Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study begins to explore possible mechanisms underlying the role of GABAB receptors in absence seizures in lethargic (lh/lh) mice. To test the hypothesis that alterations intrinsic to the GABAB receptor underlie enhanced synaptic activation of these receptors in absence seizures, we measured GABA-displaceable [3H]baclofen binding to neocortical plasma membranes prepared from lh/lh and wild (+/+) age-matched congenic mice. The number (Bmax) of binding sites was significantly greater (20%) in lh/lh (4.2 pmol/mg protein, n = 43 pairs, P < 0.02) than in +/+ mice (3.3 pmol/mg protein) in an age-independent manner. Interestingly, the subset of lh/lh mice with greater seizure frequency (40-70 seizures/15 min, measured by bipolar electrodes implanted into neocortex; n = 11) had a significantly greater Bmax (P < 0.003) than the subset with lower seizure frequency (1-10 seizures/15 min; n = 11). The equilibrium dissociation constant (Kd) was unchanged (60 nM in both). The Kd of both strains was inhibited to an equal degree by the nonhydrolysable GTP analogue 5'-guanylimido-diphosphate [Gpp(NH)p]. The increased number of GABAB binding sites was selective, because binding to NMDA sites ([3H]glutamate binding) and to GABAA sites ([3H]muscimol binding) was not significantly different in the two strains. These data suggest that the increased number of GABAB receptors in lh/lh mice underlies enhanced synaptic activation of these receptors. Together with evidence that GABAB receptor activation can produce disinhibition, our data support a role for GABAB receptors in the expression of absence seizures in lh/lh mice.
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PMID:Increased number of GABAB receptors in the lethargic (lh/lh) mouse model of absence epilepsy. 838 8

Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder due to a fundamental defect in the glycine cleavage system, which leads to neuronal dysfunction caused by two receptor-mediated mechanisms. It is a life-threatening condition in the neonate. Until now, the disease has not been described from Saudi Arabia. We report on three Saudi newborns (two males and one female) who had NKH. Two of these were siblings (male and female). Following uneventful deliveries, they presented between the first and third day of life with progressive lethargy, poor feeding, recurrent apnea and severe hypotonia. Two newborns had myoclonic seizures, whereas electroencephalogram showed burst-suppression pattern in all of them. The diagnosis was confirmed by high cerebrospinal fluid/plasma glycine ratio (0.2 and 1.08) in two patients (normal < 0.030, whereas a sibling of one of the neonates had a high glycine level. Both siblings died during the second month of life despite therapy with dextromethorphan (an N-methyl-D-asparate [NMDA] receptor antagonist) in one of them. The third day had ketamine (noncompetitive NMDA receptor antagonist) and sodium benzoate (that conjugates with glycine, forming nontoxic hippuric acid). Although his seizures were controlled, he survived with severe neurological sequelae.
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PMID:Nonketotic hyperglycinemia: A life-threatening disorder in Saudi newborns. 1737 75