The central action of pizotifen

The central action of the potential antidepressant drug pizotifen (Sandomigran) was studied in mice, rats and rabbits. Pizotifen in doses up to 10 mg/kg i.p. was ineffective in classic tests for antidepressant activity. It neither antagonized the effects of reserpine in rats (hypothermia, ptosis) nor potentiated the effects of amphetamine (in mice and rats), nialamide or L-dopa (in mice) on locomotor activity. However, its antidepressant activity was found in the despair test in rats.On the other hand, pizotifen inhibited the head twitch reaction induced by L-5-hydroxytryptophan in mice (ED₅₀=0.009 mg/kg, i.p.) and by 5-methoxytryptamine (+tranylcypromine) in rats (ED₅₀=0.45 mg/kg, i.p.). It also antagonized tryptamine-induced clonic convulsions of fore-paws in rats (ED₅₀=0.35 mg/kg, i.p.), and in doses of 5–10 mg/kg s.c. inhibited hyperthermia produced by LSD in rabbits. Finally, pizotifen (0.1–0.3 mg/kg, i.v.) inhibited or abolished LSD- or quipazine-induced stimulation of the hind limb flexor reflex of spinal rats; the above effect was not due to noradrenolytic action of the drug. These results suggest that pizotifen strongly blocks the central postsynaptic serotonin receptors.     

Clonidine-induced locomotor hyperactivity in rats

Summary The -adrenergic agonist, clonidine, causes sedation in normal rats. The present study demonstrates that clonidine evokes strong locomotor stimulation in rats pretreated with 6-hydroxydopamine plus reserpine. Similar, but less intensive hyperactivity is observed in rats given clonidine after combined pretreatment with 6-hydroxydopamine plus p-chlorophenylalanine plus -methyl-p-tyrosine, or with reserpine plus low doses of yohimbine. The -adrenolytic drugs, phenoxybenzamine, phentolamine and aceperone, as well as high doses of yohimbine, antagonise the clonidine-induced locomotor stimulation; in contrast, the dopamine receptor blocking agents, pimozide and spiroperidol, exert no antagonistic effect. The results indicate that in the brain of normal animals, clonidine predominantly activates presynaptic -adrenoceptors on noradrenergic neurones and thereby induces sedation. After destruction of the noradrenergic fibres by 6-hydroxydopamine plus reserpine, activation of postsynaptic -adrenoceptors prevails so that hyperactivity results.This study was supported by Polish Academy of Sciences (10.4). Preliminary accounts were presented at the Pharmacology Meeting, Hannover, September 14–17, 1976 and at the 1 st Joint Symposium of Hungarian and Polish Pharmacological Societies, Zakopane, October, 13–15, 1976     

Kniegelenksmeniskusverletzungen im Kindesalter mit Berücksichtigung der Nachuntersuchungen

Zusammenfassung Es wurden 30 Fälle der Kniegelenksmeniskusverletzung im Kindesalter vorgestellt, die operativ behandelt waren. 20 der Behandelten wurden nach 1–12 Jahren nach dem operativen Eingriff nachuntersucht. Es wurden n die Ätiologie, der Verletzungsmechanismus und der klinische Befund besprochen. Die klinische und radiologische Nachuntersuchung ermöglichte die morphologische und funktionelle Auswertung des Kniegelenks nach der Meniskusverletzung.

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Injury of the semilunar cartilages of the knee-joint in childhood

Summary In the paper, 30 patients at the age of 5 till 14 with injuries of the semilunar cartilages of the knee-joint, are presented. All the children were subjected to surgery, and 20 of them underwent same examinations performed in a delay of 1 to 12 years after they had been operated. Both etiology and the injury mechanism subjects are hadled together with the clinical pictures, specific to the age of the young patients. Basing on the clinical and X-ray examinations, the state of the morphological and functional condition of the knee of a child after semilunar cartilage had been removed, was considered and estimated.

     

Control of the RIA method as viewed from the standpoint of the investigation on the kinetics of the insulin-125I-antibody reaction

In this paper attempts were made towards the optimalization and the control of some parameters of the RIA reaction.Basing on the law mass action, as well as on the Scatchard's and Sips's equations, the equilibrium constants for the reversible reaction: insulin-¹²⁵I-antibody for different incubation temperatures were calculated. Moreover a characteristic of the antiinsulin antibody by means of the heterogeneity coefficient was done, as well as the values of the thermodynamic function increments were calculated, which made possible to point out explicitly the optimal shape of the standard curve.     

Effect of therapeutic drug monitoring of amitriptyline and genotyping on efficacy and safety of depression therapy

Modern pharmacotherapy is based on precise adjustment of a dosage schedule to individual requirements of patient. Therapeutic drug monitoring is a method that allows for a more effective treatment approach, especially in the case of a narrow therapeutic index of a drug. Tricyclic antidepressant drugs are characterised by narrow therapeutic index as well as relationship between serum drug concentration and side effects. It was demonstrated that interindividual variability of blood concentrations of tricyclic antidepressant drugs is related to genetic polymorphism of oxidating enzymes participating in metabolism of these drugs. The aim of the study was to estimate the impact of therapeutic drug monitoring of tricyclic antidepressant drugs as well as genotyping on efficacy and safety of endogenous depression therapy. The study included 9 patients with established diagnosis of endogenous depression. Blood serum concentrations of amitryptyline was measured by fluorescence polarisation immune assay (FPIA, Abbott system). Genotype of cytochrome P450 isoenzyme CYP2D6 was determined using PCR-RFLP method. It was demonstrated that monitoring therapy of tricyclic antidepressant drugs in combination with determination of the genotype seems to be more safe and effective. Monitoring therapy and genotyping may be less expensive than the costs of prolonged hospitalisation and risk of side effects.     

Assessment of blood flow velocity during cognitive stimulation in persons with suspected hydrocephalus

The aim of this work is to evaluate middle cerebral arteries (MCA) blood flow velocity changes during performance of linguistic and visuospatial cognitive tasks. Two groups were investigated: eight patients with suspected hydrocephalus without perceptible cognitive disturbances, and eight healthy persons. Blood flow velocity in left and right MCA was recorded with transcranial Doppler sonography while the examined patients were performing three different tasks. The analysis of the results showed differences between the groups concerning both increase of blood flow velocity values and performance patterns. Compared to healthy individuals less increase in blood flow velocity during performance of all tasks and no difference in haemodynamic changes between both hemispheres during task performance were observed in patients with hydrocephalus. The results obtained suggest, that the pattern of functional lateralization in brain in patients with suspected hydrocephalus is probably changed.     

Posttraumatic ectopic calcification as an additional pathologic factor of brachial plexus palsy

The authors describe a case of a 54-year-old male, who was attacked with a broken bottle and wounded in left supraclavicular region. No neurologic deficit was observed immediately after injury. Some days later signs of upper trunk brachial plexus palsy were detected. Gradually symptoms of the Erb syndrome have developed. He was operated on 5 months after injury. During surgery no discontinuity of the brachial plexus was found. Unexpectedly there were an inner scar and free bony fragment compressing the upper trunk and the suprascapular nerve. Both the scar and bony fragment were carefully dissected and removed. Result of surgery: pain relief, restoration of normal sensation and partial restoration of biceps function.     

Stimulating amino acids in epilepsy: possibilities of treatment

Stimulating amino acids (glutamine and aspargine) play an essential role in epileptogenesis. Activating receptors NMDA, AMPA, kainate and metabotropic influence a conduction of ion canals and a beginning, duration and extinction of epileptic discharges. Some of the new anti-epileptic drugs introduced in the recent years modify functioning of glutamine receptors subtypes. It is expected that they can also decrease a release of glutamines, amplify a GABA-ergic suppression and block sodium channels. Most information about these drugs in epileptogenesis was received in animal experiment which is an excuse for a lack of certainty in a parallel referring their mechanisms to the central nervous system in a man. Treatment resistant focal or general epilepsies and some epileptic syndromes are the most often appearing indications for using agents producing an effect on activating amino acids system. They are most often used in an added therapy, more rarely in a monotherapy. Some negative comments concern not very clear influence on cognitive functions, however some hope arises due to a potential neuroprotective mechanism being a result of a decreased glutamine release. The drugs blocking a stimulating transmission should be a good supplement for a present possibilities of epileptic treatment.     

Is there an effective neuroprotective treatment of Parkinson's disease? (therapeutic possibilities against the background of etiopathogenetic concepts

The author presents current views on neuroprotective strategies in therapy of idiopathic Parkinson's disease. They are the result of different aetiopathogenetic concepts of Parkinson's disease. The concepts of loss of nigral cells as a result of aging, apoptosis or genetic defect (alpha-synucleine) are not sufficiently proven and their role is only hypothetic. Therapeutic use of nerve growth factors seems to be a promising novel strategy but there are technical problems how to deliver them to the brain. One of the most and widely acceptable concept is the theory of the role of oxidative stress in pathogenesis of Parkinson's disease. It was a scientific basis for clinical trials with selegiline (DATATOP, SINDEPAR, PDRG) which results were unfortunately disappointing, mostly because of symptomatic effect of selegiline. Another interesting concept seems to be the excitotoxicity of amino acids (like glutamate) and amantadine is the well known drug with recently discovered antagonism to NMDA receptors. In only one retrospective clinical trial in humans its neuroprotective effect was proven, but we need now well prepared prospective trials with this drug to confirm this result. So far, despite the hopes concerning selegiline no one effective neuroprotective agent is available in treatment of Parkinson's disease.