Urinary lipid profile of atopic dermatitis in murine model and human patients.

Atopic dermatitis (AD) is the most common inflammatory skin disease in children. The serum level of thymus and activation-regulated chemokine (TARC) is a useful AD index to reflect disease severity; however, it requires blood collection from young children. In comparison, urine samples are easier to collect in a pediatric clinical setting. Here, we analyzed the lipids excreted in urine to identify a diagnostic biomarker for AD. We generated a murine dermatitis model by repeated topical application of 2,4-dinitrofluorobenzene (DNFB) or tape-stripping the dorsal skin. Lipid metabolites excreted in the urine were comprehensively analyzed using liquid chromatography-tandem mass spectrometry. To corroborate our findings, we also analyzed urine samples from patients with AD. DNFB application induced AD-like skin lesions, including epidermal thickening, infiltration of eosinophils and T cells, and an increase in Th2 cytokine levels. Assessment of lipids excreted in urine showed a dominance of prostaglandins (PGs), namely, a PGF2α metabolite (13,14-dihydro-15-keto-tetranor-PGF1α ), a PGE2 metabolite (13,14-dihydro-15-keto-tetranor-PGE2 ), and a PGD2 metabolite (13,14-dihydro-15-keto PGJ2 ). mRNA and protein expression of PGF2α , PGE2 , and PGD2 synthase was upregulated in DNFB-treated skin. The tape-stripping model also caused dermatitis but without Th2 inflammation; urine PGF2α and PGD2 metabolite levels remained unaffected. Finally, we confirmed that the urinary levels of the aforementioned PG metabolites, as well as PGI2 metabolite, 6,15-diketo-13,14-dihydro-PGF1α and arachidonic acid metabolite, 17-hydroxyeicosatetraenoic acid (17-HETE) increased in patients with AD. Our data highlights the unique urinary lipid profile in patients with AD, which may provide insight into novel urinary biomarkers for AD diagnosis.

Ocular drift reflects volitional action preparation.

Human cognitive behavior is predictive rather than reflexive because of volitional action preparation. Recent studies have shown that the covert process of volitional action preparation can be decoded from overt fixational eye movements of fixational/microsaccades and pupil dilation. Ocular drift, the slowest fixational eye movements, is also under the active neural control, but its relationship with cognitive behavior is unknown. Here, we examined whether ocular drift also reflects volitional action preparation. We analyzed ocular drift while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade. We adopted the antisaccade paradigm in which subjects generate a targeting saccade toward the opposite direction of a peripheral visual stimulus. Our findings are the following five points. First, ocular drift was slower when subjects prepared for targeting saccade initiation than when such preparation was unnecessary. Second, ocular drift was slowed down with elapsed time from fixation initiation, which was associated with the facilitation of targeting saccade initiation. Third, ocular drift was further slowed on correct antisaccade trials than when subjects failed to suppress targeting saccades toward peripheral stimuli. Fourth, such correlation with antisaccade performance was observed immediately after fixation initiation in ocular drift, but it emerged more slowly in the other fixational eye movements. Fifth, subjects with unstable fixation because of faster ocular drift had poorer antisaccade performance. We suggest that fixation stability measured by ocular drift can be used to decode the covert process of volitional action preparation along with the other fixational eye movements.

The profile of lipid metabolites in urine of marmoset wasting syndrome.

Marmoset wasting syndrome (MWS) is clinically characterized by progressive weight loss. Although morbidity and mortality of MWS are relatively high in captive marmosets, its causes remain unknown. Lipid mediators are bioactive metabolites which are produced from polyunsaturated fatty acids, such as arachidonic acid (AA) and eicosapentaenoic acid. These lipid metabolites regulate a wide range of inflammatory responses and they are excreted into the urine. As urinary lipid profiles reflect systemic inflammatory conditions, we comprehensively measured the levels of 141 types of lipid metabolites in the urines obtained from healthy common marmoset (Callithrix jacchus) (N = 7) or marmosets with MWS (N = 7). We found that 41 types of metabolites were detected in all urine samples of both groups. Among them, AA-derived metabolites accounted for 63% (26/41 types) of all detected metabolites. Notably, the levels of AA-derived prostaglandin (PG) E2, PGF2α, thromboxane (TX) B2 and F2-isoprostanes significantly increased in the urine samples of marmosets with MWS. In this study, we found some urinary lipid metabolites which may be involved in the development of MWS. Although the cause of MWS remains unclear, our findings may provide some insight into understanding the mechanisms of development of MWS.