1,721,287 research outputs found
Toxic effects of cobalt in primary cultures of mouse astrocytes. Similarities with hypoxia and role of HIF-1alpha
No full textCobalt is suspected to cause memory deficit in humans and was reported to induce neurotoxicity in animal models. We have studied the effects of cobalt in primary cultures of mouse astrocytes. CoCl2 (0.2-0.8 mM) caused dose-dependent ATP depletion, apoptosis (cell shrinkage, phosphatidylserine externalization and chromatin rearrangements) and secondary necrosis. The mitochondria appeared to be a main target of cobalt toxicity, as shown by the loss of mitochondrial membrane potential (ΔΨm) and release from the mitochondria of apoptogenic factors, e.g. apoptosis inducing factor (AIF). Pre-treatment with bongkrekic acid reduced ATP depletion, implicating the involvement of the mitochondrial permeability transition (MPT) pore. Cobalt increased the generation of oxygen radicals, but antioxidants did not prevent toxicity. There was also an impaired response to ATP stimulation, evaluated as a lower raise in intracellular calcium. Similarly to hypoxia and dymethyloxallyl glycine (DMOG), cobalt triggered stabilization of the α-subunit of hypoxia-inducible factor HIF-1 (HIF-1α). This early event was followed by an increased expression of HIF-1 regulated genes, e.g. stress protein HO-1, pro-apoptotic factor Nip3 and iNOS. Although all of the three stimuli activated the HIF-1α pathway and decreased ATP levels, the downstream effects were different. DMOG only inhibited cell proliferation, whereas the other two conditions caused cell death by apoptosis and necrosis. This points to cobalt and hypoxia not only inducing HIF-1α regulated genes but also affecting similarly other cellular functions, including metabolism. © 2006 Elsevier Inc. All rights reserved
Adenosine, adenosine A2A antagonists, and Parkinson's disease
No full textAdenosine derived from the degradation of ATP/AMP functions as a signalling molecule in the nervous system through the occupation of A1, A2, and A3 adenosine receptors. Adenosine A2A receptors have a selective localization to the basal ganglia and specifically to the indirect output pathway, and as a consequence offer a unique opportunity to modulate the output from the striatum that is believed critical to the occurrence of motor components of PD. Indeed, the ability of A2A antagonists to modulate basal ganglia neurotransmission has been shown to be associated with improved motor function in experimental models of PD. This suggests that A2A antagonists would be effective as a symptomatic treatment in humans without provoking marked dyskinesia. Indeed, the A2A antagonist istradefylline reduces OFF time in moderate- to late-stage patients with PD already receiving dopaminergic therapy, with an increase in non-troublesome dyskinesia. Adenosine and adenosine receptors also exert actions relevant to pathogenesis in PD, raising the possibility of their use as neuroprotective agents. Both epidemiologic evidence and the current preclinical data strongly support a role for A2A antagonists in protecting dopaminergic neurons and influencing the onset and progression of P
RELEASE OF TWO VASODILATORS, ADENOSINE AND PROSTACYCLIN, FROM ISOLATED RABBIT HEARTS DURING CONTROLLED HYPOXIA.
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Adenosine and neuroprotection
No full textIn summary, there is good evidence that adenosine is an endogenous neuroprotective agent. Probably several mechanisms can contribute to this effect and the relative importance of these mechanisms may depend on the type of ischaemia. There is also evidence that drugs that affect adenosine may be used therapeutically. An important caveat is that acute and long-term effects of adenosine receptor agonists and antagonists differ widely. This effect inversion suggests that drugs that affect adenosine receptors also induce important adaptive events in the central nervous system. Such adaptive effects may also be evident in the case of other agents, which emphasizes that the long-term usefulness of a therapeutic strategy cannot always be judged only from acute studies
- …
