Obesity, whose prevalence is increasing rapidly worldwide, is recognized as a risk factor for diabetes, cardiovascular disease, liver disease, and renal disease. To investigate metabolic changes in the urine of a rat model of obesity induced by a high-fat diet (HFD), rats were divided into the following four groups based on the diet type and degree of weight gain: normal-diet (ND) low gainers, ND high gainers, HFD low gainers, and HFD high gainers. Biochemical analyses of visceral fat-pad weight, plasma, and liver tissues were performed. The (1)H-nuclear magnetic resonance ((1)H-NMR) spectra of urine were analyzed using multivariate statistical analysis to identify the separation of the groups. It was observed that the metabolic profile of urine obtained by (1)H-NMR-spectroscopy-based metabolomic analysis differed between ND low gainers and ND high gainers even though these animals consumed the same normal diet. Several key metabolites in urine, such as betaine, taurine, acetone/acetoacetate, phenylacetylglycine, pyruvate, lactate, and citrate contributed to the classification of these two groups. The metabolic profile of urine also differed between ND low gainers and HFD high gainers, which consumed the different diet and showed a different weight gain. This study has identified features of urine metabolites in various groups and demonstrated the reliability of an NMR-based metabolomics approach to investigate the effects of the diet and the physical constitution on obesity.

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We investigated the prevalence and risk factors of vertebral fractures in Korea. In a community-based prospective epidemiology study, 1,155 men and 1,529 women (mean age 59 years, range 43-74) were recruited from Ansung, a rural Korean community. Prevalent vertebral fractures were identified on the lateral spinal radiographs at T11 to L4 using vertebral morphometry. Bone mineral density (BMD) was measured at the lumbar spine, femur neck and total hip. Of the 2,684 subjects, 137 (11.9%) men and 227 (14.8%) women had vertebral fractures and the standardized prevalence for vertebral fractures using the age distribution of Korean population was 8.8% in men and 12.6% in women. In univariate analysis, older age, low hip circumference, low BMD, low income and education levels in both sexes, previous history of fracture in men, high waist-to-hip circumference ratio, postmenopausal status, longer duration since menopause, and higher number of pregnancies and deliveries in women were associated with an increased risk of vertebral fractures. However, after adjusting for age, only low BMD in both sexes and a previous history of fracture in men were significantly associated with an increased risk of vertebral fractures. Vertebral fractures are prevalent in Korea as in other countries. Older age, low BMD and a previous history of fracture are significant risk factors for vertebral fractures.

Objectives:The usefulness of a malleable penile prosthesis was evaluated in patients with spinal cord injury (SCI) by investigating the complications and the patients' satisfaction. Methods: A total of 48 patients with a SCI, who underwent malleable penile prosthesis (AMS 600) insertion from 1990 to 2004 were evaluated by reviewing the patients' medical records and interviewing them via questionnaires. The mean patients age was 58.9 years, and the mean follow-up period was 11.7 years. In 23 patients, penile prosthesis implantation was carried out to improve urinary management and to treat erectile dysfunction (ED). Results: Complications occurred in eight patients (16.7%). Wound infections in four (8.3%). Two patients were treated with conservative management, and two were managed through prostheses removal. Other complications were erosion in two patients (4.2%), uncontrolled penile pain owing to excessive prosthesis length in one patient (2.1%), and supersonic transporter (SST) deformity in one patient (2.1%). The overall patient satisfaction rate was 79.2%. The dissatisfaction was mainly due to the complications that resulted in the removal of the prosthesis, or partner's unnatural sensation. All of the prostheses that were implanted in the patients for the improvement of their urinary management gave them the benefit of convenient urinary management, except for two patients, whose prostheses were removed. Conclusions: The insertion of malleable penile prostheses in patients with SCI is associated with low complication rates and good patient satisfaction. It is therefore still an attractive option.

Objectives:To determine whether detection of prostate stem cell antigen (PSCA) expression has potential for molecular staging in prostate cancer (PCa), we examined the relationship between established prognostic factors, biochemical recurrence (BCR) and PSCA expression. Methods: This study was comprised of 66 patients who underwent radical prostatectomy for the treatment of PCa. We employed reverse transcriptase-polymerase chain reaction (RT-PCR) to detect PSCA mRNA-bearing cells in peripheral blood , and used immunohistochemical (IHC) techniques to identify PSCA protein expression in microarrayed tissue. Results: PSCA-mRNA was detected in the peripheral blood of nine (13.6%) patients by RT-PCR. Whereas 3.2% of patients with low-grade disease were PSCA positive, 22.9% of patients with high-grade disease were PSCA positive (P = 0.030). There was also a significant relationship of RT-PCR PSCA positivity to whether or not the tumor was confined to the prostate. Whereas only 6.8% of patients with prostate-confined disease were RT-PCR PSCA positive, 27.3% of extraprostatic diseases were RT-PCR PSCA positive (P = 0.022). IHC studies of tumor tissue microarrays demonstrated that PSCA expression intensity was related to both extraprostatic extension (P = 0.014) and positive surgical margin (P = 0.053). Whereas 23.8% of prostate-confined diseases were high intensity, 54.5% of extraprostatic diseases were high intensity. BCR developed in seven patients (10.6%) during the follow-up period (median, 16.2 months; range, 9-25 months). Prognostic factors increasing the risk of BCR included: seminal vesicle invasion (P = 0.004), extraprostatic disease (P = 0.019), lymphovascular emboli (P = 0.036) and RT-PCR PSCA positivity (P = 0.004) in univariate analysis. Conclusions: We were able to detect PSCA mRNA-bearing cells in peripheral blood by RT-PCR, and also identify PSCA protein expression in tumors by IHC analysis of tissue microarrays. RT-PCR PSCA positivity in peripheral blood may be a potential modality for molecular staging of PCa.

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We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.

Secretagogin (SCGN), a hexa EF-hand calcium binding protein, plays key roles in insulin secretion in pancreatic β-cells. It is not yet understood how the binding of Ca2+ to human SCGN (hSCGN) promotes secretion. Here we have addressed this question, using mass spectrometry combined with a disulfide searching algorithm DBond. We found that the binding of Ca2+ to hSCGN promotes the dimerization of hSCGN via the formation of a Cys193-Cys193 disulfide bond. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics studies revealed that Ca2+ binding to the EF-hands of hSCGN induces significant structural changes that affect the solvent exposure of N-terminal region, and hence the redox sensitivity of the Cys193 residue. These redox sensitivity changes were confirmed using biotinylated methyl-3-nitro-4-(piperidin-1-ylsulfonyl) benzoate (NPSB-B), a chemical probe that specifically labels reactive cysteine sulfhydryls. Furthermore, we found that wild type hSCGN overexpression promotes insulin secretion in pancreatic β cells, while C193S-hSCGN inhibits it. These findings suggest that insulin secretion in pancreatic cells is regulated by Ca2+ and ROS signaling through Ca2+-induced structural changes promoting dimerization of hSCGN.