Benefits of lumican on human bone health: clinical evidence using bone marrow aspirates

Background/Aims@#Lumican, a small leucine-rich proteoglycan, has shown osteoprotective effects by synchronously stimulating bone formation and suppressing bone resorption. To clarify the role of lumican in human bone metabolism, the association between lumican concentrations and osteoporosis-related phenotypes was evaluated using bone marrow (BM) samples directly reflecting local microenvironments. @*Methods@#BM aspirates were obtained from 77 patients during hip surgery for either fragility hip fractures (HF) (n = 29) or osteoarthritis (n = 48) and centrifuged. Concentrations of lumican and biochemical bone markers in BM supernatants were measured using enzyme linked immunosorbent assays. @*Results@#After considering confounders, lumican concentrations in BM supernatants were 16.9% lower in patients with HF than in controls, with each increase in the standard deviation of lumican concentration being associated with a 61% lower likelihood of HF. The odds ratios for HF decreased linearly with increasing lumican tertiles in BM, with the odds of having fragility HF markedly lower in participants in the highest than in the lowest lumican tertile. Higher lumican level correlated significantly with higher femur neck bone mineral density and higher bone-specific alkaline phosphatase levels, but not with tartrate-resistant acid phosphatase 5b concentrations, in BM supernatants. @*Conclusions@#These data clinically validate previous in vitro and animal experiments showing the beneficial roles of lumican for bone homeostasis and suggest that lumican may contribute to a reduction in fracture risk in humans mainly through its stimulation of bone formation.

Decreased Serum Level of Sclerostin in Older Adults with Sarcopenia

Background@#Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia. @*Methods@#Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay. @*Results@#The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025). @*Conclusion@#Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor

Background@#Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research. @*Results@#Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone. @*Conclusion@#These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults

Background@#The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline. @*Results@#Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index. @*Conclusion@#Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor

Background@#Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research. @*Results@#Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone. @*Conclusion@#These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults

Background@#The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline. @*Results@#Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index. @*Conclusion@#Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures

In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.

Seasonal Variation of Drug Prescription Rate for Overactive Bladder in Men Based on National Health Insurance Claims Data, 2012–2016 / 대한배뇨장애요실금학회지

Purpose@#Overactive bladder (OAB) symptoms might be affected by weather, but only a few clinical studies have investigated this issue. We investigated seasonal variations in OAB-drug prescription rate (DPR) in men using nationwide claims data in Korea. @*Methods@#A total of 2,824,140 men aged over 18 years were included from the Health Insurance Review and Assessment service – National Patient Sample data between 2012 and 2016. Depending on the monthly average temperature, the seasons were divided into 3 groups, namely, hot (June, July, August, and September), intermediate (April, May, October, and November), and cold (January, February, March, and December) seasons. OAB-DPR was estimated using the claims data, and differences in its rate were examined among the 3 seasonal groups. @*Results@#The overall OAB-DPR was 1.97% (55,574 of 2,824,140). The OAB-DPR were 0.38%, 0.63%, 0.92%, 1.74%, 4.18%, 7.55%, and 9.69% in the age groups of under 30, 30s, 40s, 50s, 60s, 70s, and over 80 years, respectively; thus, the prescription rate increased with age (P<0.001), with a steeper increase after 60 years of age. OAB-DPR was 1.02% in the hot season, 1.19% in the intermediate season, and 1.27% in the cold season, with significant differences among the 3 seasonal groups (P<0.001). These seasonal variations persisted in the subgroup analysis in each age decade (P<0.001). @*Conclusions@#OAB-DPR varied with seasons and was significantly higher in the cold season than in the hot season, suggesting that cold weather may affect development and aggravation of OAB symptoms in men.

The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures

In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.

The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures

Nutrition Diagnostic Analysis for Nutrition Care Process Model in Adults of a Health Screening & Promotion Center / 대한지역사회영양학회지

OBJECTIVES: This study was performed to examine nutrition problems and causes/contributing risk factors. METHODS: This study was conducted using data 1,863 adults visited Asan health screening & promotion center located in Seoul, Korea during May to June of 2013. We used Nutrition Care Process Model developed by the International Dietetics & Nutrition Terminology (IDNT). RESULTS: The most frequent nutrition problem in male subjects was excessive alcohol intake. Men in fifties showed the highest rate of excessive alcohol intake among the age groups examined (22.4%). By comparison, the most frequent nutrition problem in women was inadequate protein intake. Women in fifties exhibited the highest rate of inadequate protein intake (22.5%). The most common contributing factors for these observations were a low preference for dairy products followed by high preference for alcohol and a deficit in food-and nutrition-related knowledge, regardless of the sex and age. The most common nutrition problem observed among the group diagnosed with hyperglycemia or hypertriglyceridemia or hyperuricemia or fatty liver was excessive alcohol intake (p<0.001), whereas the group diagnosed with hyperglycemia or hypercholesterolemia showed significantly higher rate of inappropriate intake of carbohydrate (fructose) compared to the group not diagnosed with such disease conditions (p<0.05). The group diagnosed with hypercholesterolemia, hyperuricemia and fatty liver showed significantly higher occurrence of inappropriate intake of fat (saturated fat) than the group free of such diseases (p< 0.001). The osteopenia group showed higher rate of inadequate protein intake (p<0.001) and the fatty liver group with excessive energy intake (p<0.001). Overall, the results suggest that there is a significant relationship between nutrition problems and health conditions found in groups diagnosed with a diverse array of medical conditions. CONCLUSIONS: Therefore, we strongly suggest that dieticians should implement nutrition interventions with people visiting health screening & promotion center based on nutrition problems and the contributing factors diagnosed by dietitions in order to prevent chronic diseases in this population.

Lipid peroxidation and total antioxidant ability in venous plasma and amniotic fluid of pregnant women with preterm premature rupture of membranes / 대한산부인과학회지

OBJECTIVE: To evaluate their roles in the pathophysiology of preterm premature rupture of membranes (PPROM), we checked interleukin (IL)-6, lipid peroxide, oxygen-radical absorbance capacity (ORAC) and antioxidant vitamin in the venous plasma and amniotic fluid of women with PPROM. METHODS: Venous plasma and amniotic fluid was taken from 20 normal pregnant women and 20 PPROM pregnancy women. IL-6 levels was determined by enzyme-linked immunosorbent assay. Lipid peroxide levels were measured by thiobarbituric acid reaction. The ORAC levels and the antioxidant levels were measured by Cao's method and by high performance liquid chromatography. RESULTS: The IL-6 levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values/lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ascorbic acid levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.05, P<0.01). CONCLUSION: This result suggest that the increased inflammatory bioactivity, increased lipid peroxidation and decreased antioxidant activity may be involved in the pathophysiology of PPROM. Low levels of ascorbic acid appears to be an important determinant of PPROM.

Interleukin-6, tumor necrosis factor-alpha, and antioxidant levels in the umbilical venous plasma of preeclampsia / 대한산부인과학회지

OBJECTIVE: Our purpose was to investigate Interleukin-6 (IL-6), tumor necrotic factor-alpha (TNF-alpha), lipid peroxide levels, oxygen-radical absorbance capacity (ORAC), and antioxidant levels in umbilical venous blood plasma and to evaluate the roles of them in the pathophysiology of preeclampsia. STUDY DESIGN: Samples of umbilical venous plasma were obtained from 20 normal and 20 preeclamptic women between 33 and 40 weeks gestation. IL-6 and TNF-alpha was assayed by an enzyme-linked immunoassay. Lipid peroxide levels were measured by thiobarbituric acid reaction. The ORAC values were measured by Cao's method. Ascorbic acid, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. RESULTS: There was no significant differences of IL-6 levels in umbilical venous plasma between women with normal and preeclampsia (2.79+/-0.21 vs. 2.94+/-0.17 ng/ml). TNF-alpha levels in umbilical venous plasma of women with preeclampsia were significantly higher than that of women with preeclampsia (3.04+/-0.01 vs. 1.40+/-0.01 ng/ml, p<0.01). Lipid peroxide levels in umbilical venous plasma of women with preeclampsia were significantly higher than that of women with normal pregnancy (7.32+/-0.09 vs. 5.18+/-0.14, p<0.01). The ORAC values in umbilical venous plasma of women with preeclampsia were significantly lower than that of women with normal pregnancy (12,836.5+/-249.4 vs. 10,490.2+/-276.9 U/ml, p<0.05). Ascorbic acid levels in umbilical venous plasma of women with preeclampsia were significantly lower than those of women with normal pregnancy (320.2+/-48.5 vs. 538.5+/-68.2 nmol/ml, p<0.05). CONCLUSION: The above results in umbilical venous plasma suggest that the imbalance of lipid peroxidation and antioxidant activity in placenta is involved in the pathophysiology of preeclampsia. Increased TNF-alpha in the umbilical venous plasma showed inflammatory reaction in the placenta would be one of the cause of preclampsia. An antioxidant vitamin, ascorbic acid, may act an important antioxidant factor in preeclampsia.

The accuracy of frozen section in the diagnosis of ovarian tumors / 부인종양

OBJECTIVE: As frozen sections play the role of determining the method or scope of operation for ovarian tumors, the present study examined the accuracy, limitations and clinical utility of frozen sections. METHODS: Among 1583 cases of ovarian tumor surgery conducted during the period from January 1999 to September 2005, 372 for which frozen sections were sent to the Department of Pathology were analyzed through comparison between their frozen section diagnosis and final histopathological diagnosis. RESULTS: Among the ovarian tumor cases, the accuracy of frozen section diagnosis was 91.1% and its sensitive to final diagnosis was highest as 96.0% for benign tumors, and 85.7% for malignant tumors, and as low as 62.9% for borderline?tumors (p<0.01). The positive predictive value was 87.1% for malignant tumors, 68.8% for borderline tumors, and 94.6% for benign tumors. Among the 33 cases for which frozen section did not agree with final diagnosis, 15 cases were false positive and 18 cases were false negative. Among them, 14 cases were mucinous tumors (15.4%, 14/91), showing difficulty in diagnosis compared to non-mucinous tumors (6.8%, 19/281) (p=0.018). CONCLUSION: Despite its limitations, frozen section is a very useful method of high accuracy in diagnosing ovarian tumors. Thus, gynecologists and pathologists need to make efforts to understand the limitations and problems of frozen section, which is not highly sensitive to borderline tumors and mucinous tumors, and to make accurate diagnosis.

Significance of morphologic score and vascular index in the diagnosis of ovarian malignancy using ultrasonography / 대한산부인과학회지

OBJECTIVE: The aim of this study was to know whether we can distinguish benign from malignant ovarian tumors according to morphologic scoring system (MS), blood flow characteristics (Resistance index (RI), Pulsatility index (PI)) using color doppler sonography and a combination of both in patients undergoing laparotomy or laparoscopy for a clinically diagnosed ovarian mass. METHODS: From January 2001 to December 2003, 99 patients with ovarian tumors scheduled for laparotomy or laparoscopy were studied at our institute. Ultrasound was carried out to study the ovarian morphology followed by color doppler sonography. A score of > or =9 on MS, a PI or =9 on MS as indicative of malignancy was associated with the following statistical parameters: sensitivity 69.6%, specificity 69.8%, positive predictive value (PPV) 75.0%, negative predictive value (NPV) 63.8%. A mean score of malignant tumor (9.8+/-2.64) is significantly higher than that of benign tumor (7.5+/-2.44). This was statistically significant (p[t]<0.05). A resistance index (RI) < or =0.4 was associated with sensitivity 19.6%, specificity 97.6%, PPV 91.6%, NPV 48.2%. A pulsatility index (PI) < or =1.0 was associated with sensitivity 44.6%, specificity 81.3%, PPV 75.7%, NPV 53.0%. A mean of RI in malignancy (0.64+/-0.277) is lower than that of RI in benign tumor (0.79+/-0.299). A mean of PI in malignancy (1.34+/-0.982) is lower than that of PI in benign tumor (2.06+/-1.310). These was statistically significant (p[t]<0.05). The addition of RI or PI to MS did not improve the accuracy in predicting ovarian malignancy. CONCLUSION: Although RI or PI achieved better specificity and PPV compared to MS, the addition of RI or PI to MS did not increase its accuracy in the discrimination between benign and malignant ovarian tumors.