20 research outputs found
Administration of Thimerosal to Infant Rats Increases Overflow of Glutamate and Aspartate in the Prefrontal Cortex: Protective Role of Dehydroepiandrosterone Sulfate
Thimerosal, a mercury-containing vaccine preservative, is a suspected factor in the etiology of neurodevelopmental disorders. We previously showed that its administration to infant rats causes behavioral, neurochemical and neuropathological abnormalities similar to those present in autism. Here we examined, using microdialysis, the effect of thimerosal on extracellular levels of neuroactive amino acids in the rat prefrontal cortex (PFC). Thimerosal administration (4 injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15) induced lasting changes in amino acid overflow: an increase of glutamate and aspartate accompanied by a decrease of glycine and alanine; measured 10–14 weeks after the injections. Four injections of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate and aspartate concentrations at microdialysis time (but based on thimerosal pharmacokinetics, could have been effective soon after its injection). Application of thimerosal to the PFC in perfusion fluid evoked a rapid increase of glutamate overflow. Coadministration of the neurosteroid, dehydroepiandrosterone sulfate (DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate and aspartate; the steroid alone had no influence on these amino acids. Coapplication of DHEAS with thimerosal in perfusion fluid also blocked the acute action of thimerosal on glutamate. In contrast, DHEAS alone reduced overflow of glycine and alanine, somewhat potentiating the thimerosal effect on these amino acids. Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders. DHEAS may partially protect against mercurials-induced neurotoxicity
A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction
Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acidinduced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5dihydroxybenzoic acid to a range of 2,5substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholineinduced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF2 and H2DCFDA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RTPCR and western blotting were utilized to measure Akt, eNOS, Nrf2, NQO1 and HO1 expression. Results: Ex vivo endotheliumdependent relaxation was significantly improved by the glycomimetics under palmitateinduced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitateinduced oxidative stress and enhanced NO production. We demonstrate that the protective effects of preincubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROSinduced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease
Isotope ratio measurements of Mo, V, Ti, and Zr and the determination of these elements in water samples with a thermal ionization quadrupole mass spectrometer
Vibrational spectroscopic and electrochemical characteristics of poly (propylene glycol)-silver triflate polymer electrolyte system
Unlocking the energy capabilities of micron-sized LiFePO4
Utilization of LiFePO4 as a cathode material for Li-ion batteries often requires size nanonization coupled with calcination-based carbon coating to improve its electrochemical performance, which, however, is usually at the expense of tap density and may be environmentally problematic. Here we report the utilization of micron-sized LiFePO4, which has a higher tap density than its nano-sized siblings, by forming a conducting polymer coating on its surface with a greener diazonium chemistry. Specifically, micron-sized LiFePO4 particles have been uniformly coated with a thin polyphenylene film via the spontaneous reaction between LiFePO4 and an aromatic diazonium salt of benzenediazonium tetrafluoroborate. The coated micron-sized LiFePO4, compared with its pristine counterpart, has shown improved electrical conductivity, high rate capability and excellent cyclability when used as a 'carbon additive free' cathode material for rechargeable Li-ion batteries. The bonding mechanism of polyphenylene to LiFePO4/FePO4 has been understood with density functional theory calculations.'Strategic Priority Research Program' of the Chinese Academy of Sciences [XDA09010401]; 'the Recruitment Program of Global Youth Experts' of China; 'Science and Technology Development Program' of Jilin Province [20150623002TC]; National Natural Science Foundation of China [21190040]; US National Science Foundation (US-NSF) under the NSF EPSCoR [EPS-1003897]; Louisiana Board of Regents; US-NSFSCI(E)[email protected]; [email protected]; [email protected]