Biomarkers for febrile urinary tract infection in children.

BACKGROUND: The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. METHODS: This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. RESULTS: We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. CONCLUSIONS: NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

Influence of a high-temperature programme on serum, urinary and sweat levels of selenium and zinc.

INTRODUCTION: The effect of hyperthermia on the antioxidant system in the human organism is well known. AIM: The objective of this study was to observe the effects of heat on the concentration of Se and Zn, elements related to antioxidant systems. METHODS: Twenty-nine subjects voluntarily participated in this study. They were divided into a control group (CG; n = 14) and an experimental group (EG; n = 15). All of them underwent two incremental tests until exhaustion in normothermia (22 °C, 20-40%RH) and hyperthermia (42 °C, 20-40%RH). EG experienced nine sessions of repeated heat exposure at high temperatures (100 °C, 20%RH) for three weeks (HEHT). After the intervention, the initial measurements were repeated. Urine and blood samples were collected before and after each test. Additionally, sweat samples were collected after tests in hyperthermia. RESULTS: There were no significant changes in serum. An increase in the elimination of Zn and Se in EG was observed in urine after HEHT (p < .05). The elimination of Zn by sweating decreased after HEHT in EG (p < .05). CONCLUSIONS: Exposure to heat at high temperatures increases the urinary excretion of Se and Zn.

Serum and urine metabolomics based on UPLC-Q-TOF/MS reveals the antipyretic mechanism of Reduning injection in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDN), a patented traditional Chinese medicine, has the obvious antipyretic effect and has been widely used in China. Although some previous studies proved its antipyretic effect by animal efficacy experiment or clinical observation, its holistic mechanism in vivo was still unclear. AIM OF THE STUDY: To comprehensively elucidate the antipyretic mechanism of RDN, the investigation of fever-related potential biomarkers and metabolic pathways in the rat fever model is described in this paper. MATERIALS AND METHODS: Rat fever model was established by dry yeast. A large number of endogenous metabolites in serum and urine were detected by UPLC-Q-TOF/MS, and fever-related potential biomarkers were screened and identified by multivariate analysis and metabolite databases. The reliability and biological significance of the largely disturbed biomarkers was verified by the metabolic network and the correlation with pharmacodynamic indicators, which contained IL-1ß, IL-6, TNF-α, PGE2 and cAMP. RESULTS: The established UPLC-Q-TOF/MS analytical method afforded satisfactory results in terms of precision, repeatability and stability, which met the requirements of biological sample determination. A total of 32 potential biomarkers associated with fever were screened and identified, among which 22 species could be adjusted by RDN. The metabolism pathway analysis revealed that valine, leucine and isoleucine biosynthesis, and sphingolipid metabolism were greatly disturbed. Their biomarkers involved L-leucine, L-valine, sphinganine and phytosphingosine, all of which showed a callback trend after RDN was given. These 4 biomarkers had a certain correlation with some known fever-related small molecules and pharmacodynamic indicators, which indicated that the selected fever-related biomarkers had certain reliability and biological significance. CONCLUSIONS: RDN has a good regulation of the metabolic disorder of endogenous components in dry yeast-induced fever rats. Its antipyretic mechanism is mainly related to the regulation of amino acid, lipid and energy metabolism. The study is useful to better understand and analyze the pharmacodynamic mechanism of complex systems, such as traditional Chinese medicine.

Effect of huanglianjiedu tang on fever in rats induced by 2, 4-dinitrophenol.

OBJECTIVE: To study metabolic characteristics of fever in rats induced by 2, 4-dinitrophenol (DNP) and the effect of Huanglianjiedu Tang (HLJDT) on the fever. METHODS: The urine samples were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) at the positive ion mode scanning, and experimental data were analyzed by the principal component analysis. RESULTS: Eight potential biomarkers indicating the occurrence and evolvement of fever were determined according to ions in urine samples. Five of them were found increased, while the other three decreased. After HLJDD intervention, the increased five were reduced significantly in high dose group, compared with model group, while the decreased three had no obvious change. Five of the eight biomakers were identified with formyl-5-hydroxykynurenamine, gentisic acid, aminoadipic acid, phenylacetic acid, L-phenylalanyl-L-hydroxyproline on the basis of MS/MS. These biomarkers are associated with the metabolism of 5-hydroxytryptamine, tyrosine, lysine, phenylalanine and collagen protein, respectively. CONCLUSION: HLJDT had significant effect on DNP-induced fever in rats. The effect was performed possibly by acting on 5-hydroxytryptamine in hypothalamus and some amino acid metabolism. These results suggested that HLJDT relieved fever by acting on multi-targets.

Metabolomic study of a rat fever model induced with 2,4-dinitrophenol and the therapeutic effects of a crude drug derived from Coptis chinensis.

This study describes the metabonomics of fevers in animal models and the therapeutic effects of Rhizoma coptidis extract (RCE) on them. The rat urinary samples were analyzed by UPLC/ ESI-Q-TOF/MS, combined with principal component analysis (PCA). Nine ions were chosen to characterize the similarities and differences in the responses to fever. The ion at m/z 206.0278 was unambiguously identified to be xanthurenic acid. This study demonstrated that the metabonomic approach can readily distinguish between febrile and healthy individuals. This data support the contention that the metabonomic approach represents a promising new technology for the development of rapid-throughput in vivo fever screening. Furthermore, this approach can detect the interfering effects of RCE. This investigation has led the authors to believe that metabonomics is a valid approach for explaining the therapeutic effects of traditional Chinese medicine on fevers.