[Effects of harmane, norharmane and harmine on writhing behavior induced by acetic acid in mice]

The beta-carbolines harmane, harmine and norharmane are the members of Harmala,s alkaloids group [Peganum harmala, Zygophillaceae]. The beta-carboline alkaloids adjoined to benzodiazepine site of the gamma-aminobutyric acid type A [GABA[A]]. These alkaloids also inhibited cyclooxygenase and lipoxygenase activities. These findings showed that the beta-carbolines should be able to reduce writhing nociception induced by acetic acid- in mice. To assess the effects of acute treatment with harmane, norharmane and harmine on the writhing induced by acetic acid in mice. The experiments were carried out on male BALB/C mice [20-25g]. Intraperitoneal [I.p] injection of acetic acid [0.6%] was performed in order to cause writhing behavior. This behavior was recorded by direct observation for a 30-minutes period. Decrease of writhing count is indicative of an anti-nociception. In order to avoid the possibility of a physicochemical interaction between them, Drugs were administered on opposite sides of peritoned. Intraperitoneal [I.p] injection of Harmane [5-20mg/kg] on 6-9 mice, norharmane [5-15mg/kg] on 8-9 mice and harmine [10-15mg/kg] on 8-9 mice in per group decreased the writhing behavior significantly [P<0.0001, P<0.0003 and P<0.0016, respectively]. The inhibitory effects of the mentioned drugs were antagonized by flumazenil [2 mg/kg]. Effects of harmane, norharmane and harmine on writhing response may be mediated through an inverse agonistic mechanism located in the benzodiazepine receptors

Effect of L-arginine on neuromuscular transmission of the chick biventer cervicis muscle

NO is a short-lived gas molecule generated by degradation of L-arg to citrulline and by the activation of enzyme NOS Ca2+/calmodulin-dependent. There are multiple NOS isoforms that strongly are expressed in skeletal muscle, suggesting the crucial role of NO in regulating muscular metabolism and function. In this study, the effect of L-arginine was examined at the neuromuscular junction of the chick biventer cervicis muscle. Biventer cervicis muscle preparations from chick's age of 3 weeks were set up in the organ bath. The organ bath had a vessel with volume of about 70 ml; it contained Tyrode solution aerated with oxygen and was kept at 37°C. NO levels was also measured in the chick biventer cervicis muscle homogenates, using spectrophotometer method for the direct detection of NO, nitrite and nitrate. Total nitrite [nitrite+nitrate] was measured by a spectrophotometer at 540 nm after the conversion of nitrate to nitrite by copperized cadmium granules. L-Arginine at 500 micro g/ml, decreased twitch response to electrical stimulation, and produced rightward shift of the dose-response curve for acetylcholine or carbachol. L-arginine at 1000 micro g/ml produced a strong shift to the right of the dose-response curve for acetylcholine or carbachol with a reduction in efficacy. The inhibitory effect of L-arginine on the twitch response was blocked by caffeine [200 micro g/ml]. NO levels were found to be significantly increased in concentrations 500 and 1000 micro g/ml of L-arginine in comparison with the control group [p < 0.001]. These findings indicate a possible role of increased NO levels in the suppressive action of L-arginie on the twitch response. In addition, the results indicate that the post-junctional antagonistic action of L-arginine is probably the result of impaired sarcoplasmic reticulum [SR] Ca2+ release

[Elevated plasma copper/zinc ratios in patients with schizophrenia]

Copper and zinc, two essential trace elements, are neuroactive substances that can be synaptically released during neuronal activity. These metals have been implicated in diseases with neuropathological components, including Alzheimer's disease, Menkes disease, Wilson's disease, Pick's disease, stroke and seizures. Copper and zinc levels in body tissues reflect many physiological and pathological conditions, including dietary factors, hepatic disease, and acute and chronic infections. The purpose of the present study was to examine the plasma levels of copper [Cu] and zinc [Zn] in schizophrenic patients and to compare the Cu/Zn ratios with that of matched healthy subjects. Forty patients with schizophrenia [diagnosis were made according to DSM-IV] were sampled along with 50 healthy controls. Exclusion criteria included another concurrent psychiatric disorder, pregnancy, and medical disorders [endocrine, immune, liver cirrhosis, renal] or drugs [anticonvulsants, contraceptives, glucocorticoids] known to affect trace element metabolism. Fasting blood samples were withdrawn from an antecubital vein between 07.00 and 09.00 h. Plasma copper and zinc levels were measured using an atomic absorption spectrophotometer [Perkin Elmer GmbH, Uebelingen, Germany]. Two-tailed t test was used to determine statistical differences. All data were analyzed with the computer program, GRAPHPAD software [V2.01+]. Mean +/- SE of sera copper levels in cases and controls were 145 +/- 28 and 65 +/- 3 mg/dl respectively [P<0.05]. Also Mean +/- SE of sera zinc level in cases and controls were 67 +/- 2 and 81 +/- 4 mg/dl, respectively [P<0.05]. Cu/Zn ratios was 2.07 +/- 0.38 and 0.87 +/- 0.04 in cases and controls respectively [P<0.05]. There was a significant higher Cu/Zn ratio in schizophrenic patients compared to healthy subjects. These results suggest that Cu and Zn may be involved in the pathophysiology of schizophrenia

High-dose deferoxamine treatment [intravenous] for thalassaemia patients with cardiac complications

As a means to manage cardiac conditions, we determined the effects of high-dose intravenous [IV] deferoxamine in 15 thalassaemia patients with cardiomyopathy and high ferritin and haemoglobin levels. The patients received IV deferoxamine, 130 mg/kg per day over 10-14 hours [maximum 5 g] for 5 consecutive days. All patients underwent a full evaluation before receiving deferoxamine, and 2 days and 1 month after completing the treatment. Visual and auditory examinations were done to detect any side-effects. After treatment, cardiovascular symptoms decreased considerably and systolic function showed significant improvement, but there was no significant effect on diastolic function, electro-cardiography and physical findings. There were no significant side-effects reported

[Modification of naloxone-induced withdrawal signs by ascorbic acid in morphine-dependent guinea-pigs]

Ascorbic acid, an antioxidant vitamin, is found throughout the mammalian central nervous system. Although, the centeral role of ascorbic acid is unclear, but there is good evidence that ascorbic acid modulates opiate withdrawal syndrome. This study was done to determine the effect of ascorbic acid [A.A.] on naloxone-induced withdrawal signs in morphine-dependent guinea-pigs. In this experimental study, male guinea-pigs [300-400 g; 8-10 animals/group] were rendered dependent on morphine by subcutaneous [s.c.] injections of morphine sulfate 3 times a day for 3 days, and withdrawal signs were induced by intraperitoneal [i.p.] administration of naloxone [15 mg/kg] 2 h after the tenth injection of morphine sulfate on day 4; then animals were placed individually into a cylindrical glass [25 cm in diameter, 180 cm height] and the withdrawal signs were recorded over a 60-min period. Chronic pretreatment of guinea-pigs with A.A., 200 mg/kg, s.c. 3 times daily for 3 days, reduced withdrawal jumping, digging, writhing, rearing, face- washing, head and body shakes, penile licking and diarrhea. The mixed dopamine D1/D2 receptor agonist apomorphine [0.5 mg/kg, s.c.] markedly antagonized the inhibitory effect of A.A. on the withdrawal signs. The effect of apomorphine was blocked by the dopamine D1 receptor antagonist SCH23390 [0.5 and 1 mg/kg, i.p.] but not by the dopamine D2 receptor antagonist sulpiride [50 mg/kg, s.c.] nor the peripheral dopamine receptor antagonist domperidone [1 mg/kg, s.c.]. It is concluded that chronic administration of ascorbic acid inhibits opiate withdrawal, via a central dopamine D1 receptor mechanism

[Comparison of the effects of different doses of ketamine propofol on haemodynamic changes of the patients during induction of anesthesia]

The aim of this prospective, clinical trial study was to investigate whether the administration of different doses of ketamine before induction with propofol imporves its associated haemodynamic propofol during induction and tracheal intubation. One hundered and thirty adult patients ASA I were randomly allocated to one of six groups to receive either propofol 2 mg/kg [n= 23], propofol 1.75 mg/kg with ketamine 0.25 mg/kg [n=21], propofol 1.5 mg/kg with ketamine 0.5 mg/kg [n=20], propofol 1.25 mg/kg with ketamine 0.75 mg/kg [n=21], propofol 1 mg/kg with ketamine 1 mg/kg [n=24], and ketamine group alone 2 mg/kg [n=21]. Ketamine was administered prior to induction with propofol, relaxant and tracheal intubaion. Systolic, diastolic pressure and heart rate were automatically recorded before induction [Baseline], immediately after induction, and 1, 5 and 10 min after tracheal intubation by Armita devices. Systolic, diastolic pressure and palse rate were not significantly different in different groups befor the induction. However theses difference were significant after the induction of anesthesia [P<0.001]. The highest increase and decrease in blood pressure occurred in ketamine and propofol groups respectively. Haemodynamic stability was much better in patients anesthetized using propofol plus 0.5 to 0.75 mg/kg ketamine. We conclude that the addition of ketamine 0.5 and 0.75 mg/kg improves haemodynamics when compared to ketamine 2 mg/kg alone or propofol 2 mg/kg during induction of anesthesia

[Effect of Dextromethorphan on Apomorphine induced licking behavior in rat]

Dextromethorphan is a NMDA receptor antagonist in the glutamatergic system. Currently, there are reports showing that the glutamatergic NMDA receptor mechanism stimulates dopamine release from several brain regions. This effect may modulate the stereotyped behaviors of dopaminergic system. The purpose of this study was to determine the interaction between dextromethorphan and stereotyped licking behavior in rats. In the present study, effects of dextromethorphan and different dopamine receptor antagonists on apomorphine-induced licking behavior were examined. For the induction of licking, the dose of 0.5 mg/kg, s.c. of apomorphine was used. Dextromethorphan [10-30 mg/kg, i.p.] dependently reduced the licking behavior. Intraperitoneal injection-of dextromethorphan [15 mg/kg, ED50] potentiated the inhibitory effects of low doses of the dopamine D1 receptor antagonist, SCH 23390 [0.00625 and 0.0125 mg/kg, i.p.] and the dopamine D2 receptor antagonist, pimozide [0.5-1 mg/kg, i.p]. These results suggest that the inhibitory effect of dextromethorphan on apomorphine induced licking behavior is mediated via a doparnine Dl receptor mechanism

[Evaluation of antidepressant activities of rose oil and geranium oil in the mouse forced swim test]

Depression is one of the most common psychiatric disorders that results in significant consequences in active population of the society. In traditional manuscripts, there are many indications about the antidepressant effects of rose oil. The purpose of this study was to determine the antidepressant effects of rose oil and geranium oil. All experiments were carried out on male Swiss-Webster mice [25-30 gr]. The antidepressant activities of rose oil and geranium oil were assesed using the forced swim test. In this test, mice were placed into a cylinderical glass [25 cm height, 12 cm in diameter] containing a column of 17 cm of water at 25 +/- 1 degree C. After 30 min [for the injection route] or 2 weeks [for the oral route] of the rose oil and geranium oil administrations, the mice were subjected to forced swimming test for 8 min. Acute subcutaneous [s.c.] injection or chronic oral administration of rose oil and geranium oil significantly decreased the immobility time in the mouse forced swim test. The geranium oil response was biphasic. Pretreatment of animals with amphetamine and nortriptyline also reduced the immobility time. The inhibitory effects elicited by rose oil, geranium oil and amphetamine but not nortriptyline were antagonized by reserpine. The results suggest that the antidepressant activities of rose oil and geranium oil may be mediated through a presynaptic mechanism

[Evaluation of antidepressant activities of harmane, norharman and harmine in mice]

It has been reported that, the [R]-carboline alkaloids of peganum harmala seeds have a stimulatory action on serotonin and catecholamines releases in different brain regions. In addition, one of the most important pharmacological effects demonstrated for [R]- carbolines is a revesible inhibitory action on MAO-A. These findings suggest that - carbolines, should alleviate at least some of the signs of depression. The purpose of present study is to determine the antidepressant activity of [R]-carbolines harmane, norharmane and harmine. All experiments were carried out on male Swiss-Webster mice [25-30g]. The antidepressant activities of the [R]-carbolines were assessed using the forced swim test. This test is the most widely used tool for antidepressant activity preclinically. In this test, mice were placed into a cylinderical glass [25 cm height, 12 cm in diameter] containing a column of 15 cm of water at 25 +/- 1 [o]C. After 30 min of the-carbolines injections, the mice were subjected to forced swimming test for 8 min and their immobility time was recorded. Intraperitoneal [i.p.] injections of harmane [5-15 mg/kg], norharmane [2.5-10 mg/kg] and harmine [5-15 mg/kg] significantly decreased the immobility time in the mouse forced swim test. The inhibitory effects of harmane, norharmane and harmine were antagonized by flumazenil [5 mg/kg, i.p.] but not by reserpine [5 mg/kg, i.p., 18 h before test]. The results suggest that the antidepressant activities of harmane, norharmane and harmine may be mediated through an inverse agonistic mechanism