Previous neuron and glial cell culture studies of excessive poly (ADP-ribose) polymerase (PARP-1) activation found NAD + depletion, glycolytic arrest, and cell death that could be avoided by exogenous tricarboxylic acid cycle (TCA) metabolites, especially pyruvate (pyr). Pyruvate neuroprotection has been attributed to cytosolic NAD + replenishment, TCA metabolism, and antioxidant activity. We investigated the first two mechanisms in respiring cerebrocortical slices after a 1-h H 2 O 2 exposure to activate PARP-1. H 2 O 2 was followed by a 4-h recovery with oxy-artificial cerebrospinal fluid superfusion having either: (1) no glucose (glc) or pyruvate; (2) 10 mmol/L glc only; (3) 10 mmol/L pyruvate only; (4) both 10 mmol/L glc and 10 mmol/L pyruvate. Poly-ADPribosylation was quantified from Western blots and immunohistochemistry. Perchloric acid extracts were quantified with 14.1 T 31 P nuclear magnetic resonance spectroscopy. Just after H 2 O 2 exposure, ATP and NAD + decreased by E50%, PCr decreased by 75%, and the ADP/ATP ratio approximately doubled. ATP and NAD + changes, but not PCr changes, were nearly eliminated if PARP inhibitors accompanied the H 2 O 2 . Recovery with both pyruvate and glc was better than with glc alone, having higher ATP (0.161 versus 0.075, P < 0.01) and PCr levels (0.144 versus 0.078, P < 0.01), and higher viable cell counts in TUNEL and Fluoro-Jade B staining. Two-dimensional [ 1 H-13 C] HSQC spectra showed metabolism during recovery of 13 C glc or pyr. Pyruvate metabolism was primarily via pyruvate dehydrogenase, with some via pyruvate carboxylation. Pyruvate superfusion of PARPinjured brain slices helps replenish NAD + while providing metabolic fuel. Although this augments recovery, a strong antioxidant role for pyruvate has not been ruled out.
Summary: A patient with Williams syndrome, craniosynostosis, and infantile spasms is described. At age 6 months, the infant demonstrated infantile spasms and craniosynostosis and was operated on for craniosynostosis and treated with adrenocorticotropic hormone (ACTH) for the infantile spasms. ACTH completely controlled the seizures, but was halted because of the progression of ventricular hypertrophy. The seizure returned, and he was found to have elfin face, failure‐to‐thrive, developmental delay, and dental malformation in addition to congenital heart defects. High‐resolution chromosome analysis revealed interstitial deletion of 7q11.22‐q11.23. Therefore his clinical and cytogenetic diagnosis was Williams syndrome. Thyrotropin‐releasing hormone (TRH) therapy reduced his seizures and improved the findings of EEG without cardiac side effects. In addition, his psychomotor development was slightly improved.
Lithium ion conducting glasses were prepared in the system (0.6Li2S•E0.4SiS2)-Li3PO4 by twin-roller rapid quenching. The temperatures of glass transition (Tg) and crystallization (Tc) were determined for the glassy samples with 0-40mol% Li3PO4. The conductivity values at 25•Ž (ƒÐ25) were maximized and the activation energies (Ea) for conduction were minimized at the composition with 5mol% Li3PO4; the maximum ƒÐ25 value was as high as 9•~10-4S•Ecm-1. Since the differ ence between Tg and Tc was also maximized at the same composition, it was concluded that the doping of small amounts of Li3PO4 improved both the glass stabil ity against crystallization and the lithium ion conduc tivities.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.