[Clinical efficacy of cefixime (results of multicenter trials)]. / Klinicheskaia éffektivnost' tsefiksima (rezultaty mul'titsentrovykh ispytanii.

Multicentre trials of cefixime (Cefspan, Fujisawa Pharmaceutical Co., Ltd., Japan) were performed in 1992. The trials involved 137 children and 269 adult patients with inflammatory infections of the respiratory organs and urinary tracts and otorhinolaryngologic affections. Positive clinical and bacteriological results of the trials were stated in 76-90 per cent of the cases. The adverse reactions such as skin eruption and dyspepsia were rare and did not require the specific treatment.

[The results of the therapeutic monitoring of piracetam in parturients and newborn infants]. / Rezul'taty terapevticheskogo monitoringa piratsetama u rozhenits i novorozhdennykh detei.

Overall 30 women in childbirth with preeclampsia and fetoplacental dysfunction received piracetam solution which was given initially in a dose of 5 g by intravenous drip, rapidly since the onset of labour and then every 2 hours till the end of labour in a dose of 2 g by jet injection. This made it possible to increase fetus resistance to hypoxic conditions. The concentrations of piracetam within the range of 60-80 g/l in the blood of women in childbirth should be viewed as minimum therapeutic. A single daily intramuscular injection of piracetam (50 mg/kg) into neonates with encephalopathies may build up blood concentrations equal to 25-60 mg/l after 2 hours. The drug is not detectable in the blood by the moment the next injection is given.

[Study of circadian rhythm of bronchial patency for timely correction and evaluation of the effectiveness of inhalation powder forms of salbutamol in children with bronchial asthma]. / Issledovanie tsirkadial'nogo ritma prokhodimosti bronkhov dlia khrono- korrektsii i otsenki éffektivnosti poroshkovoi ingaliatsionnoi formy sal'butamola u detei, bol'nykh bronkhial'noi astmoi.

A study was made of the circadian rhythms of bronchial patency for ++timely correction and dynamic estimation of the efficacy of powdered inhalation salbutamol (ventodisc) in 30 children aged 7-15 years suffering from persistent recurrent bronchial asthma. The treatment with ventodisc was carried out after basic therapy (euphylline or theopec and/or becotid). During 1 week the children inhaled the drug only at the moments of attacks of obstructed respiration. Starting from the 2nd week of the study ventodisc was applied prophylactically bearing in mind the rhythm of the bronchial tone in hours of minimal values of the maximal volumetric rate of expiration (MVRexp). It has been revealed that an optimal approach to ventodisc administration consists in a preventive drug intake arresting asphyxia attacks, inasmuch children with low values of external respiratory function (particularly in cases where MVRexp is less than 50% of normal) during bronchial asthma attacks are not capable of activating the spraying device and taking the whole drug dose. The use of ventodisc in the chronocorrection mode ameliorated the circadian rhythm of the bronchial tone and minimized the drug requirement 2.3-fold.

[Therapeutic and pharmacological monitoring of individual monotherapy of epilepsy with hexamidine]. / Terapevticheskii i farmakologicheskii monitoring pri individualizatsii monoterapii geksamidinom bol'nykh épilepsiei.

The treatment with primidone alone of 53 epileptic patients with generalized tonic-clonic seizures, partial attacks with elementary symptomatology, and partial fits with complex symptomatology removed them completely in 75, 64.2, and 36.9% of the patients, respectively. The number of attacks was decreased as a result by 50% and over in 90, 78.6, and 73.7% of the patients, respectively. The attainment of such high efficacy of the monotherapy (called by the author intensive in contrast to routine or inadequate therapy carried out, as a rule, in standard doses) appeared possible only under the conditions of individualization of the drug doses which ranged within 250-2500 mg/day. The concentration of phenobarbital, the main end metabolite of primidone, in the blood serum of patients, in whom the attacks were completely arrested and who developed no clinical side effects with no toxic action on the internal organs, ranged from 14 to 59.1 mg/l. In partial fits with complex symptomatology, primidone appeared least effective for those types of fits in the treatment of which it was viewed as most adequate.

[The clinical pharmacology of antiepileptic agents]. / Klinicheskaia farmakologiia protivoépilepticheskikh sredstv.

The correct choice of an antiepileptic drug, its individual dosage and schedule of administration at the beginning of treatment and then during the maintenance therapy promotes a complete control of seizures using one anticonvulsant in 60-90% of patients. The treatment should be initiated with administration of one drug which is adequate for the given type of seizures taking into consideration that different drugs can appear effective in different patients with the same form of epilepsy. One has to choose drugs by consecutively gradually changing them. The optimization of epilepsy treatment should be performed on the basis of the knowledge of the clinicopharmacological characteristic of the main antiepileptic drugs described in the lecture.

[The use of phenobarbital and carbamazepine (finlepsin) in children with epilepsy and cerebral spastic palsy with epileptic syndrome]. / Osobennosti primeneniia fenobarbitala i karbamazepina (finlepsina) u detei bol'nykh épilepsiei i tserebral'nymi spasticheskimi paralichami s épilepticheskim sindromom.

Based on examining 20 patients with infantile cerebral paralyses (ICP) and 18 epileptic patients aged 6 to 14 years it has been demonstrated that the effective doses of carbamazepine do not differ (14-27 mg/kg/day) in both the groups, whereas the effective doses of phenobarbital are higher (5.3 mg/kg/day) in ICP patients than in those suffering from epilepsy (3.65 mg/kg/day; P less than 0.05). In this case the blood concentration of both carbamazepine and phenobarbital was lower in ICP patients (5.1 and 23.1 mg/l, respectively, than in epileptic patients (8.2 and 28.8 mg/l). The drug levels in the blood serum were measured by high-effective liquid chromatography. It was assumed that the efficacy of the lower drug concentrations in ICP patients was related to greater permeability of the blood-brain barrier or with higher sensitivity of "epileptized" neurons in them as compared to epileptic patients. The comparison of the doses and blood concentrations may point to more intense biotransformation of the antiepileptic agents in the body of ICP patients than in patients suffering from epilepsy.

[Allopurinol in the combined therapy of severe forms of epilepsy in children]. / Allopurinol v kompleksnoi terapii tiazhelykh form épilepsii u detei.

Allopurinol was tested as an antiepileptic drug (AED) in children with progressive history of the disease, frequent severe seizures and ineffective conventional AED treatment. A total of 38 children aged 4 months to 10 years were given allopurinol at daily doses of 4 to 5 mg/kg body weight. The drug had positive effects in 10 out of 28 patients having frequent seizures. Complications were not observed. Allopurinol increased serotonin content in platelets. Biochemical investigations proved the therapy with allopurinol alone or combined with other AEDs to be effective.

[Theophylline concentration in the blood of children with persistently recurring bronchial asthma]. / Issledovanie kontsentratsii teofillina v krovi u detei s uporno retsidiviruiushchei bronkhial'noi astmoi.

An antirecurrence effect of theophylline was studied in 32 children aged 3 to 12 years suffering from severe bronchial asthma. The drug dosage was determined by means of a stepwise increase of a daily dose in the range of 10-30 mg/kg/day under control of the patient's general condition and parameters of external respiratory function. Blood theophylline concentration was measured by an immunofluorescent method. The drug individual biotransformation was revealed. Euphylline proved to be a highly effective and safe antirecurrence agent in an individual selection of doses and administration regimens. Combination of theophylline with inhalation beta-adrenomimetics and corticosteroids potentiates its clinical effect without influencing biotransformation.

[Effect of GABA-positive substances on the primary and mirror epileptogenic foci in the hippocampus of rats]. / Vliianie GAMK-pozitivnykh veshchestv na pervichnyi i "zerkal'nyi" épileptogennye ochagi v gippokampe krys.

The effects of beta-alanine, phenibut and muscimol on the activity of the "mirror" (MEF) and primary (PEF) epileptogenic foci were studied in rats on the model of penicillin-induced epilepsy using the direct administration of the drugs into the foci (muscimol only into MEF). All the drugs suppressed the development of electrographic correlates of seizures both in PEF and MEF. The varied characters of the drugs' effects on interseizure epileptiform bursts depending on administration into PEF (provocation) or MEF (no effect) were revealed. Possible dose-dependent mechanisms of the drugs' actions on GABA-A and GABA-B receptors involved in inhibitory control of the activity of epileptogenic foci in the rat hippocamp are discussed.

[Synthesis and analysis of des-Met5-[D-Ala2]enkephalinamide analogs]. / Sintez i izuchenie analogov des-Met5-[D-Ala2]énkefalinamida.

The effects of N- and C-terminal oligoalanine insertions into des-Met5-[D-Ala2]enkephalin amide (I) on the biological activity and spatial structure were examined. The corresponding analogues were obtained by solid-phase synthesis using Sephadex LH-20 ac a polymeric support. Biological activity was assayed via changes in the pain threshold in the rat, body temperature, and also as affinity for opiate receptors. Active analogues were obtained upon modifying the carboxylic group in the tetrapeptide I with di- and tri-D-alanyls. The CD spectra of the C-derivatized analogyes were similar to those of the starting tetrapeptide I and [Met5]enkephalin, whereas the N-derivatized analogues showed essentially different CD spectra.

[Antiepileptic action of met-enkephalin and the rapid development of tolerance to its epileptogenic action]. / Protivoépilepticheskoe deistvie met-énkefalina i bystroe razvitie tolerantnosti k ego epileptiziruiushchemu deistviiu.

It has been shown in chronic experiments on rabbits with electrochemoelectrodes implanted into the dorsal hippocamp that the first administration of met-enkephalin in a dose of 60 to the hippocamp induced the development of an epileptogenic focus (EF) or potentiated the action of the penicillin-induced EF. The second administration of met-enkephalin in the same dose to the hippocamp (interval in a standard scheme of experiments 5 days) did not lead to the production of the EF, which attests to rapid development of tolerance to the epileptizing action of the peptide, with this tolerance being preserved for 20 subsequent days of observation over the animals. After tolerance developed, administration of 60 micrograms met-enkephalin 5 to 10 min before penicillin produced an antiepileptic action, thereby preventing the development of the EF. Met-enkephalin (0.1 and 1 microgram) did not epileptize hippocampal neurons but lowered the action of the penicillin-induced EF after the development of tolerance to the epileptizing action of a large dose of the peptide. The animals did not develop tolerance to the antiepileptic effect of met-enkephalin. The data obtained confirm the hypothesis that different opiate receptors are responsible for the epileptizing (delta-receptors) and antiepileptic (mu-receptors) action of the enkephalin. The effect of small doses of met-enkephalin appears to mirror to a greater degree the involvement of endogenous enkephalins in the epileptogenesis.

[Effect of acupuncture on the activity of experimental epileptogenic foci in the hippocampus of rabbits]. / Vliianie akupunktury na aktivnost' éksperimental'nykh épileptogennykh ochagov v gippokampe krolikov.

Experiments were performed on rabbits with electrochemotrodes implanted into the left and right dorsal hippocamp. The evidence was obtained for the first time as to the marked inhibitory effect of acupuncture on epileptogenic foci created by penicillin microinjections into the hippocamp. The most effective was stimulation of the Min-Men point. The antiepileptic effect was potentiated on combined stimulation of the Min-Men and Yao-Yan-Guan points. The efficacy of the procedure was significantly decreased on stimulation of the points of another acupunctural canal. The epileptiform activity was potentiated by affecting the knowingly inactive points. The antiepileptic effect of acupuncture was significantly reduced with an increase in the number of acupunctures. This might be connected with the development of tolerance to enkephalins by which the effect of acupuncture is most likely mediated.

[Combined effect of a magnetic field and anti-hypoxic agents on epileptogenic foci in the rabbit hippocampus]. / Sochetannoe vliianie magnitnogo polia i antigipoksantov na épileptogennye ochagi v gippokampakh krolikov.

Magnetic field (MF) intensifies the activity of penicillin-induced epileptogenic foci (EF) in the rabbit hippocamp. The same effect was obtained with gutimin. Injections of sodium hydroxybutyrate produced but little changes in hypersynchronous activity as compared to the data of control experiments. Combined influence of MF and gutimin on the rabbits somewhat reduced the quantity of the electrographic correlates of the seizures as compared with the results obtained with MF or gutimin alone. Meanwhile the use of MF coupled with sodium hydroxybutyrate reduced the number of the correlates and the amount of interictal epileptiform discharges as compared with these parameters in experiments where MF alone was applied or in control. It is assumed that MF induces slight hypoxia in the tissues thereby provoking an increase in the epileptogenic foci, whereas sodium hydroxybutyrate but not gutimin compensates for pathological action of MF.

[Decreased acetylcholinesterase activity in the area of epileptogenic foci created by met-enkephalin in the hippocampus of rats]. / Snizhenie aktivnosti atsetilkholinesterazy v oblasti épileptogennykh ochagov, sozdannykh met-énkefalinom v gippokampe krys.

Experiments on rats with electrochemotrodes implanted in the left and right hippocamp have shown that in epileptogenic foci created by microinjections of met-enkephalin or D-ala-2-met-enkephalin into the hippocamp, acetylcholinesterase activity (AChE) was diminished. It is assumed that reduction in AChE activity is an adaptive mechanism by which the excitability of hippocampal inhibitory basket cells, which are sensitive to acetylcholine, is increased.

[Pharmaco-dynamic mechanisms for reducing the activity of an epileptogenic focus with allopurinol]. / Farmako-dinamicheskie mekhanizmy umen'sheniia aktivnosti épileptogennogo ochaga pod vliianiem allopurinola.

Experiments on 73 rats with electrochemotrodes implanted into the dorsal portion of the left hippocamp showed that allopurinol (A) injected intraperitoneally in a dose of 25 and 50 mg/kg decreased the activity of the penicillin-induced epileptogenic foci in the hippocamp and significantly increased the content of serotonin (S) in their area at the 40th minute of the epileptogenesis. Thus, all this provided evidence in favour of a shift in tryptophan metabolism toward an elevated S production that inhibited the development of the epileptic process. A is suggested for clinical use in treating patients with epilepsy, especially in those cases that are resistant to common therapy.