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. Holtze M, Mickiené A, Atlas A, Lindquist L, Schwieler L (Karolinska Institutet, Stockholm; Lithuanian University of Health Sciences, Kaunas, Lithuanian; Karolinska Institutet, Karolinska University Hospital, Huddinge; Karolinska Institutet, Karolinska University Hospital, Solna, Sweden). Elevated cerebrospinal fluid kynurenic acid levels in patients with tick-borne encephalitis. J Intern Med 2012; 272: 394-401. Background. Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan that is thought to regulate cognitive functions. Previous studies have shown that levels of KYNA increase during virus infection and that this metabolite interacts with the immune system. Objective. The aim of the study was to investigate whether patients with tick-borne encephalitis (TBE), a viral infectious disease associated with long-term cognitive impairment, have increased levels of KYNA in the cerebrospinal fluid (CSF). Methods. CSF KYNA was analysed using high-performance liquid chromatography in 108 patients with TBE and 52 age-matched controls. Patients were classified according to the severity of TBE: mild (47%), moderate (44%) or severe (9%). Results. Concentrations of CSF KYNA were considerably higher in patients with TBE (5.3 nmol L−1) than in control subjects (0.99 nmol L−1). KYNA concentration in the CSF varied greatly amongst individuals with TBE and increased ( P < 0.05) with the severity of disease. Conclusions. This is the first study to demonstrate increased levels of CSF KYNA in patients with TBE. The importance of brain KYNA in both immune modulation and neurotransmission raises the possibility that abnormal levels of the compound in TBE might play a part in the pathophysiology of the disease. A detailed knowledge of endogenous brain KYNA during the course of CNS infection might yield further insights into the neuroimmunological role of the compound and may also provide new pharmacological approaches for the treatment of cognitive symptoms. [ABSTRACT FROM AUTHOR]

Background & Aims: There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI., Methods: Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study., Results: In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury., Conclusions: M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)