Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells

We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of　CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction

Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

Peer reviewe

Hostmedicin förstärkte effekten av warfarin: Cocillana-Etyfin höjde PK(INR)-värdet

De i artikeln beskrivna fallen visar på en potentiell interaktion mellan Cocillana-Etyfin och warfarin, med risk för allvarliga blödningar som följd. Stor vaksamhet och rapportering av misstänkta biverkningar och interaktioner är av stor vikt för att säkerställa en säker och rationell läkemedelsanvändning.</p

Beryllium mineralization in the Ilímaussaq intrusion, South Greenland

In the peralkaline Ilimaussaq intrusion in South Greenland minor quantities of beryllium minerals are widespread in hydrothermal veins. Concentrations of veins rich in beryllium minerals are known from the Taseq slope and the Kvanefjeld area in the northern part of the intrusion. Up to now 10 beryllium minerals have been found, the most important being chkalovite. The hydrothermal veins range in width from about 1 mm to 2 m but are mostly a few cm thick. The most important minerals in the veins are analcime, sodalite, ussingite, natrolite, aegirine, arfvedsonite, epistolite and chkalovite. A field beryllometer based on the photoneutron method of determining beryllium is described. With a 100 mCi Sb124 activation source the instrument has a limit of detection ofless than 10 ppm BeO. The effective measuring area is ca. 40 cm2. Beryllium has a log-normal distribution in the rocks of the area.</jats:p