Plasma and urine folate fractions were evaluated after ingestion of radioactive N5-methyl-tetrahydrofolic acid by a normal control (subject I), a patient on maintenance haemodialysis for chronic glomerulonephritis (subject 2), and an anephric patient on haemodialysis (subject 3). In subjects 1 and 2 maximal plasma radiofolate peaks appeared within 1 h of isotope ingestion. In subject 3 the radiofolate peak was delayed for 6 h although the total biofolate fraction reached a maximum at 0.5 h (comparable with findings in subject 2). Sephadex DEAE A50 chromatography showed the radiofolate fraction in subject I to be compatible with N5-methyl-tetrahydrofolic acid (peak I). In subject 2 additional radiofolate peaks 2 and 3 were found. The nature of peak 2 is unknown but peak 3 may represent 10-formyl-tetrahydrofolate. Peak I was minimally present in subject 3. This limited study suggest a defect of methyl-tetrahydrofolate metabolism in the anephric state unassociated with defective renal excretion per se. In normal urine, peak 2 predominated while urine of subject 2 had a predominant peak 3 and lesser peaks I and 2. Compared with the control, uraemic subjects 2 and 3 showed greatly decreased dialysis-resistant (bound plasma radiofolate fractions; all urinary radiofolates were fully dialysable. The unexplained radiofolate 'binder' detected with haemoglobin-coated charcoal adsorption in urine (subject 2) and occasionally in plasma, probably represents an artefact. Plasma from 27 uraemic subjects showed no abnormal in vitro radiofolate binding capacity.

Pulmonary epithelial cells may be responsible for regulating airway smooth muscle function, in part by release of fatty acid-derived mediators. Incubation of isolated guinea pig tracheal epithelial cells with radiolabeled arachidonic acid (AA) leads to the production of 5- and 15-hydroxyeicosatetraenoic acid (5- and 15-HETE) and smaller amounts of leukotriene (LT) B4 and C4 and 12-hydroxyheptadecatrienoic acid (HHT). Epithelial cells also are able to release linoleic acid (LA) metabolites. Incubation with radiolabeled linoleic acid leads to the formation of 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE). The biological significance of these mediators produced by epithelial cells is discussed.

After simultaneous ingestion of equivalent amounts of [3H]folic acid (3H‐PteGlu) and [14C]N5‐methyl‐tetrahydrofolic acid (14C‐CH3‐H4PteGlu) we were able to demonstrate progressive macromolecular binding of radiofolate in plasma, which appeared to be near maximal at 6 h. Bound radiofolate was predominantly of 14C‐CH3H4PteGlu origin, and only at 24 h could 3H incorporation be demonstrated. The binder eluted with albumin from Sephadex DEAE‐A50 columns. In urine a smaller bound radiofolate fraction, with approximately equal amounts of 3H and 14C, appeared after 5.5 h. Plasma chromatography showed radio‐PteGlu (peak 1) to be rapidly converted to CH3‐H4PteGlu (peak 2), with subsequent appearance of two further radiofolate peaks (peaks 3 and 4) the nature of which is as yet unclear. Urine showed similarly placed fractions but their magnitude differed, and urinary peak 3 in particular was much more prominent than its plasma counterpart.

It is useful to differentiate between saturated folate binders in serum (carrying endogenous folate) and unsaturated binders (investigated in the present study). These two groups of binders need not necessarily be chemically identical and the unsaturated binder may even be an in vitro artifact, especially when measured with non-physiological folates. Macromolecular binding of radio-active N-5-methyl tetrahydrofolic acid (CH3H4PteGlu) and/or folic acid (PteGlu) by human serum and urine was assessed by means of exhaustive saline dialysis, haemoglobin-coated charcoal adsorption, column chromatography with DEAE-Sephadex A-50, and sucrose gradient analysis. Binding was found to be minimal or absent. Charcoal adsorption showed a mean serum binding capacity of 0 mug/1. for PteGlu and 0.58 mug/1. for CH3H4PteGlu. In pregnancy the mean serum values were 0.23 mug/1. for PteGlu, 0.66 mjg/1. for CH3H4PteGlu, and with folate deficiency 0.30 mug/1. for PteGlu, 0.49 mug/1. for CH3H4PteGlu. Mean urinary folate binding was minimal (less than 0.5 mug/1.), and red cell haemolysate similarly revealed very low binding on exhaustive dialysis. Column chromatography showed that tracer doses of [14C]PteGlu added to serum migrated distally to the protein zone; [14C]CH3H4PteGlu similarly showed no evidence of protein binding. On a sucrose gradient [14C]PteGlu also separated clear of the protein zone.

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