alpha isoforms of soluble and membrane-linked folate-binding protein in human blood

International audienceThe high affinity folate binding protein/ folate receptor (FBP/FR) is expressed in three isoforms. FR alpha and beta are attached to cell membranes by hydrophobic glycosylphosphatidyl inositol (GPI) anchors, while FBP gamma is a secretory protein. Mature neutrophil granulocytes contain a non-functional FR beta on the surface , and in addition nanomolar concentrations of a secretory functional FBP (29 kDa) can be present in the secondary granules. A statistically significant correlation between the concentrations of functional FBP, probably a gamma isoform, in granulocytes and serum supported the hypothesis that serum FBP (29 kDa) mainly originates from neutrophils. The presence of FBP/FR alpha isoforms were for the first time established in human blood using antibodies specifically directed against human milk FBP alpha. The alpha isoforms identified on erythrocyte membranes, and in granulocytes and serum only constituted an almost undetectable fraction of the functional FBP. The alpha FBP in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of alpha FBP (> 120 kDa) which could represent receptor fragments from decomposed erythrocytes and granulocytes. The soluble FBPs may exert bacteriostatic effects and protect folates in plasma from biological degradation, while FRs on the surface of blood cells could be involved in intracellular folate uptake or serve as signal proteins. The latter receptors have also been used for therapeutic targeting in malignancy

Associations between treatment with melatonin and suicidal behavior: a nationwide cohort study

Study Objectives: Melatonin is often prescribed to patients with sleep disorders who are known to have elevated suicide risks. Yet, melatonin’s association to suicidal behaviour remains to be examined. We investigated whether individuals prescribed melatonin had higher rates of suicide and suicide attempts when compared to individuals who were not prescribed this drug, including both those with and without known mental disorders. Methods: A cohort design was applied to longitudinal, register data on all persons aged 10+ years in Denmark during 2007-2016. Based on data from the National Prescription Register, periods of being in treatment with melatonin were defined using information on number of tablets and daily defined dose. We calculated IRR for suicide and suicide attempts, as identified in register records, comparing those in treatment with melatonin to those not in treatment. Results: Among 5,798,923 individuals, 10,577 (0.2%) were treated with melatonin (mean treatment length 50 days) during the study period. Of those, 22 died by suicide and 134 had at least one suicide attempt. People in treatment with melatonin had a 4-fold higher rate of suicide (IRR: 4.8; 95% CI, 3.0-7.5) and a 5-fold higher rate of suicide attempt (IRR: 5.9; 95% CI,4.4-8.0) than those not in treatment and when adjusting for sex and age-group. Conclusions: Treatment with melatonin was associated with suicide and suicide attempt. While there are several possible explanations, attention to suicide risk is particularly warranted for people with mental comorbidity who are in treatment with melatonin.</p