[Psychiatric aspects of plant poisonings]. / Pflanzenvergiftungen--psychiatrische Aspekte.

Plant poisonings have been reported since ancient times. Despite this, little attention is paid to intoxications with herbal poisons by psychiatric literature and the danger from poisonous plants is commonly underestimated. This problem is discussed here, and advice for the prevention of plant poisonings and generally dealing with patients intoxicated by herbal poisons is given.

Altered activities of rat brain metabolic enzymes in electroconvulsive shock-induced seizures.

PURPOSE: Electroconvulsive shock (ECS) induces generalized seizure activity and provides an excellent experimental model for studying the effects of global electrical stimulation on various biochemical parameters. The aim of this work was to investigate the influence of a single or repeated ECS-induced seizures on rat brain metabolism. METHODS: Experiments were carried out on female Hannover-Wistar rats divided into four groups: (a) the control group, which was intact; (b) the 1ECS group, which was killed 2 h after single ECS; (c) the 5ECS group with 24 h rest, which was killed 24 h after the fifth daily ECS; and (d) the 10ECS group with 48 h rest, which was given ECS every 48 h and killed 24 h after the tenth ECS. Activities of glutamate dehydrogenase (GLDH), aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK) in the frontal cortex, cerebellum, hippocampus, and pons/medulla regions were determined. RESULTS: Increased AST, ALP, LDH, and CK activities were detected in all examined regions of the 1ECS and 5ECS groups. ALT activity was increased in both these groups, except in the hippocampus of the 5ECS group, where increased GGT activity was detected. In the hippocampus of 1ECS group, GLDH activity was decreased. Increased hippocampal AST and cortical CK activities, together with increased LDH activities in the cortex, cerebellum, and pons/medulla, were found. CONCLUSIONS: ECS treatment induces region-specific changes in metabolic activity. Neither a 24-h nor a 48-h rest period between two ECSs was sufficient for complete brain recovery, although most of the observed increased enzyme activities present in 1ECS and 5ECS were not present in 10ECS.

Altered activities of rat brain metabolic enzymes caused by pentylenetetrazol kindling and pentylenetetrazol--induced seizures.

The aim of our study was to investigate amino acid and energy metabolism of pentylenetetrazol (PTZ)-kindled animals. Glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamyltransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase (CK) were determined in the frontal cortex, cerebellum, hippocampus and pons-medulla regions of Hannover-Wistar rats. The rats were randomly divided into four experimental groups: (a) control; (b) rats which received a single PTZ injection in a subconvulsive dose of 40 mg/kg i.p.; (c) rats which received a single PTZ injection in a convulsive dose of 50 mg/kg i.p.; and (d) PTZ-kindled rats. Kindling increased ALP activity throughout the brain, elevated AST as well as LDH activity in the frontal cortex and hippocampus and decreased CK activity in the frontal cortex and cerebellum. Acute seizures of the same intensity did not induce these alterations. The observed effects therefore are obviously linked to the kindling phenomenon and not to seizure activity. Changes appeared mainly in the frontal cortex and hippocampus, i.e. brain areas believed to be directly involved in kindling.

Electroconvulsive shock in rats: changes in superoxide dismutase and glutathione peroxidase activity.

Seizures trigger a variety of biochemical processes including an influx of extracellular Ca(2+), activation of membrane phospholipases, liberation of free fatty acids, diacylglycerols, eicosanoids, lipid peroxides and free radicals. These lipid metabolites along with abnormal ion homeostasis may be involved in cell injury and cell death. The aim of this study was to determine brain antioxidant enzyme activities in rats with electroconvulsive shock (ECS)-induced seizures. ECS, single or repeated, induced a decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in various brain regions. The most prominent changes of enzymatic activities were observed in rats that received five ECSs with 24-h recovery period between them. Decreased SOD activity was observed in the frontal cortex of all treated animals except those sacrificed 24 h after single ECS, in the cerebellum of the animals that received repeated ECSs, in the hippocampus of animals that were decapitated 2 h after a single ECS and in the pons-medulla region of rats that received five daily ECSs. Decreased GPX activity was found in all examined brain regions of the rats that received five ECSs, the cortex and hippocampus of rats that were decapitated 2 h after single ECS and the cortex of those that received 10 ECSs with 48 h between them. The results show that neither 24-h nor 48-h recovery period was sufficient for the normalisation of antioxidative enzyme activities after repeated ECS treatment.

Lithium plus pilocarpine induced status epilepticus--biochemical changes.

The aim of the study was to investigate the changes in biochemical mechanisms facilitating cellular damages in the lithium plus pilocarpine treatment and the resulting status epilepticus. The whole brain free fatty acid (FFA) level as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamoyl transferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase in the frontal cortex, cerebellum, hippocampus and pons-medulla region of Hannover-Wistar rats were determined. The control group was intact with no previous experimental history. LiCl (125 mg/kg i.p.) was injected 20 h prior to pilocarpine (30 mg/kg i.p.) and the treated rats were sacrificed 1 or 2 1/2 h after pilocarpine administration. The results show that lithium plus pilocarpine administration and the resulting status epilepticus produced the significant increase of the brain FFA content. Decreased GPX activities were detected in the frontal cortex, cerebellum and hippocampus of the treated rats without the accompanying decrease of SOD activity. Increased AST and LDH activities were observed in the frontal cortex, increased soluble ALP activities in the frontal cortex and pons-medulla region whereas the increased activity of membrane bound ALP was detected in the hippocampus of the rats with status epilepticus. Activities of the other analysed enzymes did not change in the examined brain regions. The presented data indicate clear regional differences of biochemical changes caused by lithium plus pilocarpine treatment and the resulting status epilepticus, frontal cortex being the most affected site.

The influence of nimodipine, nicardipine and amlodipine on the brain free fatty acid level in rats with penicillin-induced seizures.

1. The aim of this study was to investigate the effects of the calcium channel blockers, nimodipine, nicardipine and amlodipine, on the brain free fatty acid (FFA) level in rats with chemically-induced seizures. 2. The study was carried out on Hannover-Wistar rats. Animals were anesthetized and placed in a stereotaxic apparatus. Each of them received an injection of penicillin (5000 IU/5 microliters) into the left lateral ventricle (i.c.v.). Various doses (1, 3, 10 or 30 mg/kg) of nimodipine, nicardipine or amlodipine had been injected i.p. 30 min before the penicillin application. The rats were decapitated 5 min after the occurrence of epileptic seizures. FFAs were quantified by gas chromatography using the internal standard method. 3. The results demonstrate that i.c.v. injection of penicillin was associated with significant increase in the brain FFA concentration. Tested doses of nicardipine and amlodipine did not influence the increase of the brain free palmitic, stearic, oleic and arachidonic acid level while nimodipine prevented the accumulation of free palmitic, oleic and arachidonic acid in rats with penicillin-induced seizures. Statistically insignificant decrease of steric acid was observed in animals pretreated with nimodipine. 4. It maybe assumed that the brain FFA accumulation caused by i.c.v. penicillin administration is not predominantly associated with a disturbance in calcium homeostasis via L-type voltage-sensitive calcium channels, but by some other membrane and/or intracellular mechanisms.

Education in clinical pharmacology at the Rijeka School of Medicine, Croatia.

OBJECTIVE: Irrational drug prescribing is a global problem that exists both in developed and developing countries. Education is the key to improved effectiveness and safety in drug therapy. Development of clinical pharmacology (CP) as an independent discipline at the Rijeka School of Medicine has been slow and unsatisfactory. It was taken only as a part of some postgraduate courses. In the 1995/1996 academic year clinical pharmacology was offered for the first time to sixth year medical students as a non-mandatory subject. The purpose of this study was to emphasize the importance of education in clinical pharmacology at the Rijeka School of Medicine. METHODS: This survey was an uncontrolled study based on responses to questionnaires and a test consisting of written patient problems given to sixth year medical students and to general practitioners who were following a course in clinical pharmacology. RESULTS: The results of the questionnaire showed that both undergraduate and postgraduate students consider that they are not being adequately trained to prescribe drugs rationally and that they believe that clinical pharmacology should become a mandatory subject in the undergraduate medical curriculum. The results of the written patient problem test support this. Both groups of students demonstrated greater skills in solving the diagnostic part than the therapeutic part of the test. A great improvement in the students' ability to solve the therapeutic part was observed after they had completed the CP course. CONCLUSION: The results of this survey underline the necessity of education in clinical pharmacology.

The influence of nicardipine and ifenprodil on the brain free arachidonic acid level and behavior in hypoxia-exposed rats.

1. The effects of the calcium channel blockers, nicardipine and ifenprodil, on the brain free arachidonic acid level and learning ability in rats exposed to hypoxia were examined. 2. Adult rats were injected with 0.003; 0.01; 0.03; 0.1; 0.3 or 1.0 mg/kg of tested drugs i.p. Thirty min later the learning ability was tested in a passive avoidance task according to the step-through procedure. Immediately after the training trial, the animals were subjected to a period of oxygen deprivation hypoxia until the loss of the righting reflex. The retention trial was carried out 24 hr later. 3. The other groups of animals were pretreated with mentioned substances before hypoxia-exposure. Fifteen min after the loss of the righting reflex they were decapitated and brains were frozen in liquid nitrogen. The brain free arachidonic acid level was quantified by gas chromatography. 4. Both nicardipine and ifenprodil were effective in preventing a memory decline in hypoxia-exposed rats but did not prevent the accumulation of the brain free arachidonic acid in hypoxia-exposed rats. 5. The protective effects of both substances in behavioral studies during acute brain damage caused by hypoxia could not be explained by the prevention of the increase of the brain free arachidonic acid, but by some other mechanism.

The influence of nimodipine and MK-801 on the brain free arachidonic acid level and the learning ability in hypoxia-exposed rats.

1. The influence of voltage dependent calcium channel blocker (VDCC), nimodipine and N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 on the brain free arachidonic acid (FAA) level and on the learning ability in hypoxia-exposed rats was examined. 2. Some animals were decapitated after cerebral hypoxia had been obtained and the brain FAA level was determined by gas chromatography. The other animals were trained in a passive avoidance procedure and were exposed to hypoxic conditions immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 hours later. 3. Various doses of nimodipine (0.03; 0.1; 0.3 and 1.0 mg/kg) and MK-801 (0.03; 0.1 and 0.3 mg/kg) had been injected 30 minutes before biochemical or behavioral procedures started. 4. It was found that hypoxia strongly increased the brain FAA level and impaired the retention of the passive avoidance response. 5. Pretreatment with 0.3 mg/kg and 1.0 mg/kg of nimodipine prevented the brain FAA accumulation. It has also been shown that all tested doses of nimodipine significantly improved the retention deficit in the animals exposed to hypoxia. 6. Neither the one of tested doses of MK-801 influenced significantly the increase of the brain FAA level and/or passive avoidance behavior in hypoxic animals. 7. These results confirm the hypothesis that the brain FAA accumulation and cognitive impairment, caused by hypoxia, are maybe associated with disturbances in calcium homeostasis and that nimodipine may be useful in ameliorating the hypoxia-induced brain tissue damage. Blocade of NMDA receptor-channel complex by MK-801 was not sufficient to prevent hypoxia-induced neuronal damage.

Effects of nimodipine, felodipine and amlodipine on electroconvulsive shock-induced amnesia in the rat.

The effects of various doses (0.03, 0.1, 0.3 or 1.0 mg/kg) of the Ca2+ channel blockers nimodipine, felodipine and amlodipine on the learning ability of rats exposed to electroconvulsive shock were examined. The animals were trained in a passive avoidance procedure. The drugs tested were injected 30 min before the learning trial started. The electroconvulsive shock was given immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 h later. It was found that electroconvulsive shock strongly impaired the retention of the passive avoidance response. Nimodipine, felodipine and amlodipine did not influence the passive avoidance behavior in the sham electroconvulsive shock group, but significantly improved the retention deficits in the animals exposed to electroconvulsive shock. These findings support the hypothesis that perturbations in Ca2+ homeostasis can contribute to the memory deficits associated with electroconvulsive shock. The antiamnestic effects of the substances tested make them interesting candidates for clinical trials in patients with cognitive impairment caused by electroconvulsive shock therapy.

Effects of nicardipine, felodipine and nifedipine on passive avoidance behavior of intact and hypoxia-exposed rats.

The effects of various doses (0.03, 0.1, 0.3 or 1 mg/kg) of the calcium channel blockers nicardipine, felodipine and nifedipine on the learning ability in intact rats and on hypoxia-induced retention deficits were examined. All animals were trained in a passive avoidance procedure. The drugs tested had been injected 30 minutes before the learning trial started. Some animals were exposed to a hypoxic condition immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 hours later. It was found that hypoxia strongly impaired the retention of the passive avoidance response. Nicardipine, felodipine and nifedipine did not influence the passive avoidance behavior in the intact animals, but significantly improved the retention deficits in the animals exposed to hypoxia. The effects of the substances tested were dose-dependent. These findings support the hypothesis that perturbations in calcium homeostasis can contribute to the memory deficits associated with hypoxic conditions.

Lesions of the nucleus basalis magnocellularis in immature rats: short- and long-term biochemical and behavioral changes.

Short- and long-term effects of unilateral lesions of the nucleus basalis magnocellularis (NBM) on cortical choline acetyltransferase (ChAT) activity and passive avoidance conditioned responses were examined in immature rats. The lesions were made by stereotaxic injection of quisqualic acid on postnatal days 14 (P14), 17 (P17), and 21 (P21). A marked loss of ChAT activity was found 7 days after surgery in all age groups of lesioned rats. Unoperated P14 rats were unable to perform the passive avoidance conditioned responses. Acquisition began on P17. Lesions made on P17 and P21 strongly impaired the acquisition and retention of the task, evaluated 7 days postoperation. No biochemical but a partial behavioral recovery was observed 3 months after surgery in rats lesioned on P14. On the contrary, despite a persistent decrease in cortical ChAT activity, rats lesioned on P21 were able to acquire and retain the passive avoidance conditioned response. These results indicate that destruction of NBM cholinergic neurons shortly after birth is not compensated for by the developmental plasticity of the residual neurons but results in permanent cholinergic hypofunction. They also demonstrate that cholinergic NBM neurons play an important role in the acquisition and retention of a passive avoidance task; nevertheless, a behavioral recovery may take place 3 months after the lesion, even in the presence of a persistent cholinergic hypofunction.

[The importance of histaminergic H1 and H2 receptors for the contractile effect of histamine on human umbilical veins]. / Znacenje histaminskih H1 i H2 receptora za kontraktilno djelovanje histamina na humanu umbilikalnu venu.

Influence of histamine and histaminergic H1 blockers (antazoline, promethazine) and H2 blockers (cimetidine, ranitidine) on isometric contraction of helically cut strips of human umbilical vein was examined. Histamine produced dose-related contraction of the vein strip, while histaminergic H1 and H2 blockers did not changed the tonus of the vein. The contractile activity of histamine was not influenced by cimetidine or ranitidine, while antazoline and promethazine antagonized mentioned activity of histamine completely. We suppose that histamine exerts contractile effect of human umbilical vein by acting on H1 receptors while H2 receptors are not involved in the mentioned activity of histamine.