Metabolic profiling of charged metabolites in association with menopausal status in Japanese community-dwelling midlife women: Tsuruoka Metabolomic Cohort Study.

BACKGROUND: Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. METHODS: The participants were 1193 female residents aged 40-60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. RESULTS: Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. CONCLUSION: Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

Antibiotics Improve the Treatment Efficacy of Oxaliplatin-Based but Not Irinotecan-Based Therapy in Advanced Colorectal Cancer Patients.

BACKGROUND: Oxaliplatin and irinotecan are generally used to treat advanced colorectal cancer (CRC) patients. Antibiotics improve the cytotoxicity of oxaliplatin but not irinotecan in a colon cancer cell line in vitro. This study retrospectively assessed whether antibiotics improve the treatment efficacy of oxaliplatin- but not irinotecan-based therapy in advanced CRC patients. Patients and Methods. The medical records of 220 advanced CRC patients who underwent oxaliplatin- or irinotecan-based therapy were retrospectively reviewed. The oxaliplatin and irinotecan groups were further divided into antibiotic-treated (group 1) and antibiotic-untreated (group 2) subgroups. RESULTS: In oxaliplatin groups 1 and 2, the response rate (RR) was 58.2% and 30.2%, while the disease control rate (DCR) was 92.5% and 64.2%, respectively; the median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI) = 7.5-12.2) and 7.0 months (95% CI = 17.0-26.0), respectively, and the median overall survival (OS) was 23.8 months (95% CI = 5.1-9.1) and 17.4 months (95% CI = 13.1-24.9), respectively. In irinotecan groups 1 and 2, the RR was 17.8% and 20.0%, while the DCR was 75.6% and 69.1%, respectively; the median PFS was 8.2 months (95% CI = 6.2-12.7) and 7.9 months (95% CI = 12.0-23.0), respectively, and the median OS was 16.8 months (95% CI = 5.9-10.6) and 13.1 months (95% CI = 10.4-23.7), respectively. CONCLUSION: To improve the treatment efficacy of oxaliplatin-based therapy in advanced CRC patients, adding antibiotics is a potential therapeutic option.

Utility of the luminance standard deviation to quantify magnetic resonance imaging motion artifact induced by tongue movement.

Clear magnetic resonance imaging (MRI) is required to diagnose tongue cancer. However, the absence of occlusal support may cause tongue movements which are known to introduce artifacts on the MR image. This pilot study compared the manifest of artifacts from the tongue at rest and during motion using luminance standard deviation (LSD) to quantify the artifacts, in dentulous subjects. Participants were ten dentulous participants (5 males, 5 females; age 31.50 ± 8.38 years) with occlusal support. MRI was conducted with the tongue at rest and during lateral movement. The LSD was measured in the regions of interest (ROI) in the axial and sagittal planes. Tongue movement evoked unclear MR images, compared with the images taken at rest. Statistical analysis revealed that the LSD significantly differed between the tongue at rest and in motion in the axial (P = 0.004) and sagittal planes (ROI-A: P = 0.002, ROI-P: P = 0.006). These findings suggest that tongue movement introduces motion artifact and the LSD responds quantitatively to the magnitude of artifacts. Future studies will evaluate whether a prosthetic device used to provide occlusive support can decrease these artifacts when analyzed using LSD.

Metabolic Profiling of Total Physical Activity and Sedentary Behavior in Community-Dwelling Men.

OBJECTIVE: Physical activity is known to be preventive against various non-communicable diseases. We investigated the relationship between daily physical activity level and plasma metabolites using a targeted metabolomics approach in a population-based study. METHODS: A total of 1,193 participants (male, aged 35 to 74 years) with fasting blood samples were selected from the baseline survey of a cohort study. Information on daily total physical activity, classified into four levels by quartile of metabolic equivalent scores, and sedentary behavior, defined as hours of sitting per day, was collected through a self-administered questionnaire. Plasma metabolite concentrations were quantified by capillary electrophoresis mass spectrometry method. We performed linear regression analysis models with multivariable adjustment and corrected p-values for multiple testing in the original population (n = 808). The robustness of the results was confirmed by replication analysis in a separate population (n = 385) created by random allocation. RESULTS: Higher levels of total physical activity were associated with various metabolite concentrations, including lower concentrations of amino acids and their derivatives, and higher concentrations of pipecolate (FDR p <0.05 in original population). The findings persisted after adjustment for age, body mass index, smoking, alcohol intake, and energy intake. Isoleucine, leucine, valine, 4-methyl-2-oxoisopentanoate, 2-oxoisopentanoate, alanine, and proline concentrations were lower with a shorter sitting time. CONCLUSIONS: Physical activity is related to various plasma metabolites, including known biomarkers for future insulin resistance or type 2 diabetes. These metabolites might potentially play a key role in the protective effects of higher physical activity and/or less sedentary behavior on non-communicable diseases.

A pancreatic abscess 7 years after a pancreatojejunostomy for calcifying chronic pancreatitis.

We present herein a case of a 75-year-old Japanese man who had developed a pancreatic abscess 7 years after a longitudinal pancreatojejunostomy for chronic pancreatitis. The patient, a heavy drinker of alcohol, underwent surgical decompression of a ductal obstruction to relieve persistent abdominal pain due to severely calcifying chronic pancreatitis. After the surgery, he stopped drinking alcohol and was treated with insulin to control secondary diabetes mellitus. Thereafter, his symptoms disappeared. Seven years after the surgery, however, he was hospitalized due to obstructive jaundice, high-grade fever, and right hypochondria pain. Ultrasound and computed tomographic scans of the abdomen both disclosed a cystic mass, approximately 6 cm in size, in the pancreatic head. Magnetic resonance imaging strongly suggested a pancreatic abscess with necrotic fluid and debris. First, percutaneous transhepatic cholangiodrainage (PTCD) was done to treat the progressively obstructive jaundice. Subsequently, fine-needle aspiration of the pancreatic abscess was performed under ultrasound guidance. Enterococcus avium and Klebsiella oxytoca were revealed by culture of abscess aspirates. He was successfully cured by treatment with both appropriate antibiotic and continuous PTCD for the obstructive jaundice.