<b><i>Background: </i></b>Obesity is a growing problem throughout Europe, where the rate has more than doubled over the past 20 years. Reduced circulating serotonin may contribute to the development of obesity. This study aimed to explore associations between whole blood (WB) serotonin concentrations and anthropometric measures. <b><i>Methods: </i></b>Healthy adult volunteers (N = 68) gave whole blood samples for measurement of WB serotonin, and underwent BMI waist circumference (WC) and waist-to-hip ratio (WHR) assessment as well as DEXA (dual energy X-ray absorptiometry) scans for anthropometric parameters. Student’s t-tests determined differences in WB serotonin and anthropometric measures between sexes. Partial Pearson’s correlations were carried out on anthropometric measures and WB serotonin. <b><i>Results: </i></b>For the whole sample, WB serotonin was significantly negatively correlated with BMI, WC, WHR as well as android, gynoid and total % body fat. Analysis by sex showed significant negative correlations between WB serotonin and android, gynoid as well as total fat in males, but not in females. <b><i>Conclusion: </i></b>This dichotomy between the sexes implies that there may be sex differences in the way that serotonin interplays with the development of obesity and body fat distribution.

SUMMARY. Carbamylated haemoglobin arises from the non-enzymic modification of haemoglobin monomers by isocyanate derived from the spontaneous dissociation of urea. We measured carbamylated haemoglobin by high performance liquid chromatography in healthy subjects, non-uraemic hospital patients, diabetics, and different groups of uraemic patients. Carbamylated haemoglobin levels were found to be raised in uraemic subjects, but were independent of age, sex, glycaemic state and haemodialysis procedure. There was no significant difference in carbamylated haemoglobin levels between two groups of patients having different modes of dialysis treatment, probably indicating a similar degree of uraemic exposure in these patients. Additional key phrases: glycated haemoglobin; protein carbamylation; chronic renal failureCarbamylation of the haemoglobin molecule by isocyanic acid, the reactive form of cyanate in aqueous solution which derives from the spontaneous dissociation of urea, can take place at either the amino groups of the amino-terminal valine residues or the s-amino groups of lysine residues of both ex and (3chains. However, at physiological pH, the amino-terminal groups are carbamylated 50 to 100 times faster than the s-amino groups.' Cyanate has been used as an anti-sickling agent," but was abandoned due to the appearance of peripheral neuropathies.! subcapsular cataracts and weight loss in subjects maintained on long-term oral cyanate therapy.! These toxic manifestations of cyanate therapy are not dissimilar to some of the symptomatology seen in uraemia, thus raising the possibility of protein carbamylation having a role in the mechanism of uraemic toxicity.Fliickiger and co-workers, using a gas-liquid chromatography method, first demonstrated elevated levels of carbamylated haemoglobin in uraemic patients and showed that the levels correlated well with the time-averaged urea concentrations in haemodialysis patients." They

Urea kinetic modelling (UKM) has increasingly been used for assessing adequacy of dialysis and protein nutritional status of dialysis patients. Using a precise HPLC method we developed, we measured carbamylated haemoglobin (CarHb) values in 20 stable twice-weekly dialysed patients and attempted to correlate their CarHb values with their UKM-derived indices. Based on these indices, 11 patients were found to have been adequately dialysed with sufficient protein intake, three patients were adequately dialysed but malnourished and six patients were under-dialysed. Estimated dietary protein intake correlated poorly with calculated daily protein catabolic rate in our patients. CarHb values were found to correlate strongly with the time-averaged urea concentrations, suggesting that CarHb might be a time-integrated urea-derived index. Those adequately dialysed patients have a mean (SD) CarHb value of 142 (29) micrograms CV/gHb against the underdialysed patients, 197 (30) micrograms CV/gHb (t-test, P = 0.002). We suggest that a CarHb value less than 175 micrograms CV/gHb may represent satisfactory uraemic exposure, whereas CarHb value greater than 175 micrograms CV/gHb is undesirable.

We have developed an HPLC method for measuring carbamylated hemoglobin (CarHb), based on the quantification of valine hydantoin formed from the released NH2-terminal carbamyl valine residue after acid hydrolysis of hemoglobin. In uremia, CarHb is produced by nonenzymatic post-translational modification of the terminal amino group of hemoglobin monomers by isocyanic acid, derived from the spontaneous dissociation of urea. We measured CarHb in 25 nonuremic control subjects, 24 nonuremic diabetic subjects, and 30 patients with stable chronic renal failure. There was no significant difference between the controls and diabetic patients, their mean (SD) CarHb values being 41 (11.5) and 38 (10.8) micrograms of carbamyl valine per gram of hemoglobin (microgram CV/gHb), respectively. Mean (SD) CarHb values in the uremic patients were much greater, 164 (87.7) microgram CV/gHb. There was significant correlation between the concentrations of CarHb and plasma urea in the uremic subjects. Thus CarHb provides a urea-derived index of chronic uremia.

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