A validated simple LC-MS/MS method for quantifying trimethylamine N-oxide (TMAO) using a surrogate matrix and its clinical application

Trimethylamine N-oxide (TMAO) is a small molecular amine oxide generated from dietary choline and carnitine through intestinal microbial metabolism. Recently, TMAO has attracted much public attention as its role in disease progression has been proven in many clinical studies. The plasma concentration of TMAO in humans was found to be positively associated with the increased risk of many diseases including cardiovascular diseases and chronic kidney diseases. To achieve accurate and sensitive quantitation of TMAO for clinical applications, we established and validated a simple quantitative method using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. We constructed an eight-point calibration curve in an artificial surrogate matrix instead of the commonly used biological matrices to avoid interference from the endogenous TMAO. The calibration curve showed excellent linearity in the range of 1 to 5,000 ng/mL, with a correlation coefficient (R2 ) higher than 0.996 in each validation batch. Moreover, both the intra-day and inter-day assays achieved satisfactory precision and accuracy results ranging from 1.65–7.15% and 96.36–111.43%, respectively. Further, this method was cross-validated using a human plasma matrix and applied to a clinical pharmacology study. Overall, these results demonstrate that the developed quantitation method is applicable in clinical research for monitoring disease progression and evaluating drug effects.

Comparison of Nutritional Status of the Daejeon Metropolitan Citizens by Frequency of Eating Out

This study aims at investigating the health and nutritional status of the adults according to frequency of eating out. One day food intake data were collected by 24 hr recall dietary survey and body size, blood pressure and some blood lipids and other constituents were measured on 137 Daejeon metropolitan citizens 20 yrs old and above who visited Chungnam National University Hospital for physical examination during the period of December 6, to December 15, 2008. The frequency of eating out were categorized into four levels: less than once a week, once a week, 2-3 times a week, 4 times a week and above. Body mass Index, waist circumference, blood pressure, blood lipid, blood glucose, GPT and GOT did not showed any significant difference according to the frequency of eating out of the subjects. Though, systolic blood pressures and serum levels of total cholesterol and LDL-cholesterol showed a little tendency to be high in the subjects eating out 2-3 times a week. In the contrary, serum triglyceride level tended to be low in the same group. The subjects eating out 4 times a week and over took more total protein, animal protein, animal fat, phosphorus and vitamin B2 than any other group. Also protein energy ratio was the highest in the group eating out 4 times a week and above and they took more animal food group, other food group, beverages . teas and alcohols than other groups eating out. These results showed that higher frequency of eating out leads to higher intake of protein, fat, phosphorus, animal food groups and other food groups (oils, beverages, seasonings) and to lower intake of vitamin C and plant food groups. It, thus, suggested that the strategy for restaurant business is required to provide the menu substituted animal food by more plant food.

The Clinical Characteristics According to the Risk Factors of Idiopathic Nonhemolytic Hyperbilirubinemia

PURPOSE: Hospital readmissions have recently increased due to early hospital discharge and increased trends in breast-feeding. Neonatal hyperbilirubinemia can lead to fatal permanent neurological sequelae without appropriate management. Early detection and intervention are critical. We evaluated the clinical features, risk factors, and brain MRI findings of Korean newborns with idiopathic nonhemolytic hyperbilirubinemia to determine the optimal management policy. METHODS: A retrospective review of the medical records of 79 newborns with idiopathic nonhemolytic hyperbilirubinemia was performed at the NICU of the Kyungpook National University Hospital from January 2006 to September 2009. All patients were 35 or more weeks of gestation, and their peak level of serum total bilirubin was more than 20 mg/dL. RESULTS: The mean gestational age was 38(+3)+/-1(+4) weeks, and the mean age on admission was 8.8+/-4.0 days. The mean body weight (3,105+/-479 g) was decreased by 2.8+/-6.4 percent compared to the mean birth weight (3,174+/-406 g). There were no statistically significant differences for the peak serum bilirubin level or the duration and effects of phototherapy between the patients with and without risk factors, which included: breastfeeding, cephalohematoma, subdural hemorrhage, and/or ABO incompatibility. Patients were grouped according to change of body weight. Group I consisted of patients that gained weight compared to birth weight, and group II of patients that lost weight compared to birth weight. There were significant differences in the peak serum total bilirubin level between the two groups. Thirty nine patients had brain MRI evaluation; 21 patients had bilateral symmetric signal intensity increases in the globus pallidus compared to adjacent corticospinal tract and putamen on T1-weighted images. CONCLUSION: Bilirubin encephalopathy is preventable with early screening and proper management. Parents require instruction on feeding practices and follow-up to prevent complications from idiopathic nonhemolytic hyperbilirubinemia.

The Clinical Characteristics According to the Risk Factors of Idiopathic Nonhemolytic Hyperbilirubinemia

PURPOSE: Hospital readmissions have recently increased due to early hospital discharge and increased trends in breast-feeding. Neonatal hyperbilirubinemia can lead to fatal permanent neurological sequelae without appropriate management. Early detection and intervention are critical. We evaluated the clinical features, risk factors, and brain MRI findings of Korean newborns with idiopathic nonhemolytic hyperbilirubinemia to determine the optimal management policy. METHODS: A retrospective review of the medical records of 79 newborns with idiopathic nonhemolytic hyperbilirubinemia was performed at the NICU of the Kyungpook National University Hospital from January 2006 to September 2009. All patients were 35 or more weeks of gestation, and their peak level of serum total bilirubin was more than 20 mg/dL. RESULTS: The mean gestational age was 38(+3)+/-1(+4) weeks, and the mean age on admission was 8.8+/-4.0 days. The mean body weight (3,105+/-479 g) was decreased by 2.8+/-6.4 percent compared to the mean birth weight (3,174+/-406 g). There were no statistically significant differences for the peak serum bilirubin level or the duration and effects of phototherapy between the patients with and without risk factors, which included: breastfeeding, cephalohematoma, subdural hemorrhage, and/or ABO incompatibility. Patients were grouped according to change of body weight. Group I consisted of patients that gained weight compared to birth weight, and group II of patients that lost weight compared to birth weight. There were significant differences in the peak serum total bilirubin level between the two groups. Thirty nine patients had brain MRI evaluation; 21 patients had bilateral symmetric signal intensity increases in the globus pallidus compared to adjacent corticospinal tract and putamen on T1-weighted images. CONCLUSION: Bilirubin encephalopathy is preventable with early screening and proper management. Parents require instruction on feeding practices and follow-up to prevent complications from idiopathic nonhemolytic hyperbilirubinemia.