteocalcin levels may be determined by factors related to bone metabolism in postmenopausal women. Our data suggest that the serum levels of osteocalcin associated with glucose homeostasis should be interpreted according to age and sex.

Objective: To investigate the effects of single-dose intravenous dexamethasone on inflammatory responses, pain, nausea, and vomiting after uterine artery embolisation (UAE)., Design: Prospective, randomised, double-blind, and placebo-controlled study., Setting: Tertiary-care University centre in Korea., Population: Patients undergoing UAE for the treatment of symptomatic fibroids or adenomyosis., Methods: Patients were randomised to receive either intravenous dexamethasone (10 mg; dexamethasone group) or normal saline (control group) 1 hour before UAE. Both groups received fentanyl-based intravenous patient-controlled analgesia (PCA) during the 24 hours after UAE., Main Outcome Measures: The primary outcomes were the inflammatory and stress responses measured by white blood cell count, neutrophil percentage, C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol. Secondary outcomes were severity of pain and incidence of nausea and vomiting., Results: Sixty-four patients were enrolled and 59 patients completed the study. CRP, IL-6, and cortisol were significantly lower in the dexamethasone group compared with the control group during the 24 hours after UAE. Although the cumulative dose of fentanyl and additional analgesics administered during the 24 hours after UAE were similar between the two groups, pain scores were significantly lower in the dexamethasone group from 12 hours after UAE, and the incidence of severe nausea and vomiting was lower in the dexamethasone group., Conclusions: The administration of single-dose intravenous dexamethasone as an adjunct to fentanyl-based intravenous PCA is effective in reducing inflammation and pain during the first 24 hours after UAE., Tweetable Abstract: Dexamethasone is effective in reducing inflammation and pain after uterine artery embolisation., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Summary: Lumbar spine trabecular bone score (TBS) was significantly decreased in active acromegaly patients. TBS may be useful to assess the skeletal fragility in acromegaly in which bone mineral density (BMD) is not sufficient to represent bone strength and explain the high incidence of fragility fractures in acromegaly patients., Introduction: Although the data on BMD are controversial, patients with acromegaly have an increased risk of fragility fracture. We examined the lumbar spine TBS to explain the skeletal deterioration in acromegaly patients., Methods: We included 14 men and 19 women acromegaly patients who underwent dual-energy X-ray absorptiometry at the time of diagnosis from 2000 to 2014 at Seoul National University Hospital. Ninety-nine age-, sex- and body mass index-matched controls were recruited. Biochemical parameters, lumbar spine TBS, and BMD at all sites were measured. Gonadal status was evaluated at diagnosis., Results: Lumbar spine TBS was lower in acromegaly patients than in controls in both genders (1.345 ± 0.121 vs. 1.427 ± 0.087, P = 0.005 in men; 1.356 ± 0.082 vs. 1.431 ± 0.071, P = 0.001 in women). In contrast, BMD at all sites did not differ between the two groups. Hypogonadal acromegaly patients (men, n = 9; women, n = 12) had lower TBS values compared with controls both in men and women (all P < 0.05), although BMD at all sites were similar for the two groups. In eugonadal acromegaly patients, lumbar spine TBS was lower than in women controls only (P = 0.041)., Conclusions: Skeletal microarchitecture was deteriorated in acromegaly patients as assessed by TBS, which seems to be a consequence of growth hormone excess as well as hypogonadism, especially in women.

Unlabelled: Trabecular bone scores (TBS) have recently been developed as a diagnostic tool to assess bone texture. We studied thyroid status and TBS in a population-based cohort and demonstrated that high-normal thyroxine levels are associated with low TBS in healthy euthyroid postmenopausal women., Introduction: Increased thyroid hormone levels affect bone mineral density (BMD) and, if untreated, increase the risk of fracture. However, the relationship between thyroid function and bone microarchitecture has not yet been established. Trabecular bone scores (TBS) are gray-level textural measurements of dual energy X-ray absorptiometry (DXA) images. The TBS has been proposed as an indirect index of bone microarchitecture. The goal of this study was to characterize the relationship between thyroid function and TBS in euthyroid men and postmenopausal euthyroid women., Methods: A total of 1376 euthyroid subjects (648 postmenopausal women and 728 men) were recruited from a community-based cohort in Korea. Free thyroxine (fT4) levels, thyroid stimulating hormone (TSH) levels, BMD, and TBS were measured and compared., Results: There was no significant relationship between either fT4 or TSH levels and BMD in men and women. Multiple linear regression analysis showed that high-normal fT4 levels were negatively correlated with TBS (β = -0.111; P = 0.002, after adjusting for both age and body mass index [BMI]) in postmenopausal women. In men, however, there was no significant correlation between fT4 levels and TBS. TSH levels were not significantly associated with TBS in either men or women., Conclusion: Higher fT4 levels within the normal reference range are associated with deterioration of trabecular microarchitecture in healthy euthyroid postmenopausal women.

The Korean traditional hot sauce gochujang has been reported to have biological activities. Different kinds of gochujang products were prepared based on combinations of a fungal rice koji with two kinds of bacterial soybean mejus. Diets that included gochujang products were fed to rats and anti-obesity effects were investigated. Gochujang products reduced body weight gains, epididymal fat weights, and triglyceride levels in the serum and the liver. Effects were exerted by the diet that included the non-fermented gochujang mixture, increased using a fungal rice koji, and further enhanced using a bacterial soybean meju. Dietary effects were apparently induced via inhibition of the lipogenic enzymes fatty acid synthase, malic enzyme, and lipoprotein lipase by gochujang products in epididymal adipose tissues, and inhibition of glucose-6-phosphate dehydrogenase in the liver. High levels of capsaicin and genistein in gochujang products are considered to contribute to anti-obesity effects.

Unlabelled: Dietary vitamin C intake showed significant positive associations with BMD in postmenopausal women, especially with vitamin D deficiency., Introduction: Although there is a positive role of vitamin C in osteoblastogenesis, debate remains about the contribution of vitamin C to bone mineral density (BMD) in humans., Methods: Data were derived from the Fourth Korean National Health and Nutrition Examination Survey. Dietary information was assessed using a 24-h dietary recall questionnaire. BMD was measured by dual-energy X-ray absorptiometry at the lumbar and hip., Results: A total of 1,196 postmenopausal women aged 50 years and older were stratified into tertiles by daily dietary vitamin C intake. After adjusting for traditional confounders, dietary vitamin C intake tertile was significantly positively associated with BMD at all sites (R = 0.513 for lumbar spine (LS) and R = 0.657 for femoral neck (FN), P < 0.05 for each). The subjects with osteoporosis had significantly lower dietary vitamin C intake than did subjects without osteoporosis (74.4 ± 66.2 vs 94.1 ± 78.6 mg/day for LS and 65.5 ± 56.6 vs 94.3 ± 79.2 mg/day for FN, respectively, P < 0.001). The multiple-adjusted odds ratio for osteoporosis for dietary vitamin C <100 mg/day was 1.790 (95 % CI 1.333-2.405, P < 0.001). However, the significant association between vitamin C intake and BMD was only observed in subjects with vitamin D deficiency and aged 50-59 years or >70 years., Conclusion: Dietary vitamin C intake was positively associated with BMD in postmenopausal women, and inadequate vitamin C intake could increase the risk of osteoporosis.

Posterior neck pain following thyroidectomy is common because full neck extension is required during the procedure. We evaluated the effect of intra-operative transcutaneous electrical nerve stimulation on postoperative neck pain in patients undergoing total thyroidectomy under general anaesthesia. One hundred patients were randomly assigned to one of two groups; 50 patients received transcutaneous electrical nerve stimulation applied to the trapezius muscle and 50 patients acted as controls. Postoperative posterior neck pain and anterior wound pain were evaluated using an 11-point numerical rating scale at 30 min, 6 h, 24 h and 48 h following surgery. The numerical rating scale for posterior neck pain was significantly lower in the transcutaneous electrical nerve stimulation group compared with the control group at all time points (p < 0.05). There were no significant differences in the numerical rating scale for anterior wound pain at any time point. No adverse effects related to transcutaneous electrical nerve stimulation were observed. We conclude that intra-operative transcutaneous electrical nerve stimulation applied to the trapezius muscle reduced posterior neck pain following thyroidectomy., (© 2014 The Association of Anaesthetists of Great Britain and Ireland.)

Aim: To evaluate the effect of reciprocating amplitude and progressive angular increment on fatigue life enhancement of NiTi rotary endodontic instruments., Methodology: ProTaper F2 instruments were operated in steel artificial canals with both stationary reciprocating (SR) and progressive reciprocating (PR) motions. The SR motions involved symmetric to and fro reciprocation of ± 180(o) , ± 135(o) , ± 90(o) , ± 60(o) and ± 45(o) . The PR motions were ± 45(o) stationary motion superimposed with angular increments of 7(o) , 11(o) , 22.5(o) or 31(o) whenever an instrument completed 1, 10 or 30 reciprocating cycles (rc). The fatigue lives were compared with those under continuous rotation (CR) and a reciprocating operation with a forward 144(o) and backward 72(o) motion proposed by Yared (2008). The statistical significance of these operating modes on fatigue life was examined using one way anova and post hoc Tukey's tests at P = 0.05. Fractographic analysis was also applied to probe the fracture mechanisms of different rotation motions., Results: Fatigue life increased with decreasing reciprocating amplitude. Operating in the SR increased fatigue life by 355% over that in the CR. Except for the 22.5(o) increment, all PR motions yielded longer fatigue lives than the SR motion. A progressive reciprocating operation with a ± 45(o) reciprocating amplitude and a + 7(o) progressive angular increment every 10 reciprocating cycles (± 45(o) /10rc/+7(o) ) increased fatigue life by 990% over that in the CR motion. In terms of life enhancement over the CR motion, the larger the curvature the less are the differences between different movements. Single crack initiation sites were found in the CR and SR motions, while three crack initiation sites were typical in the ± 45(o) /10rc/+7(o) motion., Conclusions: Fatigue life increased with decreasing reciprocating amplitude in stationary reciprocation. A progressive reciprocating operation with ± 45(o) /10rc/+7(o) motion led to significant fatigue life enhancement and multiple fatigue crack initiation in NiTi endodontic instruments., (© 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Unlabelled: We determined the incidence of second hip fracture and evaluated whether compliant and persistent users of bisphosphonate had a lower incidence of second hip fracture after prior hip fracture, from a national claim registry., Introduction: Bisphosphonate is prescribed worldwide for the primary prevention of osteoporotic fracture. However, the association between adherent use of bisphosphonate and prevention of second hip fracture is unclear. Our purpose was to determine whether the adherent use of bisphosphonate was associated with a decreased risk of second hip fracture in South Korea, using a nationwide database., Methods: From 2007 to 2011, first and second hip fractures were identified using the ICD-10 and procedure code form from the nationwide database of the Health Insurance Review and Assessment Service. Compliant use of bisphosphonate was defined as a patient medication possession ratio of 80 or more. Persistent users were defined patients with a refill gap of 30 days or less. We compared the incidence of second hip fracture in compliant and persistent users and non-users., Results: Among 59,782 patients with first hip fracture, in this study, 1,336 second hip fracture occurred after the initial hip fracture during the study period. The mean age at the first hip fracture was 75.4 years (range, 50 to 100 years). The cumulative 1-year, 2-year, and 3-year incidence of second hip fracture was 1.0% (552/59,782), 1.9% (1,123/59,782), and 2.2% (1,336/59,782), respectively. After multivariate analysis, compliant and persistent use of bisphosphonate was significantly independent protectors for second hip fracture (HR, 0.595; 95% CI, 0.400-0.885; HR, 0.433; 95% CI, 0.327-0.573, respectively)., Conclusions: Compliant and persistent use of bisphosphonate decreases the risk of second hip fracture, in terms of secondary prevention.

Summary: Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs., Introduction: Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples., Methods: A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis., Results: Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta)., Conclusion: Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.

Summary: We evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the Health Insurance Review and Assessment Service (HIRA)., Introduction: Recently, atypical hip fractures in the subtrochanteric region have been reported among patients on bisphosphonate. However, the association between atypical hip fracture and bisphosphonate is controversial. We evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the HIRA., Methods: All new visits or admissions to clinics or hospitals for a typical and atypical hip fractures were recorded nationwide by HIRA using the ICD-10 code classification. Typical and atypical hip fractures were defined as femoral neck/intertrochanteric and subtrochanteric fracture, respectively. Bisphosphonate prescription data were also abstracted from the HIRA database., Results: The absolute number of typical and atypical hip fracture increased during the study period. Although age-adjusted incidence rates of typical hip fractures were stable in men and women, those of atypical hip fractures increased in women. Nationally, the annual numbers of prescriptions of bisphosphonate also increased during the study period., Conclusions: The results of this study suggest a possible causal relationship between bisphosphonate use and the increased incidence of atypical hip fracture in Korea.

Unlabelled: Many diabetic patients with vertebral fractures remain undiagnosed and untreated. We found that more than two-thirds of osteoporotic diabetic women could not be identified for pharmacological treatment according to the NOF guidelines if without radiographic vertebral assessment. This study shows the importance of radiographic vertebral assessment for identifying patients who need treatment for osteoporosis in diabetic women., Introduction: Diagnosis of vertebral fracture (VF) is important for identifying patients who need pharmacologic therapy for osteoporosis. However, many patients with vertebral fractures remain undiagnosed and untreated. This study evaluated the number of patients with VFs who would be unrecognized as candidates for osteoporosis treatments according to the National Osteoporosis Foundation (NOF) Clinician’s Guidelines to the Treatment of Osteoporosis, among postmenopausal diabetic Korean women without spinal imaging., Methods: A total of 873 postmenopausal diabetic women were enrolled. Lateral plain radiographs of the thoracolumbar spine and total hip BMD were obtained. The Fracture Risk Assessment Tool (FRAX®) probability was computed using the algorithm available online at http://www.shef.ac.uk/FRAX (South Korea version). The subjects with and without VFs were classified into candidates for osteoporosis treatment [Tx+by NOF] and not candidates for osteoporosis treatment [Tx−by NOF] according to the NOF pharmacologic treatment guidelines, regardless of the presence of VFs., Results: Forty-six percent of postmenopausal diabetic womenhad morphometric VFs. Among the subjects with morphometric VFs, only 2% of the patients had previously diagnosed VFs by medical doctors. In addition, 73.6% of the patients with VFs were not included in the [Tx+by NOF] group, given the assumption of no radiographic diagnosis of VFs., Conclusions: With regard to increased risk of VFs in postmenopausal Korean women with type 2 diabetes mellitus, radiographic vertebral assessment would be useful for the clinical identification of osteoporosis and fractures.

Summary: Although obesity and osteoporosis are important public health problems, the effect of fat mass on bone mass remains controversial. This study demonstrated that fat mass was inversely related to bone mineral content, and abdominal obesity was significantly associated with bone mineral content independent of total fat mass., Introduction: Obesity and osteoporosis, two disorders of body composition, have become increasingly important public health problems throughout the world. However, the effect of fat mass on bone mass remains controversial. This study investigates the effect of fat mass and regional fat distribution on bone mass within a community-dwelling cohort., Methods: A total of 3,042 subjects (1,284 men, 362 premenopausal women, and 1,396 postmenopausal women) were studied. Fat mass, percent fat mass, lean mass, percent lean mass, and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry., Results: Fat mass and percent fat mass decreased significantly across increasing tertiles of BMC in all three subgroups (men, premenopausal and postmenopausal women). In contrast, lean mass and percent lean mass increased significantly across tertiles of BMC in men, and a similar trend was also identified in postmenopausal women. Interestingly, although correlation analysis showed a positive association between fat mass and BMC (p < 0.05), this association became negative after controlling for age and weight (p < 0.05). Finally, in premenopausal and postmenopausal women, subjects with the lowest waist circumference (WC) had the highest BMC in the higher three quartiles of percent fat mass after adjusting for age and weight (p < 0.05), indicating that abdominal obesity is associated with BMC independent of total fat mass., Conclusion: This study demonstrated that fat mass was inversely related to BMC after removing the mechanical loading effect in Korean men and women. Moreover, abdominal obesity as measured by WC was significantly associated with BMC independent of total fat mass.

We report on electron-spin resonance microscopy (ESRM) providing sub-micron resolution (~700nm) with a high spin concentration sample, i.e. lithium phthalocyanine (LiPc) crystal. For biomedical applications of our ESRM, we have imaged samples containing rat basophilic leukemia (RBL) cells as well as cancerous tissue samples with a resolution of several microns using a water soluble spin probe, Trityl&#95;OX063&#95;d24. Phantom samples with the nitroxide spin label, (15)N PDT, were also imaged to demonstrate that nitroxides, which are commonly used as spin labels, may also be used for ESRM applications. ESRM tissue imaging would therefore be valuable for diagnostic or therapeutic purposes. Also, ESRM can be used to study the motility or the metabolism of cells in various environments. With further modification and/or improvement of imaging probe and spectrometer instrumentation sub-micron biological images should be obtainable, thereby providing a useful tool for various biomedical applications.

This study investigated the effect of intrathecal fentanyl on the dose of propofol during sedation guided by Cerebral State Index monitoring. Seventy patients were randomly assigned to receive either fentanyl 25 microg (n = 35) or normal saline (n = 35) with hyperbaric bupivacaine 12.5 mg for spinal anaesthesia. Propofol was infused to maintain a Cerebral State Index value of 65-75 for 30 min. The propofol infusion time and dose required to reach a Cerebral State Index value of 75 were recorded together with the time required to reach a Cerebral State Index value higher than 90 after cessation of sedation. The onset time for sedation was faster and the recovery time was slower in the fentanyl group compared to those in the saline group (p = 0.018 and 0.027, respectively). The propofol doses required for onset and maintenance of sedation were significantly lower in the fentanyl group compared to those in the control group (p = 0.018 and < 0.001, respectively). In conclusion, adding intrathecal fentanyl 25 microg during spinal anaesthesia significantly reduced the dose of propofol required for sedation and prolonged the subsequent recovery time.

Prolongation of the corrected QT (QTc) interval is associated with various anaesthetic drugs. The QTc prolongation may become more exacerbated during laryngoscopy and intubation, which is possibly caused by sympathetic stimulation. The aim of this study was to investigate the effects of fentanyl on the QTc interval during propofol induction in healthy patients. The patients were randomly allocated to receive either fentanyl (n = 25) or saline (n = 25) before induction. The QTc interval was significantly prolonged immediately after intubation in control group compared to preceding values, but it did not change in the fentanyl group. The number of patients with the prolonged QTc interval exceeding 20 ms immediately after intubation compared to the baseline values was 14 in the control group and seven in the fentanyl group. In conclusion, pretreatment with fentanyl 2 microg x kg(-1) significantly attenuated QTc prolongation associated with laryngoscopy and tracheal intubation during propofol induction.

Stimulation of the sympathetic nervous system associated with tracheal intubation causes corrected QT (QTc) interval prolongation. We postulated that the use of remifentanil during induction of anaesthesia might prevent this. Sixty unpremedicated, ASA grade 1 patients were selected and randomly allocated to receive either saline (group S), remifentanil 0.5 microg x kg(-1) (group R 0.5) or remifentanil 1.0 microg x kg(-1) (group R1.0) 1 min before laryngoscopy. The QTc interval was significantly prolonged immediately following intubation in group S and group R0.5, but it remained stable in group R1.0, compared with the QTc interval just before laryngoscopy. It is concluded that the administration of remifentanil 1.0 microg x kg(-1) before intubation can prevent the prolongation of the QTc interval associated with tracheal intubation during induction of anaesthesia with sevoflurane.

Sulfotransferase 1E1 (SULT1E1) catalyze estrogen into sulfate conjugation and is involved in the metabolism of phytoestrogen. A community-based cross-sectional study was conducted on 397 Korean women, to evaluate the association between genetic polymorphisms of SULT1E1 and bone mineral density (BMD) and the combined effect of the genetic polymorphism and phytoestrogen intake for BMD in Korean women. BMDs of the distal radius and the calcaneus were measured by dual-energy X-ray absorptiometry. Genotypes of SULT1E1 IVS1-447 C>A, IVS4-1653 T>C, and *959 G>A were determined by the 5'-nuclease assay (TaqMan). Phytoestrogen intake was estimated by a food-frequency questionnaire validated against multiple 24-hour recalls. Women with the SULT1E1 *959 GG genotype had a 4.5% lower BMD at the distal radius (P (trend )= 0.05) and a 7.9% lower BMD at the calcaneus compared to those with AA genotype (P (trend) < 0.01), whereas the SULT1E1 IVS1-447 CC genotype and IVS4-1653 TT genotype were not associated with BMD. There was no significant trend of BMD with the numbers of CTG-containing haplotypes, but calcaneal BMDs significantly differed between SULT1E1 CTA-CTA haplotype and CTG-CCA haplotype (P < 0.05). When stratified by SULT1E1 genotype, the correlation between phytoestrogen consumption and BMD at the calcaneus was noteworthy in women with SULT1E1 *959 GG genotype (r = 0.25, P = 0.01) or SULT1E1 IVS 4-1653 TT genotype (r = 0.15, P = 0.02). This trend remained significant only in postmenopausal women (r = 0.36, P = 0.01) after multiple testing was corrected by the false discovery rate method. In conclusion, the genetic polymorphism of SULT1E1 *959 G > A was associated with BMD at the distal radius and calcaneus, and the association between phytoestrogen consumption and calcaneal BMD might be modified by this genetic polymorphism.

Bone morphogenetic proteins (BMPs) play critical roles in osteoblast differentiation. To investigate the association between common single-nucleotide polymorphisms (SNPs) of BMPs and bone mineral density (BMD), a cross-sectional study was conducted in healthy Korean men (n = 237) and women (n = 276) aged 20-39 years. Calcaneus and distal radius BMD were measured by dual energy X-ray absorptiometry. SNPs of BMP2 (-1103C > A, c.584G > A, IVS1-2744A > G, c.893T > A), BMP4 (c.712T > C, IVS1-160C > T), and BMP6 (c.1283C > G, IVS4-6838A > G, IVS5 + 24C > T) were determined using the 5'-nuclease assay. Significant associations were observed between BMP2 c.584G > A, c.893T > A genotypes and male calcaneus as well as female distal radius BMD. Men with the BMP2 c.893 AA genotype had a 16% higher BMD at the calcaneus (P for trend = 0.014), whereas women with this genotype had a 7% lower BMD at the distal radius than the other genotypes (P for trend = 0.010). A significant association was also observed between BMP4 IVS1-160C > T and male calcaneus BMD (P for trend = 0.024). When the association between haplotypes and BMD was investigated, the AAGA haplotype of BMP2 was significantly associated with low bone mass in female distal radius (P for trend = 0.013). These results suggested that one or more SNPs of BMP2 and BMP4 are associated with peripheral BMD in Korean men and women. However, this association is dependent on anatomical sites and gender. Thus, larger studies with complete coverage of SNPs are needed in the future.

To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.

Background: The Laryngeal Tube (LT), (VBM Medizintechnik, Sulz, Germany) is a relatively new supraglottic device for controlling the airway. Arterial carbon dioxide tension (PaCO(2)) can be estimated by monitoring the end-tidal tension of carbon dioxide (PETCO(2)). The relationship between PETCO(2) and PaCO(2) during controlled ventilation via the LT has not been reported., Methods: During general anesthesia, 45 patients were mechanically ventilated using an LT. PETCO(2) and PaCO(2) were measured once PETCO(2) had reached a steady state. The LT was then removed and the trachea intubated using an endotracheal tube (ETT), and the identical ventilatory variables were resumed. Following stabilization, PETCO(2) was again determined and PaCO(2) estimated., Results: The mean PETCO(2) and PaCO(2) values were 4.43 +/- 0.26 kPa and 4.67 +/- 0.32 kPa, respectively, during LT ventilation, and 4.36 +/- 0.23 kPa and 4.61 +/- 0.26 kPa, respectively, during ETT ventilation. Analysis of differences between the PETCO(2) and PaCO(2) values using the Bland and Altman method revealed a bias +/- precision of 0.24 +/- 0.15 kPa for LT and 0.27 +/- 0.15 kPa for ETT. The root mean square error was 0.28 for the LT and 0.30 for the ETT., Conclusion: This study suggests that for healthy adult patients mechanically ventilated via the LT, the PETCO(2) value reflects the PaCO(2) value as closely as when patients are ETT ventilated, allowing capnometry to be used to evaluate the adequacy of ventilation.

A novel intracellular glucosyltransferase (GTase) was isolated from cells of Actinoplanes sp. CKD485-16-acarbose-producing cells. The enzyme was purified by DEAE-cellulose and G75-40 Sephadex chromatography. The molecular mass of the enzyme was estimated to be 62 kDa by SDS-polyacrylamide gel electrophoresis, and its isoelectric point (pI) was pH 4.3. The N-terminal sequence of the GTase consisted of NH(2)-Ser-Val-Pro-Leu-Ser-Leu-Pro-Ala-Glu-Trp. The optimum pH and temperature were 7.5 and 30 degrees C. The enzyme was stable in a pH range of 5.5-9.0 and below 40 degrees C. Enzymatic reactions were performed by incubating the GTase with various substrates. The GTase converted acarbose into component C, maltose into trehalose, and maltooligosaccharides into maltooligosyl trehaloses. The reactions were reversible. Various acarbose analogs were tested as inhibitors against the GTase as a means to suppress component C formation. Valienamine was the most potent, with an IC(50) value of 2.4x10(-3) mM and showed a competitive inhibition mode.

The connexin45 (Cx45) gene was cloned from a mouse genomic Bacterial Artificial Chromosome library. Approximately 8.4 kb of the genomic DNA was sequenced, and the structure of the Cx45 gene was determined. The mouse Cx45 gene is composed of 3 exons, with the entire coding sequence contained within exon III (EMBL Accession Number AJ300716). This structure is unique for the Cx45 gene, since all other members of the connexin family have only two exons. In addition, computer analysis reveals a potential TATA box and two putative AP-1 binding sites in the 5' region of the gene. Sequence alignment with connexin43 indicates substantial homology in the intronic sequences upstream of the 3' exons of the two genes, suggesting that the Cx45 gene is inherently similar to the rest of the connexin family, and that it probably evolved from an ancestor common to the other connexins.

N-benzyloxycarbonyl-L-aspartic acid ethyl ester-D-alanine amide, a derivative of alitame, was synthesized from a eutectic mixture of the substrates N-benzyloxycarbonyl-L-aspartic acid diethyl ester and D-alanine amide using alpha-chymotrypsin. The hydrophilic solvents DMSO and MEA were found to be the best adjuvants for formation of a eutectic substrate mixture. A low eutectic temperature of 27 degrees C was obtained for the substrate mixture containing 9% DMSO, 18% MEA, and 12% water. Under these conditions a conversion yield of 70.3% (mol/mol) was obtained at 37 degrees C. The optimum molar ratio of the acyl acceptor D-alanine amide and the acyl donor N-benzyloxycarbonyl-L-aspartic acid diethyl ester was 1:1.

Abnormalities in mitochondrial DNA(mtDNA) have been implicated in the pathogenesis of diabetes mellitus. We recently reported that decreased mtDNA content precedes the development of diabetes mellitus and is associated with parameters of insulin resistance. In this study, we examined whether there is any relation between mtDNA content and insulin secretion. We compared the mtDNA content of peripheral blood leukocytes with the parameters of insulin secretion measured by hyperglycemic clamp in a group of healthy young men. There were statistically significant correlations between mtDNA content in peripheral blood and fasting plasma insulin (r=-0.43, P<0.05) and C-peptide levels (r=-0.44, P<0.05). MtDNA content also correlated negatively with acute insulin response(r=-0.48, P<0.05), late insulin response (r=-0.50, P<0.05) during hyperglycemic clamp and insulin secretion after glucagon stimulation (r=-0.60, P<0.01). mtDNA content in peripheral blood correlated negatively with homeostasis model (HOMA) insulin resistance (r=-0.45, P<0.05) although it did not correlate with the insulin insensitivity index (M/I) during hyperglycemic clamp. In summary, the mtDNA content of peripheral blood correlated negatively with indices of insulin resistance and insulin secretion in healthy young men. The compensatory response of pancreas beta cells to insulin resistance might contribute in part to increased insulin secretion in these subjects.

Objective: The production of reactive oxygen species is increased in diabetic patients, especially in those will poor glycemic control. We have investigated oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG) as a biomarker., Research Design and Methods: We studied 41 type 2 diabetic patients and compared them with 3 nondiabetic control subjects. Serum 8-OHG concentration was assayed using high-pressure liquid chromatography., Results: The type 2 diabetic patients had significantly higher concentrations of 8-OHG in their serum than the control subjects (5.03 +/- 0.69 vs. 0.96 +/- 0.15 pmol/ml P < 0.01). There was no association between the levels of 8-OHG and HbA1c. We also could not and any correlation between serum 8-OHG levels and age, duration of diabetes, serum lipids, or creatinine or albumin exeretion rate. Creatinine clearance showed marginal correlation with serum 8-OHG levels (P = 0.06). Among the diabetic patients, those with proliferative retinopathy had significantly higher 8-OHG levels than those with nonproliferative retinopathy or without retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced nephropathy (azotemia) were higher than in patients with normoalbuminuria, microalbuminuria, or overt proteinuria., Conclusions: Our findings show that measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA damage. Diabetic patients, especially those with advanced microvascular complications, had significantly higher serum 8-OHG levels; this suggests that such changes may contribute to the development of microvascular complications of diabetes.

Objective: To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD)., Methods: Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20-40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean +/- 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity., Results: The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, -2.2 +/- 0.8 vs. 0.0 +/- 1.0 SDS, p < 0.0001); IGFBP-3, -1.7 +/- 1.2 vs. 0.0 +/- 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20-40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6., Conclusion: Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20-40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD., (Copyright 2002 S. Karger AG, Basel)

Changes in cell life cycle and intracellular structure of Monascus sp. J101 by coculture with Saccharomyces cerevisiae were investigated. Cocultured Monascus cells showed accelerated cell growth and reproduction. Production of asexual and sexual spores was used as an efficient method of cell proliferation. Formation of meiotic (sexual) spores was more frequently observed in the cocultured Monascus cells. The interior structure of a cocultured cell was characterized by increased numbers and sizes of vacuoles. The vacuoles probably serve as repositories for pigment storage. Pigments produced by the cocultured Monascus cells were more hydrophobic than pigments produced by control cells with no coculture.

We have previously indicated that human osteoblasts express a repertoire of cadherins and that perturbation of cadherin-mediated cell-cell interaction reduces bone morphogenetic protein 2 (BMP-2) stimulation of alkaline phosphatase activity. To test whether inhibition of cadherin function interferes with osteoblast function, we expressed a truncated N-cadherin mutant (NCaddeltaC) with dominant negative action in MC3T3-E1 osteoblastic cells. In stably transfected clones, calcium-dependent cell-cell adhesion was decreased by 50%. Analysis of matrix protein expression during a 4-week culture period revealed that bone sialoprotein, osteocalcin, and type I collagen were substantially inhibited with time in culture, whereas osteopontin transiently increased. Basal alkaline phosphatase activity declined in cells expressing NCaddeltaC, relative to control cells, after 3 weeks in culture, and their cell proliferation rate was reduced moderately (17%). Finally, 45Ca uptake, an index of matrix mineralization, was decreased by 35% in NCaddeltaC-expressing cells compared with control cultures after 4 weeks in medium containing ascorbic acid and beta-glycerophosphate. Similarly, BMP-2 stimulation of alkaline phosphatase activity and bone sialoprotein and osteopontin expression also were curtailed in NCaddeltaC cells. Therefore, expression of dominant negative cadherin results in decreased cell-cell adhesion associated with altered bone matrix protein expression and decreased matrix mineralization. Cadherin-mediated cell-cell adhesion is involved in regulating the function of bone-forming cells.

During the fermentation process of Monascus 3101, coculture with Saccharomyces cerevisiae culture filtrate stimulated the formation of reproductive spores, which subsequently resulted in accelerated Monascus cell reproduction and proliferation. Protein kinase C activity was also detected. Chitinase (EC 3.2.1.14), a 120-kDa secretory protein, was purified from the S. cerevisiae culture filtrate as the effector. Monascus cells cocultured with a S. cerevisiae culture filtrate contained approximately four times more total lipids (mainly linoleic and oleic acid) than Monascus cells without coculture. Addition of exogenous fatty acids only contributed to an increase in cell mass. There was no effect on spore formation or pigment production. There were significant changes in patterns and amounts of expressed proteins in cocultured Monascus cells compared to control cells with no coculture.

Non-redundant expressed sequence tags (ESTs) were generated from six different organs at various developmental stages of Chinese cabbage, Brassica rapa L. ssp. pekinensis. Of the 1,295 ESTs, 915 (71%) showed significantly high homology in nucleotide or deduced amino acid sequences with other sequences deposited in databases, while 380 did not show similarity to any sequences. Briefly, 598 ESTs matched with proteins of identified biological function, 177 with hypothetical proteins or non-annotated Arabidopsis genome sequences, and 140 with other ESTs. About 82% of the top-scored matching sequences were from Arabidopsis or Brassica, but overall 558 (43%) ESTs matched with Arabidopsis ESTs at the nucleotide sequence level. This observation strongly supports the idea that gene-expression profiles of Chinese cabbage differ from that of Arabidopsis, despite their genome structures being similar to each other. Moreover, sequence analyses of 21 Brassica ESTs revealed that their primary structure is different from those of corresponding annotated sequences of Arabidopsis genes. Our data suggest that direct prediction of Brassica gene expression pattern based on the information from Arabidopsis genome research has some limitations. Thus, information obtained from the Brassica EST study is useful not only for understanding of unique developmental processes of the plant, but also for the study of Arabidopsis genome structure.

Cadherins, a family of cell-cell adhesion molecules, provide recognition signals that are important for cell sorting and aggregation during tissue development. This study was performed to determine whether distinct cadherin repertoires define tissue-specific lineages during differentiation of immature C3H10T1/2 and C2C12 mesenchymal cells. Both cell lines expressed mRNA for N-cadherin (N-cad), cadherin-11 (C11), and R-cadherin (R-cad). After induction of osteogenesis by recombinant human BMP-2 (rhBMP-2) treatment, steady state N-cad mRNA slightly increased in C3H10T1/2 cells. Likewise, the abundance of C11 mRNA increased in both cell lines, although the changes were more remarkable in C2C12 cells. By contrast, R-cad expression was almost shut off by rhBMP-2. The immature but committed osteoblastic MC3T3-E1 cells exhibited only minor changes in N-cad and C11 mRNA abundance after rhBMP-2 treatment. Whereas adipogenic differentiation was associated with a net decrease of N-cad and C11 expression in C3H10T1/2 cells, induction of myogenesis in C2C12 cells resulted in up-regulation of N-cad, while R-cad mRNA became undetectable in either case. Similarly, the adipocytic 3T3-L1 cells expressed very low levels of all cadherins when fully differentiated. Therefore, the repertoire of cadherins present in undifferentiated mesenchymal cells undergoes distinct changes during transition to mature cell phenotypes. Although neither N-cad nor C11 represent strict tissue-specific markers, the relative abundance of these mesenchymal cadherins defines lineage-specific signatures, perhaps providing recognition signals for aggregation and differentiation of committed precursors., (Copyright 2000 Wiley-Liss, Inc.)

Human osteoblasts express a repertoire of cadherins, including N-cadherin (N-cad), cadherin-11 (C11), and cadherin-4 (C4). We have previously shown that direct cell-cell adhesion via cadherins is critical for BMP-2-induced osteoblast differentiation. In this study, we have analyzed the regulation of cadherin expression in normal human trabecular bone osteoblasts (HOB), and osteoprogenitor marrow stromal cells (BMC), during exposure to dexamethasone, another inducer of human bone cell differentiation. Dexamethasone inhibited the expression of both C11 and N-cad mRNA in both BMC and HOB, although the effect was much more pronounced on N-cad than on C11. This action of the steroid was dose dependent, was maximal at 10(-7) M concentration, and occurred as early as after 1 day of incubation. By contrast, expression of C4 mRNA and protein was strongly induced by dexamethasone in BMC and was stimulated in HOB. This stimulatory effect lasted for at least 2 weeks of incubation. A cadherin inhibitor, HAV-containing decapeptide only partially ( approximately 50%) prevented dexamethasone-induced stimulation of alkaline phosphatase activity by BMC, which instead was not altered by incubation with a neutralizing antibody against C4. Therefore, the pattern of cadherin regulation by dexamethasone radically differs form that observed with BMP-2. Dexamethasone effects on certain osteoblast differentiated features, such as induction of alkaline phosphatase activity are not strictly dependent on cadherin function., (Copyright 2000 Wiley-Liss, Inc.)

Possible methods to minimize the toxic effects of SOx and NOx on the growth of a highly CO2 tolerant and fast-growing microalga, Chlorella sp. KR-1, were investigated. Maintaining the pH of the culturing media at an adequate value was quite important to enhancing the tolerances of the microalgae to SOx and NOx. Controlling the pH by adding an alkaline solution, using a low flow rate of gas fed to the culture, and using a high concentration of inoculating cells were effective methods to maintaining the proper pH of the culture. Controlling the pH was the most effective method but could be applied only for some specific microalgae.

Economical production of cellulase enzyme is key for feasible bio-ethanol production from lignocellulosics using an enzyme-based process. On-site cellulase production can be more feasible with the process of separate hydrolysis and fermentation (SHF) than with simultaneous saccharification and fermentation, since the cost of enzyme is more important and a variety of substrates are available for the SHF process. Cellulase production using various biomass substrates available for SHF, including paper sludge, pretreated wood (steam exploded), and their hydrolysis residues, was investigated in shake flasks and a fermenter for their productivities and titers. Among the newspaper sludge, office paper sludge, and steam-exploded woods treated in various ways, the steam-exploded wood showed the best properties for substrate in cellulase production. The best titer of 4.29 IU/mL was obtained using exploded wood of 2% (w/v) slurry in the shake flask, and the titer with the same substrate was duplicated to about 4.30 IU/mL in a 3.7-L fermenter. Also, the yield of enzyme reached 215 IU/g of substrate or 363 IU/g of cellulose. Despite various pretreatment attempts, newspaper and office paper substrate was inferior to the exploded-wood substrate for cellulase production. However, hydrolysis residues of papers showed quite promising results. The hydrolysis residue of office paper produced 2.48 IU/mL of cellulase in 7 d. Hence, the utilization of hydrolysis residues for cellulase production will be further investigated in the future.

Objectives: To compare the prevalence and metabolic profiles of glucose tolerance categories according to World Health Organization(WHO) and 1997 American Diabetes Association(ADA) fasting criteria for the diagnosis of diabetes mellitus and impaired glucose metabolism in the Korean population., Methods: 2251 subjects without previous history of diabetes, who participated in the Yonchon diabetes epidemiology survey in 1993, were classified according to both criteria. The prevalence of glucose tolerance categories and the agreement across all categories of glucose tolerance were calculated. Metabolic characteristics of different glucose tolerance categories were compared., Results: The prevalence of diabetes and impaired fasting glucose(IFG) according to ADA fasting criteria was similar to those of diabetes and impaired glucose tolerance(IGT) according to WHO criteria, respectively. However, 35.5% of the subjects who were diagnosed as diabetes by WHO criteria were reclassified as either IFG or normal fasting glucose (NFG), and 38.5% of diabetic patients according to ADA fasting criteria were IGT or normal glucose tolerance (NGT) by WHO criteria. Only 31.3% of IGT subjects remained as IFG and 62.1% were reclassified as NFG. Similarly, 69.4% of IFG subjects were NGT by WHO criteria. The agreement between the two criteria was poor (K = 0.31). Discordant diabetes groups had higher WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than concordant non-diabetes group. Non-diabetes(WHO)/diabetes(ADA) group had higher WHR than diabetes (WHO)/non-diabetes(ADA) group. There were no differences in other metabolic characteristics between the two discordant diabetes groups. IGT/NFG and NGT/IFG group showed higher BMI, WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than NGT/NFG group. Metabolic characteristics of IGT/NFG group were not different from those of NGT/IFG group except IGT/NFG subjects were older than NGT/IFG subjects., Conclusion: The agreement between WHO and ADA fasting criteria was poor. ADA fasting criteria can detect new diabetic patients and subjects with impaired glucose metabolism who are not classified as diabetes or IGT by WHO criteria. However, a substantial number of subjects, who may have increased cardiovascular risk and/or increased risk for the development of diabetes and its complication, will be missed when using ADA fasting criteria.

Both qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been implicated in the pathogenesis of diabetes mellitus. It was previously found that decreased mtDNA content preceded the development of diabetes and mtDNA content correlated with the clinical parameters of insulin resistance syndrome, including diastolic blood pressure and waist-hip ratio. These results prompted one to look whether there are correlations between mtDNA content and the biochemical parameters of insulin resistance in non-diabetic subjects. MtDNA content of peripheral blood leukocytes was measured in Korean healthy young men, and this was correlated with various parameters of fuel metabolism at baseline and during euglycemic hyperinsulinemic clamps with indirect calorimetry. MtDNA content in peripheral blood leukocytes did not correlate with insulin sensitivity index or other metabolic variables such as body mass index (BMI), waist-to-hip ratio (WHR) and blood pressure. However, mtDNA content showed a positive significant correlation with fat oxidation rate during euglycemic clamps (r = 0.61, P < 0.05). Changes in fat oxidation rate and carbohydrate oxidation rate during the clamps were significantly correlated with mtDNA content (r = 0.65, P < 0.05, r = -0.65, P < 0.05, respectively). These results suggest that mtDNA content in peripheral blood may not correlate with insulin resistance per se but with some aspect of insulin resistance in healthy young men.

Glucose intolerance is often found in patients with hyperthyroidism, but the pathogenetic mechanisms are not fully understood. Since lipolysis is increased in hyperthyroidism, elevated plasma nonesterified fatty acids (NEFAs) may contribute to abnormal glucose metabolism in hyperthyroidism. The aim of this study was to investigate whether decreasing the plasma NEFA level with acipimox can affect glucose metabolism in hyperthyroidism. We performed an intravenous glucose tolerance test (IVGTT) with acipimox 250 mg or placebo in six untreated hyperthyroid men and six age- and body mass index (BMI)-matched controls. Fasting plasma NEFA levels were significantly higher in the hyperthyroid patients versus the controls (997.0 +/- 303.4 v290.5 +/- 169.1 micromol/L, P < .001). Plasma NEFAs decreased rapidly with acipimox treatment in both controls and hyperthyroid patients. In the controls, the glucose disappearance constant (K(G)) was not different for acipimox treatment versus placebo (2.18 +/- 0.62 v 2.42 +/- 1.00% x min(-1)). In hyperthyroid patients, acipimox treatment increased the K(G) significantly compared with placebo treatment (2.44 +/- 0.84 v 1.58 +/- 0.37% x min(-1), P < .05). Changes in K(G) values with acipimox treatment were inversely correlated with changes in plasma NEFA levels (r = -.65, P < .05). Acipimox treatment increased the acute insulin response (AIR) in hyperthyroid patients (943 +/- 381 v 698 +/- 279 microU/mL x min, P < .05), whereas it did not change the AIR in controls. Changes in the AIR with acipimox treatment correlated significantly with changes in the K(G) (r = .70, P < .05). There was a weak correlation between changes in the AIR with acipimox treatment and changes in plasma NEFA levels (r = -.55, P = .06). In summary, decreasing the plasma NEFA level with acipimox in hyperthyroid patients increases both the K(G) and AIR during an IVGTT. These findings suggest that the abnormal glucose metabolism in hyperthyroidism could be attributed, at least in part, to the increase of plasma NEFA.

Objectives: The changes in circulating IGF components after the menopause and the potential role of new markers of bone turnover and circulating IGF components in predicting bone mass in postmenopausal women are still controversial and the relationship between these two systems has not been investigated. The aims of this study were to investigate the changes in circulating IGF components after the menopause, to evaluate whether new markers of bone turnover and circulating IGF components reflect bone mass in postmenopausal women under the age of 60 and to study the relationship between these two systems., Design, Patients and Measurements: Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, osteocalcin (OST), bone specific alkaline phosphatase (BAP), urinary deoxypyridinoline (DPYD) and N-telopeptide of type I collagen (NTX) were measured in 31 premenopausal women aged 31-43 and 65 postmenopausal women aged 47-60: this latter group comprised 30 normal healthy women and 35 osteoporotic women., Results: Compared with premenopausal women or normal postmenopausal women, serum IGF-1 and IGFBP-3 levels were significantly lower in osteoporotic postmenopausal women while no significant differences in serum levels of IGF-II, IGFBP-1 and IGFBP-2 were observed. The correlations between bone turnover markers and circulating IGF components (except between serum BAP and IGF-II), and between bone turnover markers and bone mineral density (BMD) in postmenopausal women were not significant. However, serum IGF-I and IGFBP-3 correlated positively with BMD of the lumbar spine and/or Ward's triangle even if age, BMI and menopause duration were taken into account in a multiple regression analysis model., Conclusions: Circulating IGF-I and IGFBP-3 may be involved in the mechanism of bone loss in postmenopausal women under the age of 60. They may also provide indirect information on the current bone microenvironment different from that provided by new markers of bone turnover.

Objective: Previous studies have shown that the rapid ACTH stimulation test using a low dose of 1 microg is more sensitive than that using 250 microg ACTH for detecting subtle cases of adrenal insufficiency. However, there are controversies for the reproducibility of the 1 microg-test. To evaluate the reproducibility of the 1 microg-test, we assessed both day-to-day and diurnal variations of cortisol responses to 1 microg ACTH injection. In addition, optimum sampling time for the 1 microg-test was also determined., Subjects: AND DESIGN Eight healthy volunteers and five patients with secondary adrenal insufficiency were recruited. Healthy subjects were given 1 microg ACTH 3 times in the morning (0800 h) and 2 times in the afternoon (1600 h). Patients with adrenal insufficiency had 2-tests in the morning and 2 in the afternoon. Serum cortisol levels were measured every 10 minutes for 1 h after the injection., Results: In healthy subjects, basal and peak serum cortisol levels were significantly higher in the morning (P < 0.05), whereas maximum cortisol increments were higher in the afternoon (P < 0.001). In patients with adrenal insufficiency, basal and peak serum cortisol levels in the morning were not different from corresponding values in the afternoon. Intra-individual coefficient of variation (CV) of peak serum cortisol response to 1 microg ACTH ranged from 3.0 to 16.4% in healthy subjects and 10.0-34. 4% in patients. Also, there was a significant correlation between peak morning or afternoon cortisol levels after 1 microg ACTH injection given in different days in both healthy subjects and patients. Twenty-six of the 40 studies in healthy subjects showed peak response at 20 minutes, while nine showed it at 30 minutes Using the data acquired at 20 and 30 minutes, all 40 studies in healthy subjects showed normal results while none of 20 studies in patients was normal., Conclusions: We conclude that the cortisol response to 1 microg ACTH stimulation was reproducible in both healthy subjects and patients with secondary adrenal insufficiency. In order to assess adrenal function more accurately with the 1 microg ACTH stimulation test, serum cortisol should be measured before and 20 and 30 minutes after ACTH injection.

Ethanol production from concentrated oak wood hydrolysate was carried out to obtain a high ethanol concentration and a high ethanol yield. The effect of added inhibitory compounds, which are typically produced in the pretreatment step of steam-explosion on ethanol fermentation, was also examined. p-Hydroxybenzoic aldehyde, a lignin-degradation product, was the most inhibitory compound tested in this study. Compounds with additional methyl groups had reduced toxicity and the aromatic acids were less toxic than the corresponding aldehydes. The lignin-degradation products were more inhibitory than the sugar-derived products, such as furfural and 5-hydroxymethylfurfural (HMF). Adaptation of yeast cells to the wood hydrolysate and detoxification methods, such as using charcoal and overlime, had some beneficial effects on ethanol production using the concentrated wood hydrolysate. After treatment with charcoal and low-temperature sterilization, the yeast cells could utilize the concentrated wood hydrolysate with 170 as well as 140 g/L glucose, and produce 69.9 and 74.2 g/L ethanol, respectively, with a yield of 0.46-0.48 g ethanol/g glucose. In contrast, the cells could not completely utilize untreated wood hydrolysate with 100 g/L glucose. Low-temperature sterilization, with or without charcoal treatment, was very effective for ethanol production when highly concentrated wood hydrolysates were used. Low-temperature sterilization has advantages over traditional detoxification methods, such as using overlime, ion exchange, and charcoal, because of the reduction in the total cost of ethanol production.