Selenium deficiency triggering intractable seizures

Two children with severe neurodevelopmental retardation and elevated liver function tests developed intractable seizures during the first year of life. Detectable neurometabolic conditions have been ruled out. At the time of seizures evidence for systemic selenium deficiency could be documented. The youngest patient, who manifested intractable fits from the fourth day of life, died at the age of ten months. Neuropathologic examination was consistent with Progressive Neuronal Degeneration of Childhood (PNDC) with liver disease or formerly known as Alpers disease. In the oldest child, whose diet was normally balanced, fits started from the age of 11 months and features of long-standing selenium deficiency became apparent from the age of 1 1/2 years and consisted of liver function disturbances, depigmented hair and osteoarthropathy. Oral substitution with selenium supplements in both children (3-5 micrograms/kg body weight) resulted in reduction of seizures and improvement of the EEG recordings after two weeks while liver function became normal. Two of the seleno-dependent enzymes Glutathione Peroxidase (GPX) and Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPX) are speculated to play a key-role in the defence of neuronal cells against oxygen radical formation and peroxidative processes. Our findings support the hypothesis that the presence of selenium depletion in the brain amongst patients with epilepsy constitutes an important triggering factor for the origin of intractable seizures and subsequent neuronal damage

Stereoselective, Temperature-Dependent [2+2] Cycloaddition of N,N-Dialkylhydrazones to N-Benzyl-N-(benzyloxycarbonyl)aminoketene

13 páginas, 1 figura, 3 tablas, 9 esquemas.The Staudinger-like [2+2] cycloaddition of aliphatic hydrazones derived from (2R,5R)-1-amino-2,5-dimethylpyrrolidine to N-benzyl-N-(benzyloxycarbonyl)aminoketene takes place to afford the corresponding β-lactams in good yields when iPr2EtN is used as the base. The reaction proceeds in all cases with excellent stereocontrol to afford exclusively products having the (3R) configuration. Temperature was observed to exert a strong influence on the cis/trans selectivity, allowing in most cases the obtention of single trans or cis cycloadducts simply by performing the reactions at 80 °C or room temperature, respectively. Additional experiments support the hypothesis that the observed stereochemistry is the result of C=N isomerization in the zwitterionic intermediate, which takes place by a nucleophilic addition―rotation―elimination mechanism effected by the nucleophiles present in the reaction medium. Release of the dialkylamino group by oxidative cleavage of the N–N bond affords valuable compounds such as α,β-diamino acids and the azetidinone cores of monobactam antibiotics such as aztreonam and carumonam.We thank the Spanish Ministerio de Ciencia y Tecnología (MCYT) (CTQ2007-61915, CTQ2007-600244, and CTQ2004-00241) and the Junta de Andalucía (2005/FQM-658) for financial support. E. M.-L. thanks the Ministerio de Educación y Ciencia (MEC) for a predoctoral fellowship.Peer reviewe