BGP-15, a hydroximic acid derivative, protects against cisplatin- or taxol-induced peripheral neuropathy in rats.

The neuroprotective effect of BGP-15 against peripheral sensory neuropathy was studied in rats that were exposed to short-term cisplatin or taxol administration. The changes of nerve conduction velocity were determined in situ after treating the Wistar rats with BGP-15 (50, 100, and 200 mg/kg po daily doses throughout the experiment), cisplatin (1.5 mg/kg ip daily dose for 5 days), or taxol (5.0 mg/kg ip daily dose every other day in a 10-day interval) alone or giving the test compound in combination with cisplatin or taxol. Electrophysiological recordings were carried out in vivo by stimulating the sciatic nerve at both sciatic notch and ankle site. Neither motor nor sensory nerve conduction velocity was altered by any dose level of BGP-15 tested. Both anticancer drugs decreased the sensory nerve conduction velocity (SNCV). BGP-15 treatment prevented the impairment of SNCV either in part or totally in the cisplatin- or taxol-treated groups. This neuroprotective potential of BGP-15 could be well correlated with its recently described poly(ADP-ribose) polymerase- inhibitory effect and its ability to protect against the damages induced by the increased level of reactive oxygen species in response to anticancer treatment.

Impaired bronchomotor responses to field stimulation in guinea-pigs with cisplatin-induced neuropathy.

Pre-treatment with cisplatin (3 mg/kg) i.p. once a day over 6 days induced sensory neuropathy as confirmed by femoral nerve conduction velocity test and significantly decreased contractions induced by electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) in isolated main bronchial rings from guinea-pigs. The field stimulation-induced non-adrenergic, non-cholinergic (NANC) relaxations, however, were amplified in rings from animals with cisplatin neuropathy. The NANC relaxation response was completely blocked by 30 microM N(G)-nitro-L-arginine methyl ester in preparations from both control and cisplatin-treated animals. Superoxide dismutase (40 units/ml) was without effect on NANC relaxation in control rings, however, it substantially decreased NANC relaxation in preparations from animals with cisplatin neuropathy. These results show that cisplatin-induced sensory neuropathy is accompanied by attenuation of neural bronchoconstriction and an enhanced NANC relaxation. The latter is in part attained by an increased peripheral superoxide production.

The acute effect of ajmaline on ventricular arrhythmia after cardiac surgery.

The acute effect of ajmaline was investigated in the treatment of postoperative ventricular arrhythmias. Ajmaline (Glurytmal--Giulini Pharma GMBH) was applied intravenously in 15 patients suffering from ventricular premature beats (Lown II--IV/b), tachycardia and/or ventricular fibrillation after open heart surgery. Ajmaline infusion produced in 40% of the cases a total suppression and in 100% a significant improvement of malignant ventricular arrhythmia. In patients with recurrent and resistant ventricular tachycardia, ajmaline proved effective even when other antiarrhythmic drugs had failed. It was shown to be effective in reducing ventricular premature contractions and recurrent ventricular tachycardia after heart surgery, without haemodynamic side effects. Because of recurrent ventricular premature beats in 11 patients after acute ajmaline administration further oral application of prajmalium bitartarate (Neo-Gilurytmal) was necessary. The maintenance of these patients on oral ajmaline treatment seemed important.

Impact of neonatal treatment with cardioactive glycosides (digoxin, ouabain) on receptor binding capacity, blood level and cardiac function in the adult rat. Extension of the imprinting theory.

A single neonatal treatment with a cardioactive glycoside (ouabain, digoxin) altered the response of the adult rat to digitaloid treatment. As demonstrated by RIA, re-exposure to digoxin at 2 months of age was followed within 30 min by a more than twofold increase in serum digoxin over the not pretreated control and, although a steady concentration decrease followed, the experimental rats still had a higher serum digoxin level than the controls at 4 h. In the not presensitized control group the serum digoxin peak appeared at 60 min at a considerably lower level than the 30-min maximum of the experimental rats. Neonatal pretreatment with ouabain depressed myocardial ouabain binding, but enhanced the Na+ K+ -ATPase activity. The above differences were conspicuous in the functional response, yet a greater atrial response to the positive inotropic action of K-strophanthoside and a greater ventricular response to beta adrenergic excitation were readily seen in the experimental group. It follows that not only hormones, but also other ligands acting at receptor level can be regarded as potential inducers of imprinting.