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Biomedical subjects

N Kariv

Publications and source records attributed to N Kariv.

41 records · Page 3Linked to original sources
PubMed1980

A preclinical study of EO-122, a new lidocaine-like antiarrhythmic drug.

The 2,6-dimethylanilide of quinuclidine-3-carboxylic acid hydrochloride (EO-122), a new structural analog of lidocaine, has been shown to possess potent antiarrhythmic activity in experimentally induced arrhythmias in animals. Restoration of normal sinus rhythm and suppression of ouabain-induced arrhythmia in cats and dogs, and of coronary occlusion-induced arrhythmia in dogs, followed a single IV injection of 1--3 mg/kg, with an onset of 2 minutes and a duration of 20--240 minutes. Occlusion-induced arrhythmia was likewise suppressed after an oral dose of 10--20 mg/kg, with an onset of 11--65 minutes and a duration of 25--120 minutes. Under similar conditions, lidocaine was either totally ineffective or of ultra-short duration. The bioavailability of EO0122 by the oral route exceeded 80% of the oral dose. Therapeutic blood concentrations were in the range 0.5--7 microgram/ml. At about 5 microgram/ml there was a slight depression of cardiac function in the anesthetized cat, but not in the conscious dog. In cats, complete A-V block occurred at concentrations of 60--70 microgram/ml. The IV LD50 in mice was 22 mg/kg, and in rabbits 8.5 mg/kg. No overt signs of neurotoxicity could be observed at any dose of EO-122. The pharmacokinetic profile of the drug fits a two-compartment open model, with t1/2 congruent to 150 min and Vd (SS) congruent to 1.5 l/kg.

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PubMed1980

Effect of addition of 10% Amberlite XAD-2 to the diet on serum cholesterol and atherogenesis in rabbits.

The effects of addition of the polystyrene resin XAD-2 to the diet of rabbits on serum cholesterol, on hepatic enzyme of cholesterol synthesis (HMG-CoA reductase), and on atherogenesis was determined. Feeding of XAD-2 caused substantial decrease of total serum cholesterol and of the cholesterol of the apo B-containing lipoproteins (50%). Atherogenesis, which was induced by mechanical injury to the arterial wall, greatly decreased (p < 0.01) in animals fed with 10% XAD-2 supplement in their diet. Average lesions volume of 4.2 +/- 2.0 mm3 per aorta was observed in animals maintained on XAD-2 diet, in comparison to 15.42 +/- 3.3 mm3 in animals maintained on regular diet. The animals maintained on XAD-2 showed elevated activity of hepatic HMG-CoA reductase. The activity of this enzyme was 3.2 fold that obtained from livers of control animals.

Animals↗
PubMedDate not supplied

Indomethacin inhibits the accumulation of tumor cells in mouse lungs and subsequent growth of lung metastases.

BACKGROUND: The interaction of cancer cells with blood cells and cell wall components evokes inflammatory responses and is a critical event in the metastatic process. Indomethacin is a potent inhibitor of the cyclooxygenase (COX) enzymes and has previously been shown to decrease the growth of primary tumors in vivo. Proinflammatory prostaglandins produced by the two COX enzymes may also play a role in the development of metastases. METHODS: To directly address this question, we tested the effect of indomethacin on the accumulation of circulating [(3)H]-uridine-labeled tumor cells in the lungs and on the subsequent development of lung tumors. RESULTS: We found that inhibition of COX activity in the recipient mice prior to the injection of tumor cells decreased the percentage of the cells arrested in the lungs. This effect was highly significant since it subsequently led to substantial attenuation of lung metastasis development. CONCLUSION: These data thus demonstrate the antimetastatic effect of indomethacin through a mechanism which involves a reduction in tumor cell uptake by the lungs.

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