Skeletal Deformity in Children with Primary Hyperparathyroidism.

Skeletal deformation like genu valgum is reported to be rare in Primary hyperparathyroidism (PHPT). The solitary adenoma or hyperplasia of the parathyroid glands are the cause in 80-85% of the cases. We report 2 cases of girls on 12 years and 15 years of age, complaining from pain and genu valgum deformation of the lower extremities before the planned orthopaedic surgical correction. The first patient had complaints for 3 years and lost ability to walk independently, the second case lost normal gate for a period of 5 months. The paraclinical screening discovered hypercalcemia, hypophosphatemia, elevated alkaline phosphatase, normal creatinine, raised parathormone. In the first case the X-rays depicted fibrocystic osteodistrophy from a hyperparathyroid type with bone cysts, giant cell "brown tumors" and pathological bone reorganization, in the second case - coarse fibrous structure of the left knee joint with genu valgum with bone cysts in the distal metaphysis of the left femur. The ultrasound of the thyroid gland found oval hypoechoic formations with suspicious origin from the parathyroid glands. These findings were confirmed from the SPECT/CT pointing active adenomas in the parathyroid glands. Skeletal deformation like genu valgum is the reason to search for the primary diagnosis in our 2 cases. Investigation of the serum calcium and parathormone are diagnostic in 100%. The imaging diagnosis has a critical role for indicating surgical treatment of the parathyroid gland adenoma. Key words: genu valgum, hypercalcemia, paediatric parathyroid adenoma, ultrasound, SPECT/CT.

An ethological analysis of close-contact inter-cat interactions determining if cats are playing, fighting, or something in between.

Intraspecific social interactions in domestic cats are often categorised as affiliative or agonistic. However, public or professional assessment of encounters can have difficulty distinguishing rough-and-tumble play from true agonism. One possible issue is the potential occurrence of elements of both, play and agonism, within inter-cat play, for example when one cat wants to terminate a bout of play but the other seeks to continue the interaction, which subsequently may provoke more overt agonistic behaviour. To test this hypothesis, we conducted behavioural observations of 105 unique dyadic interactions of domestic cats (N = 210) captured on videos collected from owners and YouTube. We assessed cats for the frequency and duration of six behavioural elements. The dataset was reduced using PCA with a varimax rotation and factor scores were used to classify the population using hierarchical cluster analysis. To validate the identified clusters, the average scores of the constituent factors were compared and the data on interactions were labelled by four cat behaviour experts as "playful", "intermediate" or "agonistic". In addition, to evaluate properties of expert-labelled categories we used linear discriminant analysis followed by an ordinal regression. The results showed considerable convergent validity in factor distributions between clusters and expert-labelled groups: reciprocal wrestling was most closely associated with a group of playfully interacting cats, while vocalisation and chasing were associated with the agonistic group. The intermediate group, while having characteristics of both, was more closely related to the playful group than the agonistic group, with prolonged exchanges of interactive behaviours being a predominant feature. Thus, our findings support the suggestion of there being an intermediate category between mutual social play and agonism. This might escalate into a fully agonistic encounter, but does not necessarily reflect a break down in their social relationship but rather a short-term disagreement in social priorities.

Foamability of aqueous solutions: Role of surfactant type and concentration.

In this paper we study the main surface characteristics which control the foamability of solutions of various surfactants. Systematic series of experiments with anionic, cationic and nonionic surfactants with different head groups and chain lengths are performed in a wide concentration range, from 0.001 mM to 100 mM. The electrolyte (NaCl) concentration is also varied from 0 up to 100 mM. For all surfactants studied, three regions in the dependence of the foamability, VA, on the logarithm of surfactant concentration, lgCS, are observed. In Region 1, VA is very low and depends weakly on CS. In Region 2, VA increases steeply with CS. In Region 3, VA reaches a plateau. To analyse these results, the dynamic and equilibrium surface tensions of the foamed solutions are measured. A key new element in our interpretation of the foaming data is that we use the surface tension measurements to determine the dependence of the main surface properties (surfactant adsorption, surface coverage and surface elasticity) on the surface age of the bubbles. In this way we interpret the results from the foaming tests by considering the properties of the dynamic adsorption layers, formed during foaming. The performed analysis reveals a large qualitative difference between the nonionic and ionic surfactants with respect to their foaming profiles. The data for the nonionic and ionic surfactants merge around two master curves when plotted as a function of the surface coverage, the surface mobility factor, or the Gibbs elasticity of the dynamic adsorption layers. This difference between the ionic and nonionic surfactants is explained with the important contribution of the electrostatic repulsion between the foam film surfaces for the ionic surfactants which stabilizes the dynamic foam films even at moderate surface coverage and at relatively high ionic strength (up to 100 mM). In contrast, the films formed from solutions of nonionic surfactants are stabilized via steric repulsion which becomes sufficiently high to prevent bubble coalescence only at rather high surface coverage (> 90%) which corresponds to related high Gibbs elasticity (> 150 mN/m) and low surface mobility of the dynamic adsorption layers. Mechanistic explanations of all observed trends are provided and some important similarities and differences with the process of emulsification are outlined.

Effects of MPEP on avoidance learning in rats.

In recent years metabotropic glutamate receptors (mGluRs) have received considerable attention as a potential target for psychotropic drugs, but their influence on learning and memory is still unclear. The aim of the present study was to examine whether intraperitoneal (i.p.) administration of selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyrydine (MPEP), injected prior to, immediately after or 30 min after training, affects acquisition and/or retrieval of the inhibitory step-down and active shuttle-box avoidance in rats. Our results indicate that 5 or 10 mg/kg i.p. MPEP in all tested groups impaired memory consolidation of step-down training without affecting acquisition and had no effect on learning and retention in shuttle-box trained rats. The data are in agreement with the statement that mGluR5s may contribute very little and task-dependently to the actual acquisition of new information, but memory formation, appears to require mGluR5s through modulation of consolidation and/or recall.

Effects of beta-adrenoceptor blocker pindolol, calcium antagonist verapamil and their combination on retention in step-down- and shuttle-box-trained rats and on brain biogenic monoamines.

The effects of the beta-adrenoceptor blocker pindolol and the calcium antagonist verapamil administered alone or in combination on retention in step-down- and shuttle-box-trained rats and on the biogenic monoamine levels in the frontal cortex and hippocampus were examined. The chronic oral treatment with pindolol impaired retention in step-down- and shuttle-box-trained rats, decreasing the dopamine (DA) and noradrenaline (NA) levels and increasing the serotonin (5-HT) levels in the cortex and hippocampus. Verapamil did not influence retention in step-down- and shuttle-box avoidance situation and the biogenic monoamine levels in the frontal cortex and hippocampus. It should, however, be noted that the chronic oral treatment with verapamil completely abolished the retention-impairing effect of pindolol, restoring to normal DA, NA and 5-HT levels. These findings might be of interest to clinical practice and suggest the necessity for using a combination of beta-blockers with Ca2+ antagonists in case of prolonged treatment of cardiovascular diseases.

Effect of the calcium channel blockers nifedipine and diltiazem on pentylenetetrazole kindling-provoked amnesia in rats.

A large body of research supports the view that memory disturbance is an integral part of epilepsy. Deficit in various behaviour tasks has been found in rats subjected to experimental epilepsy-pentylenetetrazole (PTZ) kindling. In the present study we examined the effect of post-training administered calcium channel blockers nifedipine (10 and 40 mg/kg) and diltiazem (10 and 30 mg/kg) on amnesia induced by PTZ kindling in shuttle-box- and step-down-trained rats. Retention in nifedipine- or diltiazem-treated kindled animals was significantly improved compared to the kindled controls. The mechanisms of action of calcium antagonists studied is considered. Taken together with the data about calcium channel blocker anticonvulsive activity, the results of this study further suggest that nifedipine and diltiazem might be useful in the treatment of cognitive disorders in epileptic patients.

The GABA-B antagonist CGP 36742 prevent PTZ-kindling-provoked amnesia in rats.

Deficit in active and inhibitory avoidance behaviour has been found in pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the GABA B antagonist CGP 36742 on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in CGP 36742-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of CGP 36742 is considered. The favourable effect of the GABA B antagonist in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice.

Effects of flunarizine and nitrendipine on electroconvulsive shock- and clonidine-induced amnesia.

This study was designed to examine the calcium channel blockers flunarizine and nitrendipine for their ability to prevent electroconvulsive shock (ECS)- or clonidine-induced deterioration of the inhibitory avoidance performance (step-down) in rats. Flunarizine (10 mg/kg) and nitrendipine (40 mg/kg) were found to prevent the ECS- or clonidine-provoked amnesia after oral administration for 12 days. The mechanisms of action of the two drugs are considered. The results of this study further suggest that calcium antagonists might be useful in the treatment of cognitive disorders.

Adaptive changes in the effects of angiotensin II on the convulsive-seizure threshold in cases of altered sensitivity of dopamine receptors.

The adaptive changes in the effects of the neuropeptide angiotensin II (AT II) on the convulsive-seizure threshold were studied. AT II was injected intracerebroventricularly (i.c.v.) at a dose of 1 micrograms/mouse and convulsive seizures were induced by timed intravenous infusion of pentylenetetrazol (PTZ) in male albino mice. The sensitivity of DA receptors was altered by: repeated (14 days) intraperitoneal (i.p.) injection of the DA receptor antagonist pimozide (1 mg.kg-1) and subsequent withdrawal of the antagonist for 7 or 21 days; and repeated (14 days) subcutaneous (s.c.) injection of the DA receptor agonist apomorphine (0.5 mg.kg-1). The convulsive-seizure-increasing effect of AT II was enhanced after multiple administration of pimozide and particularly after its withdrawal for 21 days. This effect was also enhanced though to a lesser degree by repeated treatment with apomorphine. Apomorphine applied 21 days after withdrawal of pimozide decreased the pimozide-enhanced effect of AT II. All these adaptive changes in the effects of AT II on the PTZ convulsive-seizure threshold might be associated with the altered receptor-receptor (AT II-DA-GABA) interactions in the brain structures participating in the regulation of the convulsive-seizure threshold.

Effect of dotarizine on electroconvulsive shock or pentylenetetrazol-induced amnesia and on seizure reactivity in rats.

Dotarizine (DOT), a compound performing both as calcium antagonist and as 5-HT2 receptor antagonist, was evaluated for its ability to protect against electroconvulsive shock (ECS)- and pentylenetetrazol (PTZ)-induced performance deficit in a passive avoidance "step-down" task in rats. Its effect on electric and PTZ seizure models was also studied. DOT administered orally at a dose of 50 mg/kg for 5 days before learning had no significant effect on retention tests given 3 h, 24 h and 7 days after the training session. It should be noted, however, that DOT completely prevented ECS- and PTZ-induced amnesia in passive avoidance situation. DOT had a pronounced protective effect against electric seizures but did not affect PTZ seizures. The present results provide additional evidence for the role of serotonergic neurotransmitter system and calcium homeostasis for memory and seizure reactivity and may be important in the development of effective treatment strategies for memory dysfunction.

Effects of the calcium antagonists verapamil and nitrendipine on carbamazepine withdrawal.

This study was aimed at examining the effects of two frequently used Ca2+ antagonists, nitrendipine and verapamil, on withdrawal after cessation of long-term treatment with the anticonvulsant drug carbamazepine in rats. The 48-h interruption of long-term (21 days) carbamazepine treatment led to the appearance of withdrawal characterized by increases in seizure intensity, the percentage of rats with tonic seizures and mortality. Oral treatment with the two calcium antagonists in combination with carbamazepine abolished the signs of carbamazepine withdrawal. Seizure intensity, the percentage of rats with tonic seizures and mortality in the groups treated with the combinations of carbamazepine + verapamil and carbamazepine + nitrendipine were significantly lower than those of the group of rats treated with carbamazepine alone. In conclusion, some Ca2+ antagonists could attenuate the manifestations of anticonvulsant withdrawal and thus could be used as adjuvants in long-term anticonvulsant therapy.

Effects of verapamil on electroconvulsive shock- and clonidine-induced amnesia.

The effect of the Ca2+ blocker verapamil on amnesia induced by electroconvulsive shock (ECS) or by the alpha-adrenoceptor agonist clonidine was studied in male Wistar rats trained in passive avoidance task ("step down"). Clonidine (0.1 mg/kg, i.p.) and ECS induced a pronounced amnesia, significantly reducing the percentage of rats that had acquired the task upon retention tests, given 3 h, 24 h and 7 days after training. Verapamil (10 mg/kg) administered orally for 12 days (5 days before and 7 days after training) completely abolished the ECS- or clonidine-induced amnesia. These data suggest that calcium channel blocker verapamil has a protective effect against experimentally provoked memory deficit and might be useful for the treatment of cognitive disorders.

Effect of AT II on the exploratory behaviour of rats. Interactions with elymoclavine and bromocryptine.

The interaction between the octapeptide angiotensin II (AT II) and the DA-ergic agents (agonists)--the ergotic alkaloid elymoclavine and bromocryptine--during exploratory behaviour was studied in experiments on male albino rats. The changes in the horizontal and vertical activity of the exploratory behaviour and the hole-board activity were investigated using an Opto-Varimex apparatus. AT II, elymoclavine and bromocryptine were applied alone. The frequency of rearing and ambulation was increased with all substances applied (the effect being most pronounced on the 10th min), while the hole-board activity decreased. Elymoclavine potentiates the effect of AT II during exploratory behaviour. The effects of the drugs tested on the exploratory behaviour most probably result from the interaction between AT II receptors, dopamine receptors and through GABA-ergic neurotransmission, in the respective brain zones responsible for behaviour.

Behavioral changes as a result of dotarizine or flunarizine influence on dopaminergic neurotransmission in the striatum.

In experiments on rats, we studied the changes in stereotypy induced by apomorphine (2.5 mg/kg i.p.) or amphetamine (2 mg/kg i.p.) and in haloperidol (1 mg/kg i.p.) catalepsy in rats treated with dotarizine (25 mg/kg orally), flunarizine (25 mg/kg) or vehicle for 10 days. Dotarizine did not induce any significant changes in the intensity and duration of apomorphine- or amphetamine-induced stereotypy nor in haloperidol-induced catalepsy. The flunarizine-induced changes in the behavioral effects of apomorphine, amphetamine and haloperidol suggest the decrease of striatal dopaminergic neurotransmission, whereby the risk of occurrence of extrapyramidal side effects of the drug when used in clinical practice. Dotarizine is not associated with such a risk.

Effect of p-chlorophenylalanine on the central nervous excitability threshold and on the activity of some central depressants.

The effect of p-chlorophenylalaine (pCPA)on the central nervous excitability threshold for the neurostimulants pentetrazol, picrotoxin and strychnine inflused intravenously was evaluated in male albino mice. The effect of pCPA pretreatment was also studied in mice treated both with the neurostimulants and with central depressants meta-tolylcarbamide (MTC), phenacemide (phenylacetylurea, Phenurone) or phenobarbitol sodium (PBS). pCPA applied alone or together with MTC, phenacemide and pbs lowered the central nervous excitability threshold for the three central stimulants used in the majority of the experiments.

Comparative effects of centrophenoxine on the picrotoxin convulsive-seizure threshold in non-irradiated and irradiated mice.

A comparative study is made of the effect of centrophenoxine (CP) on the picrotoxin convulsive-seizure threshold (PCST) in non-irradiated and irradiated 3 and 7 days previously male mice. It is found that the CP appliked intracerebroventricularly in doses of 200 and 400 micrograms/mouse (weight 18-22 g), increases PCST. In non-irradiated mice the PCST-increasing effect of CP occurs rapidly (5 min) and it is brief (it can be observed until the 15th min). When the irradiation is performed three days previously, the PCST-increasing effect of CP is prolonged (it is observed until the 6th hour after its application). When the irradiation is performed seven days previously the characteristic features of the PCST-increasing effect of CP are similar to those in the early stage (3 days), the only difference being that the duration of the effect is prolonged to 120 min. Generally, these specificities of the CP effect are valid for all three phases of the convulsive seizure (general excitation, clonic convulsive seizure and tonic convulsive seizure.

Apomorphine stereotypies and transmitter mechanisms in the striatum. II. Interactions between GABA-ergic and cholinergic transmission.

The interactions between the GABA-ergic and cholinergic transmissions in the striatum of male mice are determined through microinjection in the striatum of agents influencing these types of transmission in cases of apomorphine stereotypies. It is found that the agents acting on the cholinergic transmission (agonists and antagonists of the muscarinic and nicotinic cholinoreceptors), antagonize considerably the reducing effect on apomorphine stereotypies of the agents acting on GABA-ergic transmission. Conversely, the agents acting on GABA-ergic transmission (pre- and post-synaptic) intensify or weaken the effects of the agents acting on the cholinergic transmission with respect to apomorphine stereotypies, though the difference is not entirely significant. The influence of the effects of the agents acting on the GABA-ergic transmission in cases of apomorphine stereotypies is thought to be due to the antagonistic action of the striatal cholinergic neurones on the GABA-ergic neurones, while the latter interact with the striatal dopaminergic neurones either directly or through the mediation of substantia nigra. The lack of direct interactions between the GABA-ergic and the cholinergic neurones in the striatum explains the weak influence on cholinergic transmission exerted by the agents acting on the GABA-ergic transmission with respect to apomorphine stereotypies.

Apomorphine stereotypies and transmitter mechanisms in the striatum. I. Changes in the apomorphine stereotypies caused by drugs acting on the GABA-ergic, dopaminergic and cholinergic transmission.

Experiments on male albino mice were carried out in order to determine the effects of drugs connecting with the GABA-ergic, dopaminergic and cholinergic transmission, on apomorphine stereotypies. The agents acting on GABA-ergic transmission are found to reduce the intensity of apomorphine stereotypies in the following order (arranged from strongest to weakest effect and expressed in doses of microgram per mouse: GABA (100), aminooxyacetic acid (5), diazepam (20), picrotoxin (1), GABA (10), semicarbazide (30), picrotoxin (0.1). The agents acting on the dopaminergic transmission also reduce apomorphine stereotypies in the following order: haloperidol (20;2), L-DOPA (500 mg/kg, i. p.), alpha-methylparatyrosine (150 mg/kg, i. p.) diethyldithiocarbamate (200). The strongest antagonistic effect in the two groups of agents studied was found for haloperidol. The agents acting on the cholinergic transmission (agonists and antagonists of muscarinic and nicotinic cholinoreceptors) have no significant effect on apomorphine stereotypies. It is assumed that the striatum is not the only brain structure responsible for apomorphine stereotypies.

Interactions of angiotensin II with piracetam in exploratory behavior and convulsive-seizure threshold.

The interactions between angiotensin II (AT II) and piracetam in exploratory behavior of rats in open field and in pentylenetetrazol (PTZ) convulsive-seizure threshold in mice were studied. AT II at a dose of 0.5 microgram injected intracerebroventricularly (i.c.v.) increased exploratory behavior. Piracetam at a dose of 600 mg.kg-1 administered orally twice daily for 7 days increased the frequency of the exploratory behavior components. AT II decreased this effect of piracetam. AT II (0.5 microgram i.c.v.) tended to increase the PTZ convulsive-seizure threshold. On single administration piracetam had no effect on the convulsive-seizure threshold but on multiple administration it increased the threshold. The two drugs applied together increased the PTZ convulsive-seizure threshold to a larger extent as compared to the effect they exerted when administered alone. The changes in exploratory behavior and in convulsive-seizure threshold, increased by the combination of AT II and piracetam, are explained by the interactions between the two drugs at the level of AT II and GABA binding sites in brain.