Greatly Increased Numbers of Histamine Cells in Human Narcolepsy With Cataplexy.

Greatly increased numbers of histamine cells in human narcolepsy with cataplexy.

Ann Neurol. 2013 Jul 2;
John J, Thannickal TC, McGregor R, Ramanathan L, Ohtsu H, Nishino S, Sakai N, Yamanaka A, Stone C, Cornford M, Siegel JM

To determine whether histamine cells are altered in human narcolepsy with cataplexy, and in animal models of this disease.Immunohistochemistry for histidine decarboxylase (HDC) and quantitative microscopy were used to detect histamine cells in human narcoleptics, Hcrt receptor-2 mutant dogs and three mouse narcolepsy models: hypocretin (Hcrt, orexin) knockouts (KOs), ataxin-3-orexin and doxycycline-controlled-diphtheria-toxin-A-orexin (DTA).We find an average 64% increase in the number of histamine neurons in human narcolepsy with cataplexy, with no overlap between narcoleptics and controls. However, we do not see altered numbers of HDC cells in any of the animal models of narcolepsy we examined.Changes in histamine cell numbers are not required for the major symptoms of narcolepsy, since all animal models have these symptoms. The histamine cell changes we saw in humans did not occur in the four animal models of hypocretin dysfunction we examined. Therefore the loss of Hcrt receptor-2, of the Hcrt peptide, or of Hcrt cells is not sufficient to produce these changes. We speculate that the increased histamine cell numbers we see in human narcolepsy may instead be related to the process causing the human disorder. Although research has focused on possible antigens within the Hcrt cells that might trigger their autoimmune destruction, the present findings suggest that the triggering events of human narcolepsy may involve a proliferation of histamine containing cells. We discuss this and other explanations of the difference between human narcoleptics and animal models of narcolepsy, including therapeutic drug use and species differences. ANN NEUROL 2013. © 2013 American Neurological Association. HubMed – drug

Comparison of the quantitative performance of a Q-Exactive high-resolution mass spectrometer with that of a triple quadrupole tandem mass spectrometer for the analysis of illicit drugs in wastewater.

Rapid Commun Mass Spectrom. 2013 Aug 15; 27(15): 1751-1762
Fedorova G, Randak T, Lindberg RH, Grabic R

Analysis of drugs in wastewater is gaining more interest, as new approaches to estimate drug consumption from the amount of drug residues in wastewater have been proposed. The aim of this study was to compare the quantitative performance of high-resolution mass spectrometry with that of triple quadrupole mass spectrometry.A Q-Exactive mass spectrometer was operated in full scan (HRFS) (70 000 FWHM) and product scan (HRPS) (17 500 FWHM) modes. The first and third quadrupoles of the QqQ MS/MS instrument were operated at 0.7 FWHM. A mass-extracted window of 5?ppm around the theoretical m/z of each analyte was used to construct chromatograms. An HESI-II ion source was used for the ionization of target compounds. In-line-SPE-LC configuration was used for the extraction and separation of target analytes.All three methods showed good linearity and repeatability. High-resolution detection of product ions exhibited better sensitivity and selectivity for some compounds. For most of the tested compounds, LOQs ranged from 0.46 to 20?ng?L(-1) . Good agreement between measured and nominal concentrations was observed for most of the compounds at different levels of fortification. Both MS/MS methods showed good selectivity, while HRFS gave some false positive results.The Q-Exactive mass spectrometer proved to be suitable for trace detection and quantification of most of the tested drugs in wastewater, with performance comparable to that of the commonly used MS/MS triple quadrupole, but with better selectivity. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – drug

Activation of aryl hydrocarbon receptor by Tranilast, an anti-allergy drug,promotes miR-302 expression and cell reprogramming.

J Biol Chem. 2013 Jul 2;
Hu W, Zhao J, Pei G

MiR-302 has been shown to regulate pluripotency-controlled genes and help somatic cell reprogramming. Thus promotion of endogenous miR-302 expression could be a desirable way to facilitate cell reprogramming. By using a luciferase reporter system of miR-302 promoter, we screened and found that an anti-allergy drug, tranilast can significantly promote miR-302 expression. Further experiments reveal that two aryl hydrocarbon receptor (AhR) binding motifs on miR-302 promoter are critical and activation of AhR is required for tranilast-induced miR-302 expression. Consistently, not only tranilast but other AhR agonists promote miR-302 expression. Furthermore, activation of AhR facilitates cell reprogramming in a miR-302 dependent way. These results elucidate miR-302 expression can be regulated by AhR and thus provide a strategy for promoting somatic cell reprogramming by AhR ligands. HubMed – drug