The copolymerization of epsilon-caprolactone (epsilon-CL) and d,l-lactide catalyzed by Candida antarctica lipase B was studied. Copolymerizations with different epsilon-CL-to-lactide ratios were carried out, and the product was monitored and characterized by MALDI-TOF MS, GPC, and (1)H NMR. The polymerization of epsilon-CL, which is normally promoted by C. antarctica lipase B, is initially slowed by the presence of lactide. During this stage, lactide is consumed more rapidly than epsilon-CL, and the incorporation occurs dimer-wise with regard to the lactic acid (LA) units. As the reaction proceeds, the relative amount of CL units in the copolymer increases. The nonrandom copolymer structure disappears with time, probably due to a lipase-catalyzed transesterification reaction. In the copolymerizations with a low content of lactide, macrocycles of poly(epsilon-caprolactone) and copolymers having up to two LA units in the ring were detected.

Objectives Children with autism spectrum disorder (ASD) have been found to have a high prevalence of folate receptor autoantibodies (FRAA), which may impair the normal transport of folate from blood into the cerebrospinal fluid (CSF). Leucovorin calcium (LC) is believed to bypass the folate transport system and restore function. We sought to examine changes in behavior and urinary metabolites in children and young adults with ASD being treated with LC. Methods Students attending a K-12 school for ASD were recruited for an open-label, 12-week study of high-dose LC (2 mg/kg/ day, max dose 50 mg/day). The primary outcome measures were the mean changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). We also examined changes in Pediatric Quality of Life (PedsQL) and urinary metabolites. Changes were assessed with paired sample t-tests. Results Twelve students aged 13 to 19 (2 girls, 10 boys) completed the study. The parent-reported SRS showed a non-significant decrease (improvement) of 7.8 points (95% CI − 1.6 to 17.3, p = 0.095), and the ABC showed a non-significant decrease of 2.4 points (95% CI − 6.4 to 11.3, p = 0.56). The teacher-reported ABC and the parent-reported PedsQL showed very little change. Urinary metabolites with the greatest changes were involved in folate, phosphatidylcholine, and tocopherol metabolism. Conclusions In an open-label study of school-aged children with ASD, LC treatment did not lead to significant improvements. The parent-reported SRS showed a non-significant improvement of 7.8 points, which is clinically important and worthy of future study with larger samples. The potential benefits of LC may be limited to children with a specific physiological abnormality (e.g., FRAA status) and may require a targeted treatment approach. Urinary metabolites may be a useful tool to identify children who are likely to respond to treatment.

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