Meal-related oscillations in the serum serotonin levels in healthy young men.

CONTEXT: Serotonin acts as a neurotransmitter in the central and enteric nervous systems, modulating psychological, metabolic and gastrointestinal functions. Serotonin is also found in the serum or plasma, indicating its potential role as a hormone. OBJECTIVE: We aimed to assess the 24-hour diurnal profile of serum serotonin in relation to meal ingestion in healthy adult men. METHODS: Ten healthy (5 lean and 5 obese) male subjects were enrolled in this study. Blood samples were drawn every 30-60 minutes throughout a 24-hour period to determine the serotonin levels. Three meals were provided on a fixed schedule. To confirm the effect of meal intake on serum serotonin levels, 4 subjects underwent fasting until 1500 h and were then provided a meal without notice. RESULTS: Serum serotonin levels had distinct diurnal variations, with the highest levels early in the morning and the lowest levels in the midafternoon and during sleep. Notably, these diurnal oscillations were markedly reduced in obese subjects. Fluctuations in serum serotonin levels were associated with meal intake, and the levels peaked 30 minutes before meals and exhibited a trough during the postprandial period. Fasting blunted the meal-related oscillations in serum serotonin levels. Moreover, unexpected meal intake did not lead to a premeal increase in serum serotonin levels. CONCLUSIONS: Serum serotonin levels displayed meal-related diurnal oscillations, which were disrupted by fasting and obesity. These findings suggest the possibility that circulating serotonin modulates metabolic function in humans.

Independent associations of circulating 25-hydroxyvitamin D and parathyroid hormone concentrations with blood pressure among Koreans: The Korea National Health and Nutrition Examination Survey (KNHANES), 2009-2010.

Although lower vitamin D and higher parathyroid hormone (PTH) concentrations have been associated with hypertension, their independent contribution to blood pressure (BP) is unclear. The independent associations of serum 25-hydroxyvitamin D (25[OH]D) and PTH levels with BP were therefore investigated. This is a population-based cross-sectional study from the Korea National Health and Nutrition Examination Surveys, which includes a total of 4,513 participants (2,019 men and 2,494 women) aged ≥ 50 years. 25(OH)D and PTH were measured by radioimmunoassays, and BP was determined with a sphygmomanometer. Hypertensive subjects had significantly lower 25(OH)D (p = 0.023) and significantly higher PTH (p < 0.001) concentrations than normotensives. In subjects not taking antihypertensive medications, 25(OH)D showed reverse correlations with systolic and diastolic BP, both in men (p = 0.038-0.061 and p = 0.011-0.038, respectively) and in women (p = 0.006-0.018 and p = 0.001-0.011, respectively), while serum PTH concentrations showed positive correlations with systolic and diastolic BP in men (p = 0.001-0.014 and p < 0.001, respectively) and women (p < 0.001-0.008 and p = 0.001-0.040, respectively). When 25(OH)D and PTH were included in the same model, both remained independently associated with BP in men and women. In conclusion, both lower 25(OH)D and higher PTH may be independent factors for the development of hypertension.

[The prognostic factors of pancreatic cancer can be different according to clinical stages].

BACKGROUND/AIMS: The prognosis of patients with pancreatic cancer remains very poor. Although many studies have evaluated the prognostic factors of pancreatic cancer, their results are inconclusive because of different inclusion criteria, tumor stages, and treatment modalities. This large scale retrospective analysis was performed to assess whether active treatment of pancreatic cancer, even in its advanced stage, could improve patients' survival. In addition, we sought to identify factors associated with favorable prognosis of pancreatic cancer. METHODS: Between 1994 and 2004, a total of 971 patients with pancreatic cancer were treated at Asan Medical Center. The patients were classified into three groups according to clinical stages: resectable (RE, n=226), locally advanced (LA, n=409), and far advanced (FA, n=336). Treatment response and prognostic factors for survival were analyzed in each group. RESULTS: Compared to supportive care, active treatment significantly increased the median survival time in all groups (RE: 18.0 vs. 9.0 months; LA: 10.0 vs. 7.0 months; FA: 5.0 vs. 3.0 months). Multivariate analysis showed that prognostic factors for survival differed according to clinical stages. In the RE group, unfavorable prognostic factors were high CA 19-9, poor histologic differentiation, large tumor size, and regional lymph node involvement. In the FA group, however, poor outcomes were associated with old age, poor performance status, and hypoalbuminemia. CONCLUSIONS: More active treatment of pancreatic cancer, even in advanced stage, can make a significant difference in terms of patient's survival. The prognosis of resectable pancreatic cancer is dependent on tumor-related factors, while the prognosis of patients with far advanced pancreatic cancer is dependent on patient-related factors.

Distinct Ultradian Rhythms in Plasma Clusterin Concentrations in Lean and Obese Korean Subjects.

BACKGROUND: Blood levels of many hormones show rhythmic fluctuations with variable duration of cycles. Clusterin/apolipoprotein J is a glycoprotein which is highly expressed in the plasma and has modulatory roles in immune and inflammatory reactions, neurobiology, lipid metabolism, and leptin signaling. In this study, we examined the diurnal fluctuations of plasma clusterin concentrations in lean and obese young men. METHODS: For the study, 14 subjects (five lean and five obese men; two lean and two obese women) were admitted to the research ward and blood samples were drawn every 30 minutes during light-on period (6:00 AM to 10:00 PM) and every hour during light-off period. RESULTS: Notably, plasma clusterin concentrations displayed a unique ultradian rhythm with five cycles a day in both men and women. During the light-on period, circulating clusterin levels showed fluctuating curves with 4 hours regular intervals with sharp peaks and troughs. In contrast, single oscillation curve during light-off exhibited a smoothened/lower peak and longer (8-hour) duration. In obese men, these cycles were phase-advanced by approximately 1 hour, and had reduced amplitude of fluctuating curves and blunted diurnal pattern. Cyclic fluctuations of plasma clusterin were preserved under fasting and unexpected meal condition, suggesting that rhythmic oscillations in plasma clusterin levels are not generated by meal-related cues. CONCLUSION: These findings firstly demonstrate a novel pattern of plasma clusterin fluctuations with extremely regular cycles.

Prevalence of angiographically defined obstructive coronary artery disease in asymptomatic patients with type 2 diabetes according to the coronary calcium score.

OBJECTIVE: The aim of this study was to determine whether the absence of coronary artery calcium (CAC) can safely exclude obstructive coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes. METHODS: We enrolled 478 consecutive asymptomatic patients with type 2 diabetes who visited the diabetes clinic of the Asan Medical Center between October 1, 2009 and December 31, 2010. All patients underwent 64-slice dual-source computed tomography (DSCT) for CAC scoring as well as computed tomography angiography (CTA). Patients with at least one significant coronary stenosis with >50% luminal narrowing were classified as having obstructive CAD. The findings were confirmed using conventional coronary angiography (CAG). RESULTS: Among the 478 patients, 157 (33%) had a CAC score of 0 (CAC=0). Of these, 17 (11%) had obstructive CAD confirmed on CAG. The presence of CAC had a negative predictive value for obstructive CAD on CAG of 89% and a sensitivity of 88%, a specificity of 42% and a positive predictive value of 38%. A multivariate logistic regression analysis showed that current smoking habits were significantly associated with the presence of obstructive CAD in patients with CAC=0 after adjusting for traditional cardiovascular risk factors (odds ratio 4.87, 95% confidence interval 1.65-14.42, p=0.004). CONCLUSION: Our findings suggest that CAC=0 on 64-slice DSCT cannot safely exclude obstructive CAD on CAG in asymptomatic patients with type 2 diabetes, particularly in current smokers. CTA should be combined with CAC scoring in screening for CAD in asymptomatic patients with type 2 diabetes.

Effects of alpha-lipoic Acid on body weight in obese subjects.

PURPOSE: alpha-lipoic acid is an essential cofactor for mitochondrial respiratory enzymes that improves mitochondrial function. We previously reported that alpha-lipoic acid markedly reduced body weight gain in rodents. The purpose of this study was to determine whether alpha-lipoic acid reduces body weight in obese human subjects. METHODS: in this randomized, double-blind, placebo-controlled, 20-week trial, 360 obese individuals (body mass index [BMI] ≥ 30 kg/m(2) or BMI 27-30 kg/m(2) plus hypertension, diabetes mellitus, or hypercholesterolemia) were randomized to alpha-lipoic acid 1200 or 1800 mg/d or placebo. The primary end point was body weight change from baseline to end point. RESULTS: the 1800 mg alpha-lipoic acid group lost significantly more weight than the placebo group (2.1%; 95% confidence interval, 1.4-2.8; P<.05). Urticaria and itching sensation were the most common adverse events in the alpha-lipoic acid groups, but these were generally mild and transient. CONCLUSION: alpha-lipoic acid 1800 mg/d led to a modest weight loss in obese subjects. Alpha-lipoic acid may be considered as adjunctive therapy for obesity.

Circadian rhythm of serum vaspin in healthy male volunteers: relation to meals.

CONTEXT: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with insulin-sensitizing effects. However, the physiological role for vaspin in human metabolic regulation remains to be established. OBJECTIVE: We studied the 24-h profiles of circulating vaspin concentrations in relation to meal ingestion in normal adults. DESIGN: Blood samples were drawn 39 times throughout a 24-h period from 10 healthy male subjects provided with meals on a fixed schedule. On a separate day, four subjects were fasted and then provided with an unexpected meal to clarify the effect of meal consumption on serum vaspin levels. Serum vaspin concentrations were determined by ELISA. RESULTS: Serum vaspin levels were highest in the early morning before breakfast and fell to trough levels within 2 h after breakfast. Serum vaspin levels also showed a preprandial rise and postprandial fall at lunch and dinner, although at lesser degrees than at breakfast. Intermeal vaspin concentrations reached a nadir in the mid-afternoon and showed a nocturnal rise, with peak nighttime vaspin levels being approximately 250% of nadir levels. Unscheduled food ingestion after a prolonged fast significantly reduced serum vaspin levels, suggesting that energy intake itself has a suppressive effect on serum vaspin levels. The diurnal pattern of serum vaspin concentrations was exactly reciprocal to that of insulin and of glucose. CONCLUSION: Serum vaspin levels have a meal-related diurnal variation, suggesting a role for vaspin in metabolic regulation. However, the reciprocal relationship between serum vaspin and insulin may negate the importance of vaspin as an physiological insulin sensitizer.

A case of anaphylaxis to chlorhexidine during digital rectal examination.

Chlorhexidine is widely used as an antiseptic and disinfectant in medical and nonmedical environments. Although the sensitization rate seems to be low, its ubiquitous use raises the possibility of sensitization in many patients and medical care workers. We describe a patient with anaphylaxis during digital rectal examination with chlorhexidine jelly. Urticaria, angioedema, dyspnea, and hypotension developed within a few minutes of the rectal examination. The patient fully recovered after treatment with epinephrine and corticosteroids. Skin tests for chlorhexidine were undertaken 5 weeks later, showing positive prick and intradermal skin tests. Within 30 min of the skin test, the patient complained of febrile sensation, chest tightness, angioedema, and urticaria on the face and trunk. An enzyme allergosorbent test for latex was negative. We present this case to alert clinicians about hypersensitivity to chlorhexidine that could potentially be life-threatening. We suggest that chlorhexidine should be recognized as a causative agent of anaphylaxis during procedural interventions.