We found that as a consequence of an acidic milieu and/or oxidative stress the copper-binding capacity of serum albumin strongly declined, leading to significant dissociation of copper ions into the ambient solution. At physiologically relevant pH-values Cu2+ ions in combination with physiologically available copper reductants (i.e., ascorbate, glutathione, Fe2+) significantly enhanced nitrite

reduction and subsequent non-enzymatic NO generation under hypoxic but also normoxic conditions. Our data demonstrate for the first time that upon ischemic conditions carrier protein-dissociated copper ions combined with appropriate reductants may serve as Cu1+-driven catalytic sites for nitrite reduction, leading to the formation of biologically relevant NO formation. Thus, in addition to the action of heme proteins, copper-catalyzed non-enzymatic NO formation from nitrite might represent a further Eltanexor chemical structure physiologically relevant vasodilating and NO-dependent protective principle to ischemic stress. (C) 2013 Elsevier Inc. All rights reserved.”
“Using biological markers to objectively measure addiction severity or to identify individuals who might benefit most from pro-cognitive treatment could

potentially revolutionize neuropsychopharmacology. We investigated the use of dopamine selleckchem receptor mRNA levels in circulating blood cells as predictors of cognitive response following dopamine agonist treatment, and as biomarkers of the severity of stimulant drug dependence.

We employed a double-blind, placebo-controlled cross-over design, administering a single dose of the selective dopamine D(2/3) receptor agonist pramipexole (0.5 mg) to increase dopamine transmission in one session and a placebo treatment in another session in 36 volunteers. Half the volunteers had a formal diagnosis of stimulant dependence, while half had no

psychiatric history. Participants performed neurocognitive tests from the CANTAB battery on both occasions, and stimulant-dependent individuals rated drug craving using visual analog scales. Whole-blood ISRIB mouse mRNA levels were measured for three dopamine-related genes: DRD3 and DRD4 (dopamine receptors), and catechol-O-methyltransferase (COMT; a dopamine catabolic enzyme).

Stimulant users performed worse than healthy volunteers on the cognitive tests. The variation in peripheral dopamine D(3) receptor mRNA expression explained over one quarter of the variation in response to pramipexole on the spatial working memory test across all participants. The severity of stimulant dependence was also significantly associated with peripheral COMT mRNA expression in stimulant users.

Peripheral expression of dopamine-related genes may be useful as a biomarker of cognitive response to dopamine agonist drugs and of severity of addiction to dopamine-releasing stimulant drugs.