Diurnal and seasonal changes in endogenous melatonin levels in the blood plasma in dogs.

This paper describes research on the levels of endogenous melatonin (MLT) in the blood serum in dogs in different seasons (March, June, September, December) and at different times of day (11:00, 12:00, 23:00, 24:00 and 1:00), using immunoassay method. Blood samples were collected in the diurnal cycle, in consecutive seasons. The conducted studies show that MLT levels undergo clear changes in both the diurnal cycle, as well as in seasonal one in this species.

The role of the serotonergic system in foot shock-induced behavior in mice.

In a foot shock-induced fighting (FSIF) test, serotonergic and antiserotonergic agents were examined. Stimulation of the brain 5-hydroxytryptamine (5-HT) neurons with different serotonergic agents, such as l-tryptophan, 5-hydroxytryptophan, imipramine, fluoxetine, 5-methoxy-tryptamine, quipazine, and fenfluramine, showed the inhibiting role of the 5-HT system in FSIF. At the same time, following the results obtained in FSIF tests and locomotor activity tests, it can be inferred that the 5-HT antagonists used (methysergide, cyproheptadine, metergoline, cinnarizine, and pizotifen) do not act specifically in this model of aggression. P-Chlorophenylalanine effects on mice in FSIF also seem to be partly due to catecholaminolytic action.

Influence of chronic aminophylline on antielectroshock activity of diazepam and aminophylline-induced convulsions in mice.

The effects of chronic administration of aminophylline (AMPH; 50 mg/kg, twice daily for 14 consecutive days) were studied on both antielectroshock efficacy of diazepam (DZP) and convulsive activity of AMPH in mice. AMPH injected acutely at a dose of 50 mg/kg significantly reduced anticonvulsant action of DZP elevating ED50 from 10.9 (control) to 15.9 mg/kg (p < 0.01). After the administration of AMPH for 3 days, ED50 value was still higher compared with control. Chronic treatment with AMPH resulted in further increase of ED50 of DZP, which was 20.2 mg/kg, and this elevation was significant not only when compared with saline-treated animals, but also with acute and 3-day administration of the xanthine (p < 0.01, 0.05, and 0.001, respectively). Therefore, no tolerance to this AMPH-mediated effect was found, and even an enhancing influence was observed. On the other hand, chronic treatment with AMPH decreased convulsive activity of AMPH elevating ED50 for induction of clonic seizures from 218 to 252 mg/kg (p < 0.01). The remaining seizure parameters were unaffected. Furthermore, in both cases pharmacokinetic interactions were excluded, at least in terms of total plasma levels of the drugs. The results suggest that the mechanisms governing AMPH-induced reversal of the anticonvulsant efficacy of DZP qualitatively differ from those underlying AMPH-induced convulsions. Moreover, these data support the claim that AMPH should be avoided in patients suffering from different types of epilepsy.

Pharmacokinetics of tylosin in broiler chickens.

Biological availability and pharmacokinetic properties of tylosin were determined in broiler chickens after oral (p.o.) and intravenous (i.v.) administration at a dose of 10 mg/kg. The calculated bioavailability--F%, by comparing AUC values--p.o. and AUC--i.v., ranged from 30%-34%. After intravenous injection tylosin was rapidly distributed in the organism, showing elimination half-life (t1/2 beta) values of 0.52 h and distribution volume (Vd) of 0.69 L/kg, at a clearance rate (Cl) of 5.30 +/- 0.59 ml/min/kg. After oral administration, tylosin has a similar distribution volume (Vd = 0.85 L/kg), while the elimination half-life t1/2 beta of 2.07 h was four times bigger than after i.v. administration at Cl = 4.40 +/- 0.27 ml/min/kg. The obtained value tmax = 1.5 h for tylosin after oral administration indicates that using this antibiotic with drinking water in broiler chickens is the method of choice. However, a relatively low value Cmax = 1.2 micrograms/ml after oral administration of tylosin shows that dosing of this antibiotic in broiler chickens should be higher than in other food producing animals.

Interspecies aggressiveness of rats towards mice after the application of p-chlorophenylalanine.

The administration of pCPA (400 mg/kg) induces in 30% of Wistar rats the potentiation of interspecies aggressiveness and develops in them the instinct to kill mice. It can be supposed that 5-HT system inhibits aggressive behaviour in this type of aggressiveness. Applying mouse killing test it has been stated that cholinergic receptor blockers (atropine, scopolamine) suppress the predatory instinct towards mice in killer rats and the pilocarpine, the cholinomimetic, develops such instinct in rats which previously did not kill mice. The results of the mouse killing test indicate that cholinergic system affects this type of aggressiveness in rats. For the time being, it is difficult to state the correlation between 5-HT and cholinergic system in this type of aggressive behaviour in rats.

The role of serotonergic and cholinergic systems in the aggression-stereotypy complex produced by amphetamine in mice.

The aggression--stereotypy complex (ASC) was produced in mice by administration of 15 mg/kg of amphetamine. The elevation of cerebral serotonin level in the mouse brain by administration of L-tryptophan or DL-5-hydroxytryptophan suppressed the aggressiveness without affecting significantly the stereotypy. Serotonin antagonists: methysergide and cyproheptadine, did not potentiate clearly the aggressive component of ASC. Cholinomimetics, pilocarpine and physostigmine, strongly suppressed the aggressive component, while a cholinolytic, scopolamine, evidently potentiated the elements of aggressive behavior. The aggressiveness observed in the ASC in the mouse receiving a large dose of amphetanine is predominantly dependent on the increase of activity of dopaminergic system, but seems to be functionally dependent also on the serotonergic and cholinergic systems.

Effect of GABA-ergic drugs on flunarizine-induced seizures in rabbits.

In this study the authors have evaluated the effects of common antiepileptic drugs given alone or in combinations with baclofen on seizures evoked by intravenous flunarizine in rabbits. The abolition of clonic and clonic-tonic convulsions was taken as the end point. Baclofen was able to inhibit convulsions only in a relatively high dose (5 mg/kg). Diazepam (1.5 mg/kg) and clonazepam (2 mg/kg) completely abolished clonic seizures. Valproate (20 mg/kg) inhibited clonic seizures and remained without effect on tonic convulsions. Other antiepileptics such as carbamazepine and acetazolamide were found inactive in this respect. Moreover, combinations of acetazolamide (100 mg/kg) and carbamazepine (50 mg/kg) with baclofen (2 mg/kg) had no anticonvulsant effect. Thus, mainly GABA modulatory drugs reveal significant action against flunarizine-induced seizures.

Determination of the role of serotonergic and cholinergic systems in apomorphine--induced aggressiveness in rats.

Aggressive behavior was produced in rats by administration of apomorphine (APO) 20 mg/kg ip. Serotonin (5-HT) agonists, L-tryptophan or 5-hydroxytryptophan and a MAO inhibitor, pargyline, suppressed the APO-induced aggressiveness. However, cyproheptadine was the only one of four 5-HT antagonists used which potentiated the aggressive behavior. Cyproheptadine, metergoline and PCPA released aggressiveness in rats pretreated with a subthreshold dose of APO. Cholinomimetics (pilocarpine, oxytremorine and physostigmine) completely blocked APO induced aggressiveness while cholinolytics (atropine and scopolamine) partially suppressed the inhibiting effect of pilocarpine on aggressive behavior. The results obtained suggest the existence of an interaction between serotonergic, cholinergic systems and dopaminergic system in apomorphine-induced aggressiveness in rats.

Beta-adrenoreceptor antagonists enhance the benzodiazepine-induced suppression of footshock induced fighting in mice.

Aggressive behavior in the footshock induced fighting test (FIFT) was studied after treatment with benzodiazepines (diazepam, nitrazepam, temazepam, medazepam) given alone or in combination with beta-adrenoreceptor antagonists (propranolol, oxprenolol, practolol). With the combinations of those drugs it was found that diazepam (0.5 mg/kg) with propranolol, oxprenolol, and practolol (20 mg/kg); nitrazepam (0.25 mg/kg) with propranolol (10 mg/kg) and nitrazepam (0.1 mg/kg) with practolol (20 mg/kg); temazepam (0.5 mg/kg) with propranolol (10 mg/kg) and temazepam (1 mg/kg) with oxprenolol and practolol (20 mg/kg); medazepam (1.5 mg/kg) with propranolol (10.mg/kg) and medazepam (1 mg/kg) with practolol (20 mg/kg) produced a statistically significant decrease in frequency of fighting episodes in mice as compared with benzodiazepines alone and with control animals. The results demonstrate that beta-adrenoreceptor antagonists potentiate the antiaggressive action of benzodiazepines when given in doses which by themselves do not suppress aggression.

The importance of central nicotinic receptors in footshock-induced aggression in mice.

The action of nicotine and other agonists of central cholinergic receptors on aggressiveness was tested in the footshock-induced fighting test in mice. Nicotine in doses 0.25-2 mg/kg ip and 5-30 micrograms ivtr potentiated the aggressiveness, but a dose of 4 mg/kg ip suppressed it in naive (not pretested) mice. Of other cholinergic agonists betanechol, a specific muscarinic agonist, facilitated the aggression. Similar effect was produced by arecoline, a muscarinic-nicotinic agonist, while carbachol, a compound of pharmacological profile similar to that of arecoline, was ineffective. Mecamylamine, a central nicotinic antagonist, in doses 2 and 4 mg/kg moderately facilitated the aggressiveness, while in a dose of 8 mg/kg inhibited it. Hexamethonium, a peripheral nicotinic antagonist, strongly potentiated aggressiveness. Mecamylamine and hexamethonium antagonized the facilitatory action of nicotine on aggression in non-pretested mice, and of arecoline both in non-pretested an pretested mice, but did not change the effect of betanechol. The results indicate that in addition to muscarinic receptors, the nicotinic receptors in the central nervous system may participate in evoking affective aggression in mice subjected to electric foot-shock.

Xylazine impairs the anticonvulsant activity of conventional antiepileptic drugs in mice.

In this study the influence of xylazine upon the threshold of electrically-induced convulsions and the anticonvulsant action of diazepam, phenobarbital and phenytoin was studied in mice. All drugs were given as solutions intraperitoneally (i.p.). Xylazine did not alter seizure threshold at any of the doses tested (range 0-6 mg/kg i.p.). However, when combined with seizure-increasing doses of phenobarbital and phenytoin, xylazine at a dose of 2 mg/kg significantly (P < 0.05) reduced the ability of these anticonvulsants to increase seizure threshold. Xylazine also reduced the anticonvulsant effect of diazepam, though insignificantly. Our data indicate that xylazine should be contraindicated in animals on the anticonvulsant medication.

The significance of central nicotine receptors in the aggression of isolated mice.

The effect of nicotine, and some nicotinic antagonists on aggressive behavior of isolated mice was tested. Nicotine in doses of 0.5-2 mg/kg ip and 0.005-0.06 mg/mouse ivtr potentiated the aggressiveness. However, higher doses nicotine (4 mg/kg ip and 0.09 mg/kg (Polfa). Co-suppressed the aggression. Mecamylamine, a central nicotinic antagonist in a dose of 2 mg/kg facilitated the aggression while in doses of 4 and 8 mg/kg inhibited it. Hexamethonium, a peripheral nicotinic antagonist, partially suppressed the aggressive behavior. Our results indicate that central nicotinic receptors have also a certain role in mediating the investigated type of mouse aggression.

The cholinergic influences on aggression in isolated mice.

The influence of cholinomimetics and cholinolytics on the isolation-induced aggression in mice was examined. Arecoline, bethanechol, carbachol, oxotremorine, pilocarpine, and physostigmine were found to potentiate aggression, while cholinolytics - atropine and scopolamine - suppressed aggressive behavior. Cholinolytics with no central action did not inhibit aggression. The results indicate that in addition to catecholamines also the cholinergic system may participate in the behavioral model under examination.

The role of the cholinergic system in footshock-induced mouse aggression.

The influence of cholinomimetics and cholinolytics on the aggressive behavior of mice was examined in the footshock-induced fighting (FSIF) test. Pilocarpine, arecoline, physostigmine, oxotremorine and choline chloride were found to potentiate aggression, while anticholinergics - scopolamine, atropine, benactyzine - suppressed aggressive behavior. Studies on the interaction between catecholaminomimetics and cholinergic drugs in the FSIF test suggest that the catecholaminergic and cholinergic systems interact in steering mouse aggression in the behavioral model under examination.

Pharmacokinetic analysis of the level of sulfonamide-trimethoprim combination in calves.

Pharmacokinetic parameters which describe biological availability (AUC, Cmax, tmax) and elimination (kel, t 1/2) of sulfonamides and trimethoprim were determined in calves. Pharmacokinetic analysis was based upon "one compartment model". The average +/- SD half-life in plasma was for sulfametoxazole 12.8 +/- 0.32 h, for sulfamerazine 17.0 +/- 0.75 h and for sulfachloropyridazine 13.1 +/- 0.86 h. The average half-life of trimethoprim in plasma was 11.3 +/- 0.56 h. In fasted calves the concentrations of sulfachloropyridazine and trimethoprim in plasma were higher as compared with fed group.

Intravenous injection of flunarizine elicits epileptiform convulsions. Preliminary evaluation of anti-epileptic drugs.

The possibility to elicit convulsions in rabbits after flunarizine, iv was investigated. A flunarizine solution, 3.3 mg/ml, was given iv at a rate of 1.5 ml/min in three fractional doses every 30 min. Action of anti-epileptic drugs in seizures induced by flunarizine was additionally examined. Convulsive seizures occurred 2-10 min after the last successive dose of flunarizine as alternating clonic and tonic seizures. A treatment with anti-epileptic drugs showed that both phenobarbital at doses 6, 7 and 7.5 mg/kg iv and pentobarbital at doses of 15, 20 and 25 mg/kg, iv did not entirely suppress convulsive seizures, although convulsive episodes were rare. Diazepam at doses of 1-1.5 mg/kg, iv suppressed convulsive seizures.

Convulsive action of flunarizine in rabbits.

High doses of an anticonvulsant agent, flunarizine, given singly or repeatedly produce convulsions in rabbits. Albino rabbits were more vulnerable than mongrel ones. The flunarizine-induced convulsions are interrupted by diazepam.

Influence of chronic aminophylline on the anticonvulsant efficacy of phenobarbital and valproate in mice.

The protective efficacy of phenobarbital (PB, 120 min before testing) and valproate (VPA, 30 min before testing) alone or combined with aminophylline (a single dose of 50 mg/kg, 3-day or 14-day administration twice daily 50 mg/kg at 8.00 a.m. and 8.00 p.m.) was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were given intraperitoneally (i.p.), and the protection provided by PB and VPA was evaluated as the respective ED50 value (in mg/kg). Aminophylline in a single dose of 50 mg/kg (30 min before electroconvulsions) distinctly reduced the protective efficacy of both PB and VPA, reflected by the increase in the respective ED50 values from 22 to 31 mg/kg (p < 0.001) for PB and from 247 to 281 mg/kg (p < 0.001) for VPA. After administration of aminophylline for 3 days (electroshock was performed 30 min after the last aminophylline injection), the respective ED50 values for PB and VPA were 29.5 (p < 0.01) and 269 mg/kg (p < 0.01 vs. saline-treated animals). Chronic treatment with aminophylline (14 days) resulted in further impairment of the protective activity of PB and VPA. Specifically, the ED50 value of PB was 39 mg/kg (p < 0.05 vs. PB+single injection of aminophylline) and that of VPA was 318 mg/kg (p < 0.01 vs VPA+single injection of aminophylline). Plasma levels of both PB and VPA were not affected by chronic aminophylline; moreover, the plasma level of theophylline was even lower after chronic aminophylline as compared with single aminophylline administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial resistance to quinolone antibiotics in Poland.

The resistance of 167 pathogenic bacteria of animal origin to quinolones was determined by the disc diffusion method, and by the minimum inhibitory concentration (MIC) test. The highest resistance of Escherichia coli was found to be against nalidixic acid (NA), 49.1% and flumequine (FLU), 38.2%. The sensitivity of the strains were: ciprofloxacin (CIP; 81.8%); enrofloxacin (ENR; 81.8%); norfloxacin (NOR; 80.0%); and pefloxacin (PE; 76.4%). Salmonella spp. showed 100% sensitivity to CIP, ENR, NOR and PE. A high resistance percentage in the cases of: FLU (86.7%); PE (50.0%); and CIP (26.65%) distinguished the Streptococcus spp. The highest percentage sensitivity of Staphylococci was found with three fluoroquinolones: CIP, ENR and NOR, 94.3% each (66 strains). The studies did not indicate that a total cross-resistance might occur between the examined quinolones.