Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individual Escherichia coli strains produce several cell surface polysaccharides. In E. coli E69, the his region of the chromosome contains the rfb (serotype O9 lipopolysaccharide O-antigen biosynthesis) and cps (serotype K30 group IA capsular polysaccharide biosynthesis) loci. Polymorphisms in this region of the Escherichia coli chromosome reflect extensive antigenic diversity in the species. Previously, we reported a duplication of the manC-manB genes, encoding enzymes involved in GDP-mannose formation, upstream of rfb in strain E69 (P. Jayaratne et al., J. Bacteriol. 176:3126-3139, 1994). Here we show that one of the manC-manB copies is flanked by IS1 elements, providing a potential mechanism for the gene duplication. Adjacent to manB1 on the IS1-flanked segment is a further open reading frame (ugd), encoding uridine-5'-diphosphoglucose dehydrogenase. The Ugd enzyme is responsible for the production of UDP-glucuronic acid, a precursor required for K30 antigen synthesis. Construction of a chromosomal ugd::Gm(r) insertion mutation demonstrated the essential role for Ugd in the biosynthesis of the K30 antigen and confirmed that there is no additional functional ugd copy in strain E69. PCR amplification and Southern hybridization were used to examine the distribution of IS1 elements and ugd genes in the vicinity of rfb in other E. coli strains, producing different group IA K antigens. The relative order of genes and, where present, IS1 elements was established in these strains. The regions adjacent to rfb in these strains are highly variable in both size and gene order, but in all cases where a ugd homolog was present, it was found near rfb. The presence of IS1 elements in the rfb regions of several of these strains provides a potential mechanism for recombination and deletion events which could contribute to the antigenic diversity seen in surface polysaccharides.
 ...
PMID:Polymorphism, duplication, and IS1-mediated rearrangement in the chromosomal his-rfb-gnd region of Escherichia coli strains with group IA and capsular K antigens. 915 Feb 18

During the period 1989-2009, 14 new antiepileptic drugs (AEDs) were licensed for clinical use and these can be subdivided into new second- and third-generation AEDs. The second-generation AEDs comprise felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. The third-generation AEDs comprise eslicarbazepine acetate and lacosamide. The interaction propensity of AEDs is very important because all new AEDs are licensed, at least in the first instance, as adjunctive therapy. The present review summarizes the interactions (pharmacokinetic and pharmacodynamic) that have been reported with the newer AEDs. The pharmacokinetic interactions include those relating to protein-binding displacement from albumin in blood, and metabolic inhibitory and induction interactions occurring in the liver. Overall, the newer AEDs are less interacting because their pharmacokinetics are more favorable and many are minimally or not bound to blood albumin (e.g., eslicarbazepine, felbamate, gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) and are primarily renally excreted or metabolized by noncytochrome P450 or uridine glucoronyl transferases (e.g., gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) as opposed to hepatic metabolism which is particularly amenable to interference. Gabapentin, lacosamide, levetiracetam, pregabalin and vigabatrin are essentially not associated with clinically significant pharmacokinetic interactions. Of the new AEDs, lamotrigine and topiramate are the most interacting. Furthermore, the metabolism of lamotrigine is susceptible to both enzyme inhibition and enzyme induction. While the metabolism of felbamate, tiagabine, topiramate and zonisamide can be induced by enzyme-inducing AEDs, they are less vulnerable to inhibition by valproate. Noteworthy is the fact that only five new AEDs (eslicarbazepine, felbamate, oxcarbazepine, rufinamide and topiramate) interact with oral contraceptives and compromise contraception control. The most clinically significant pharmacodynamic interaction is that relating to the synergism of valproate and lamotrigine for complex partial seizures. Compared with the first-generation AEDs, the new second- and third-generation AEDs are less interacting, and this is a desirable development because it allows ease of prescribing by the physician and less complicated therapeutic outcomes and complications for patients.
 ...
PMID:Drug interactions involving the new second- and third-generation antiepileptic drugs. 2002 26