Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enoxacin is a second-generation quinolone derivative recently introduced in Spain. Its activity comes through the inhibition of bacterial DNA-gyrase and it has a good antibacterial capacity against a broad spectrum of gram-positive and gram-negative bacteria. It is presumed to be less toxic than the rest of the quinolones and its use is increasing, specially to treat infections of the urogenital tract. Cases of photosensitivity to enoxacin have been very rarely reported. We describe 2 patients with photosensitivity reactions due to this drug.
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PMID:Enoxacin-induced photosensitivity: study of two cases. 148 23

Cells from patients with Bloom syndrome, a cancer-prone disorder with cutaneous photosensitivity and spontaneous chromosome breakage, exhibit an abnormally increased number of sister-chromatid exchanges following treatment with 5-bromodeoxyuridine (BrdU). This effect has been postulated to be mediated by abnormal topoisomerase II activity. We used alkaline elution to measure DNA single-strand breakage following prolonged exposure to BrdU. Five-day exposure to BrdU produced equal numbers of alkali-labile sites in normal and Bloom-syndrome fibroblasts. These breaks were not protein-associated but were produced by alkali. Treatment with topoisomerase II inhibitors induced similar frequencies of DNA single-strand breaks in normal and Bloom-syndrome fibroblasts. These findings imply that BrdU incorporation into cellular DNA induces alkali-labile DNA lesions that are independent of topoisomerase II activity in Bloom and normal cells.
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PMID:Relationship of DNA strand breakage produced by bromodeoxyuridine to topoisomerase II activity in Bloom-syndrome fibroblasts. 184 52

The recent piperazinyl-substituted mono-fluoroquinolones represent a family with some common characteristics on one side, and variable parameters on the other side. COMMON characteristics: same mechanism of action: DNA-gyrase inhibitors of the A subunit of topoisomerase; pH dependent antibacterial activity; a rather long post-antibiotic effect for both gram-positive and gram-negative bacteria; same physiochemical properties: organic acids, high pKa, lipophilicity. Some common pharmacokinetic parameters: low protein binding (less than 50%); high volume of distribution (greater than 1.5 l/kg) with good attainable tissue concentrations in lymph, blister fluid, renal tissue, prostate, bronchial secretions, saliva, aqueous humor, CSF, bone, bile; good intracellular penetration in macrophages, polynuclear neutrophils; high peak urinary concentrations markedly exceeding the MIC for virtually all bacterial urinary tract pathogens, even accounting for the increase in MIC in the urine, especially at lower (acidic) pH; low extraction ratio dialysis; similar adverse reactions; CNS, gastro-intestinal, photosensitivity, tendo-articular and cartilage toxicity. However, most other pharmacokinetic parameters are different from one fluoroquinolone to the other; oral bioavailability, peak serum levels (C max) as a measure of bioavailability, terminal half-life of elimination (t1/2) are all variable. The extent of metabolic biotransformation varies greatly, the two extremes being ofloxacin, showing a high metabolic stability, and pefloxacin, highly metabolized. The degree of antibacterial activity of different metabolites also varies greatly. The renal clearance of most fluoroquinolones, except pefloxacin, greatly exceeds normal glomerular filtration rate, suggesting additional renal tubular secretion. Renal elimination of most fluoroquinolones - except pefloxacin, is blocked by probenecid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative pharmacokinetic parameters of new systemic fluoroquinolones: a review. 329 63

The recent piperazinyl-substituted mono-fluoroquinolones represent a family with some common features on the one hand, and some variable parameters on the other. Some of the common features are: same mechanism of action (DNA-gyrase inhibitors of the A subunit of topoisomerase); pH-dependent antibacterial activity; a rather long post-antibiotic effect for both Gram-positive and Gram-negative bacteria; same physicochemical properties (organic acids, high pKa, lipophilicity). Common pharmacokinetic parameters include low protein binding (less than 50%); high volume of distribution (greater than 1 l/kg) with good tissue concentrations attainable in lymph, blister fluid, renal tissue prostate, bronchial secretions, saliva, aqueous humour, CSF, bone and bile; good intracellular penetration in macrophages and polynuclear neutrophils; high peak urinary concentrations, markedly exceeding the MIC for virtually all bacterial urinary tract pathogens, even accounting for the increase in MIC in the urine, especially at lower (acidic) pH; low extraction ratio dialysis; similar adverse reactions (CNS, gastrointestinal, photosensitivity, tendo-articular and cartilage toxicity). However, most other pharmacokinetic parameters are different from one fluoroquinolone to the other: oral bioavailability, peak serum levels (Cmax) as a measure of bioavailability, terminal half-life of elimination (t1/2) are all variable. The extent of metabolic biotransformation varies greatly, the two extremes being ofloxacin, showing a high metabolic stability and pefloxacin, highly metabolized. The degree of antibacterial activity of different metabolites also varies widely.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative pharmacokinetic parameters of new systemic fluoroquinolones. 329 83