Monastryl blue and triphenyl tetrazolium chloride staining were used to assess size of the areas at risk and infarction. Glycogen content was assessed using periodic acid-Schiff staining. Cell death and survival signaling pathways were assessed by immunoblotting.
Results: Serine/threonin kinase inhibitor Mean arterial pressure and developed left ventricular pressure were lower in the DM group (P < .05).
Whereas global left ventricular function was worse in the DM group (P < .05), regional function in the area at risk was improved on the horizontal axis (P < .05). Mean infarct size was smaller in the DM versus the ND group (19% vs 43%; P < .05), whereas the area at risk was similar in both groups (34% vs 36%; P = .7). Ischemic myocardium in the DM group displayed more prominent staining for glycogen compared with the ND group. In the area at risk, expression of
cell survival proteins including phosphorylated endothelial nitric oxide synthase (0.17 +/- 0.04 vs 0.04 +/- 0.01; P < .05), heat shock protein 27 (0.7 +/- 0.2 vs 0.3 +/- 0.1; P < .05), nuclear factor-kappa B (0.14 +/- 0.02 vs 0.03 +/- 0.01; P < .05), and mammalian target of rapamycin (0.35 +/- 0.05 vs 0.15 +/- 0.02; P < .05) were higher in DM animals, whereas in nonischemic tissue, expression of these proteins was similar or lower in the DM group.
Conclusions: Although type I diabetes worsens global left ventricular function, it is protective in the ischemic area, leading selleck products to increased expression of cell survival proteins and decreased infarct size. (J Thorac Cardiovasc Surg 2010;140:1345-52)”
“Zn2+ is co-released at glutamatergic synapses throughout the central nervous system and acts as a neuromodulator for glutamatergic neurotransmission, as a key modulator of NMDA receptor
functioning. Zn2+ is also implicated in the neurotoxicity associated with several models of acute brain injury and neurodegeneration. SHP099 Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons in the spinal cord and cortex. In this study, we have investigated the modulatory role exerted by Zn2+ in NMDA-mediated neurotoxicity in either near-pure or mixed cortical cultured neurons obtained from either mice over-expressing the G93A mutant form of Cu/Zn superoxide dismutase (SOD1) human gene, a gene linked to familial ALS, or wild type (WT) mice. To that aim, SOD1(G93A) or WT cultures were exposed to either NMDA by itself or to Zn2+ prior to a toxic challenge with NMDA, and neuronal loss evaluated 24 h later. While we failed to observe any significant difference between NMDA and Zn2+/NMDA-mediated toxicity in mixed SOD1(G93A) or WT cortical cultures, different vulnerability to these toxic paradigms was found in near-pure neuronal cultures. In the WT near-pure neuronal cultures, a brief exposure to sublethal concentrations of Zn2+-enhanced NMDA receptor-mediated cell death, an effect that was far more pronounced in the SOD1(G93A) cultures.