Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the feasibility of intrathecal perfusion of ACNU (3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitro sou rea hydrochloride) in the treatment of subarachnoid dissemination of malignant glioma, the neurotoxicity and pharmacokinetics of ACNU were studied in dogs. ACNU [1-2 mg dissolved in 10-20 ml of lactated Ringer's solution or artificial cerebrospinal fluid (CSF)] was administered via the right lateral ventricle by constant drip infusion and CSF was drained by lumbar puncture. The infusion time was from 15 to 71 min. For the control, a bolus injection was given. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord revealed only mild denudation of ependyma in the wall of the ventricles in a dog treated three times with 2 mg ACNU (perfusion twice, bolus injection once) and in 2 dogs perfused with 1 mg ACNU once a week for 10 weeks. ACNU was not detected in lumbar CSF after bolus injection into the lateral ventricle. When 1 mg of ACNU, dissolved in 10 ml of artificial CSF, was perfused for a duration of 22 to 31 min, it started to appear in the lumbar CSF 10 to 15 min after the start of perfusion, reaching a maximum concentration of 13.88 to 22.31 micrograms/ml. The area under the drug concentration-time curve was 344 to 706 micrograms x min/ml; the half-time was 15.5 to 19.5 min. The distribution volume was 30.6 to 54.1 ml. These findings suggest the feasibility of intrathecal perfusion of ACNU in the treatment of patients with subarachnoid dissemination of glioma.
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PMID:Neurotoxicity and pharmacokinetics of intrathecal perfusion of ACNU in dogs. 233 7

1. The aim of this study was to elucidate if the K+ uptake was higher in cultured human glioma cells than in cells from other malignant tumors and to analyze the importance of membrane potential and K+ channels for the uptake. 2. K+ transport properties were studied with the isotopes 42K and the K-analogue 201Tl. 3. Comparison with cultured cells from other malignant tumors showed that the specific steady-state accumulation of Tl+ was significantly higher in glioma cells (U-251MG and Tp-378MG). 4. In Ringer's solution at 37 degrees C the rates of K+ and Tl+ uptake were both inhibited by about 55% in ouabain and 60% in furosemide, bumetanide, or Na(+)- or Cl(-)-free medium. This indicated that the routes for K+ and Tl+ uptake were similar and due to Na,K-ATPase-dependent transport and to Na-K-Cl cotransport. 5. About 10% of the uptake was neither ouabain nor bumetanide sensitive. Ba2+, which is known to block inward-rectifying K+ channels and to depolarize glial cells, and other K+ channel blockers (Cs+ and bupivacaine), had no effect on Tl+ uptake. 6. Metabolic inhibition with dinitrophenol reduced the uptake rate to 17%. 7. The washout of Tl+ was unaffected by bumetanide and K+ channel blockers, but dinitrophenol caused a transient increase of 75%, an effect which persisted in the presence of K+ channel blockers. 8. It was concluded that the high specific K+ and Tl+ accumulation in cultured human glioma cells was due not to the presence of inwardly rectifying K+ channels or other identified K+ channels, but to Na,K-ATPase dependent transport and Na-K-Cl cotransport.
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PMID:Mechanism of high K+ and Tl+ uptake in cultured human glioma cells. 755 34