Perceptions of students in different phases of medical education of educational environment: ankara university faculty of medicine.

The present study was undertaken to identify the perceptions of students about their educational environment in a newly restructured curriculum. The Turkish version of the DREEM questionnaire (total score: 200) was used to diagnose the strengths and weaknesses of the curriculum which is known to be a major determinant of educational environment. Five hundred fifty three students (years 1, 3, 5) voluntarily replied to the questionnaire. The mean DREEM score was found to be 117.63 (58.8%). The mean scores for the whole DREEM questionnaire and the five essential domains were found to be significantly different in different phases of medical education. The scores were found to be highest (123.65) for year 3 students and lowest (109.39) for year 5 students. The results are the first data of a curriculum reform obtained from the students about the educational environment and give important feedback to curriculum planners and change managers of the faculty for necessary improvement.

Pharmacological characterization of metamizol-induced relaxation in phenylephrine-precontracted rabbit thoracic aorta smooth muscle.

Metamizol produced a dose- and time-dependent relaxation in rabbit thoracic aorta smooth muscle that was precontracted by phenylephrine. Such a relaxation was not observed with indomethacin, which is also a nonsteroidal anti-inflammatory drug. The relaxing effect of metamizol was independent of the presence of vascular endothelium. Tetraethylammonium (a calcium-activated potassium channel inhibitor), glybenclamide (an ATP-dependent potassium channel inhibitor), indomethacin (a cyclooxygenase inhibitor), and methylene blue (a soluble guanylate cyclase inhibitor) did not have any effect on metamizol-induced relaxation response. Metamizol did not produce any relaxation effect on aortic smooth muscle when KCl (30, 60, and 117 mM KCl) was used instead of phenylephrine to precontract the preparation. Ouabain (a Na-K ATPase pump inhibitor) showed a dose-dependent inhibition on metamizol's relaxation response. However, in potassium-free medium, which is an alternative way to block the Na-K ATPase pump, no inhibition in metamizol-induced relaxation response was observed. When metamizol was incubated for 2 h in organ-bath conditions before evaluating its relaxing effect, it produced a relatively faster relaxation, indicating that the relaxing effect of metamizol is produced by one of its (active) spontaneous degradation products (possibly 4-methylaminoantipyrine).

The effects of flumazenil on two way active avoidance and locomotor activity in diazepam-treated rats.

The present study was undertaken to determine the effects of chronic flumazenil treatment alone and simultaneously with diazepam on acquisition performance in an active-avoidance task and on locomotor activity in rats. Flumazenil (5, 10 and 20 mg/kg) and diazepam (0,5, 1.0 and 2.0 mg/kg) were administered intraperitoneally to rats before each daily training session for 5 days. The baseline of avoidance performance was set to approximately 50% and responses were expressed as acquisition rate. Locomotor activity of the rats was simultaneously recorded but only following the first training session. Diazepam decreased acquisition rate between the dose range used. Flumazenil had no effect on the acquisition rate of naive rats but reversed low dose diazepam-induced learning and memory impairment. Diazepam induced locomotor depression within the same dose range that decreased acquisition rate. Flumazenil had no effect on locomotor activity, but reversed the locomotor depressant effect of diazepam. The striking contradiction with previous data that flumazenil has no effect on learning-memory processing is discussed.

Melperone treatment in an organic delusional syndrome induced by hyperprolactinemia: a case report.

A young female with organic delusional syndrome induced by hyperprolactinemia was admitted to the Psychiatry Clinic of Ankara Social Security Hospital. The most striking characteristic of her history was either worsening of the endocrinologic clinical outcome under conventional neuroleptic treatment or worsening of clinical psychiatric outcome under bromocriptine therapy. A new atypical neuroleptic, melperone, suggested to minimally affect plasma prolactin levels, was started. Her psychotic complaints significantly subsided and she was devoid of any symptomatological change regarding her endocrinological status. These results were discussed.

Antiseizure activity of insulin: insulin inhibits pentylenetetrazole, penicillin and kainic acid-induced seizures in rats.

The present study was undertaken to evaluate the antiseizure activity spectrum of insulin against various behavioral seizure models in rats. Insulin was injected intraperitoneally (i.p.) at a test dose of 1 U/kg. Dextrose (3 g/kg) was administered simultaneously with insulin to counteract its hypoglycemic effect and induce a normoglycemic state. Insulin was found to significantly decrease the incidence, intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by pentylenetetrazole (60 mg/kg i.p.) and significantly decrease the intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by penicillin (2000 U/intracerebrocortical). Insulin was not only found to prolong the latency of all the seizure components but was found to reduce the incidence of focal myoclonic twitches and generalized tonic-clonic convulsions induced by kainic acid (12 mg/kg i.p.) as well. Insulin was shown to be ineffective to suppress ouabain (5 micrograms/intracerebroventricular) induced seizures. These findings indicate that insulin possesses a broad spectrum of antiseizure activity in rats. Interaction with brain Na(+)-K(+)-ATPase has been discussed as a possible mechanism of action.

Investigation of the effects of moclobemide in chronic ethanol feeding rats.

Effects of chronic moclobemide administration on ethanol consumption, blood ethanol level, motor coordination and seizures induced by an audiogenic stimulus during ethanol withdrawal syndrome have been investigated in chronically ethanol intoxicated rats. Adult male Wistar rats (211-289 g) were used. Ethanol (7.2% v/v) was given to rats by a special liquid diet for 15 days. Moclobemide (10, 30 and 45 mg kg-1) or saline was injected to ethanol-feeding rats subcutaneously through 15 days. Daily ethanol intake and body weight gain of the rats were recorded. Blood ethanol levels were measured in rats given saline or chronic moclobemide (30 mg kg-1) just before and 6 h after ethanol withdrawal. At the sixth hour of the ethanol withdrawal, the incidence, intensity and latency of the seizures induced by an audiogenic stimulus were recorded in saline and acute (30 mg kg-1) or chronic (10, 30 and 45 mg kg-1) moclobemide-administered rats. Accelerod performances of the chronic moclobemide (45 mg kg-1) or saline injected rats were also evaluated. The mean ethanol intake of the rats ranged from 10.06 to 15.63 g kg-1 day-1 during the study. Chronic moclobemide treatment did not occur any significant effect on daily ethanol consumption, ethanol clearance and accelerod performances of the rats. No significant changes on the incidence, intensity and the latency of the audiogenic seizures were also observed. Our results suggest that there has been no adverse interaction between ethanol and moclobemide.

Behavioural assessment of pinealectomy and foetal pineal gland transplantation in rats: Part II.

Pineal gland is an endocrine organ which exerts regulatory effects on the activity of various organs and systems. The present study was undertaken to highlight in experimental animals the possible integrative function of this endocrine organ on a behavioural pattern. Pinealectomy and foetal pineal gland transplantation to a subpial cortical area close to the pinealectomized region was performed. Behaviour was defined through motor activity induced by low (2 mg/kg) and high (10 mg/kg) doses of amphetamine in rats. It was shown that pinealectomy produced significant different patterns of behaviour induced by low and high doses of amphetamine. In sham operated animals low dose amphetamine induced a significant locomotor stimulation but without stereotyped activity. High dose amphetamine induced stereotyped activity. After pinealectomy even low dose amphetamine produced the behavioural pattern of stereotyped activity resembling a high dose amphetamine-induced behaviour. This differential effect of amphetamine, seen in pinealectomized rats, was completely restored after transplantation. On the other hand, melatonin treatment did not generate a significant alteration of behavioural profile either in the control or pinealectomized group of rats. Results are discussed with regard to the general regulatory function of the pineal gland.

Iloprost, a stable analogue of PGI2, potentiates the hyperthermic effect of PGE2 in rats.

Centrally mediated effects of iloprost, a stable analogue of PGI2, on rectal temperature have been investigated in conscious rats. ICV administration of iloprost (100-1,000 ng, ICV) produced a dose-dependent, monophasic hyperthermic response that was not inhibited by indomethacin. When injected into the preoptic anterior hypothalamic (POAH) region, iloprost (2-50 ng/POAH) induced a biphasic increase in rectal temperature. While the first phase was inhibited by AH 6809, an E1-type prostaglandin (EP1) receptor antagonist, the second phase was abolished by indomethacin pretreatment. Iloprost was found not to alter rectal temperature when injected into the ventromedial hypothalamic area. Administration of iloprost into the POAH in a dose that had no effect on rectal temperature significantly potentiated the hyperthermic effect of PGE2 (50 ng, ICV). These findings suggest that the pyrogenic effect of iloprost is partly mediated by EP1 receptors located on the POAH. Regarding the similarities of iloprost and PGI2, it is further proposed that endogenous PGI2 might act to modulate hyperthermic effect of PGE2 released during arachidonic acid- or endogenous pyrogen-induced fever.

Effects of intracerebral iloprost injections on motor activity and chemically-induced seizures in rats.

The effects of iloprost, a chemically stable analog of prostacyclin, on motor activity, pentylenetetrazol (PTZ)- and strychnine (ST)-induced seizures were studied in rats. Depression on motor activity was observed after a 500 ng/icv dose. Thus, both spontaneous locomotor activity and exploratory behavior were significantly reduced. While iloprost was ineffective against ST-induced seizures, it produced dose-dependent inhibition of PTZ-induced seizures. ED50 (95% confidence limits) value of iloprost for the suppression of clonic convulsions induced by PTZ was 224.96 (100.43-504.00) ng/icv. Anticonvulsive effect of iloprost was significantly potentiated by clonazepam pretreatment. In this case ED50 of iloprost was 39.40 (23.88-65.01) ng/icv. Unilateral iloprost injections into substantia nigra pars reticulata in a relatively lower dose range (0.5-2.0 ng/ic) also dose-dependently inhibited PTZ-induced seizures. In comparison to other prostanoids iloprost seems to have more potent and selective anticonvulsive activity against PTZ-induced seizures without marked motor depressant action in rats. It is further suggested that antiseizure effect of iloprost might be mediated by GABAergic inhibitory mechanisms.

Iloprost-induced writhing in mice and its suppression by morphine.

Intraperitoneally (i.p.) administered iloprost produced a writhing response indicating nociception. This effect induced by 4 micrograms/kg iloprost was dose dependently protected by morphine with an ED50 (95% confidence limits) value of 0.039 (0.0018-0.067) mg/kg. On the other hand, indomethacin had no effect on iloprost-induced writhing. Thus, this effect of iloprost seems to be relatively more sensitive than other irritants-induced responses on determining the analgesic potency of narcotic drugs.

The possible role of benzodiazepine receptors in morphine analgesia.

Diazepam within its therapeutic dose range, was shown to have no effect on nociception, but was shown to antagonize the analgesic action of morphine. This antagonism was found to be statistically significant at 0.5 mg/kg diazepam. To elucidate the mechanism of this inhibitory action of diazepam against morphine analgesia, Ro 15-1788, the specific antagonist of benzodiazepine receptors was used. As a result, Ro 15-1788 was found to partially reverse the inhibitory action of diazepam against morphine analgesia. This overall interaction between the supramolecular GABA receptor complex and morphine is discussed.

The possible modulation of morphine analgesia by the supramolecular GABA receptor complex.

In the present study, the mechanism of the antagonistic action of 0.5 mg/kg diazepam on the analgesic effect of morphine was investigated. While Ro 15-1788, a benzodiazepine receptor antagonist, was found to partially reverse the inhibitory action of diazepam on morphine analgesia, a chloride channel blocking agent, picrotoxin, produced complete antagonism of the action of diazepam. Furthermore, picrotoxin potentiated the partial antagonistic effect of Ro 15-1788 at a normally ineffective dose to affect the 0.5 mg/kg diazepam-morphine dose-response curve. These overall effects of picrotoxin on the supramolecular GABA receptor complex are discussed.

A new method for the rapid measurement of analgesic activity in rabbits.

A simple and rapid method is described for the screening of narcotic and non-narcotic analgesics in conscious rabbits. This method is based upon the increase in threshold by electrical stimulation of the ears of rabbit, by analgesics. A reliable dose-response and time-response relations were observed for both groups of analgesics. Naloxone did not produce a hyperalgesia when given alone. It antagonized, however, the analgesic activity of morphine without altering that of aspirin. From these results it is concluded that nociception induced by electrical stimulation of rabbit ears is a simple and rapid method for the screening of analgesics as well as their interactions with specific antagonists.

The effects of morphine and delta-9-tetrahydrocannabinol on motor activity in rats.

Acute treatment of rats either by high doses of morphine or delta 9-tetrahydrocannabinol (THC) decreased locomotor activity. Naloxone reversed morphine-induced depression completely and reversed THC-induced depression only partially. On day 3 of treatment, tolerance developed to the locomotor inhibitory action of THC or morphine and partial cross-tolerance was observed to the depressant action of THC. Naloxone slightly depressed locomotor activity in THC-tolerant rats, but increased motor activity in morphine-tolerant rats.

Antagonism by chlornaltrexamine of some effects of delta 9-tetrahydrocannabinol in rats.

Chlornaltrexamine (beta-CNA) a selective, long-acting irreversible opiate antagonist inhibited the analgesia, hypothermia, hypothermia tolerance and physical dependence produced by delta 9-tetrahydrocannabinol (THC) in rats. The results suggest that there are some common features between cannabis and opiates and some actions of THC may be mediated by opioid related mechanisms in the central nervous system.

Correlation between the dose and development of acute tolerance to the hypothermic effect of THC.

The administration of 0.3-40 mg/kg delta 9-tetrahydrocannabinol (THC) produced a dose-dependent hypothermia in rats. The maximal hypothermic effect was obtained with the dose of 2.5 mg/kg of THC. When the same doses of THC were repeated on days 2 and 3, tolerance to the hypothermic effect of THC was apparent. Doses of THC higher than 2.5 mg/kg induced a significant and dose-dependent tolerance after the first administration whereas with the lower doses, tolerance was only apparent after the second injection. The possible mechanism of these effects of THC is discussed.

Effect of delta 9-tetrahydrocannabinol on the morphine-induced hyperactivity of mice.

The effect of delta 9-tetrahydrocannabinol (THC) on the locomotor activity-stimulating action of morphine has been investigated in mice. THC (10 mg/kg) has been found to potentiate morphine-induced hyperactivity. On the other hand, the stimulating action of morphine on motor activity strongly diminished in mice rendered tolerant by the implantation of a morphine pellet. The pretreatment of morphine-tolerant mice with the same dose of THC did not change the effect of morphine on the motor activity. These results suggest that tolerance also developed to the potentiating action of THC on morphine-induced hyperactivity during the development of tolerance to this action of morphine.

Interaction between delta 9-tetrahydrocannabinol and morphine on the motor activity of mice.

The present experiments dealt the effects of delta 9-tetrahydrocannabinol (THC) on the locomotor activity stimulating action of morphine in mice. In the first series of experiments, the pretreatments of mice by THC in doses up to 20 mg/kg have been found to potentiate the morphine-induced hyperactivity in dose-dependent manner, but higher doses of THC did not produce such an action. In the second series of experiments the dose-response curve of morphine for the motor activity has been found to shift to the left by the pretreatment of mice with 10 mg/kg of THC. These results show a synergism between morphine and THC and suggest that both drugs may share some common site of action.