Ataman Güre

Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production

Erythropoietin (EPO), produced by the kidney and fetal liver, is a cytokine-hormone that stimulates erythropoiesis under hypoxic conditions. It has been shown that EPO is produced in the central nervous system and its receptor is expressed on neurons. Since EPO has neuroprotective effects in vitro and in vivo against brain injury, we investigated the effect of EPO treatment on locomotor activities of animals, survival of nigral dopaminergic neurons and nitrate levels in substantia nigra and striatum in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of Parkinsonism in C57/BL mice. Our findings suggest that EPO has protective and treating effect in MPTP-induced neurotoxicity in this mouse model of Parkinsons Disease via increasing nitric oxide production.

Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum.

The administration of methamphetamine to experimental animals results in damage to nigrostriatal dopaminergic neurons. In the present study, we demonstrated that both the acute repeated and the chronic administration of methamphetamine causes an increase in thiobarbituric acid reactive substances, which are indicators of lipid peroxidation, and superoxide dismutase activity in the rat striatum. The results of present study strengthen the notion that reactive oxygen species may play an important role in the methamphetamine-induced neurotoxicity.

The effects of single dose of methamphetamine on lipid peroxidation levels in the rat striatum and prefrontal cortex

The administration of methamphetamine to experimental animals results in damage to dopaminergic neurons. In the present study, we demonstrated that a single dose (15 mg/kg) of methamphetamine results in production of oxidative stress as demonstrated by increased thiobarbituric acid reactive substances levels in the rat striatum and prefrontal cortex. In conclusion, the results of present study provide further evidence in support of the notion that oxidative stress may play an important role in the methamphetamine-induced neurotoxicity.

Methamphetamine causes depletion of glutathione and an increase in oxidized glutathione in the rat striatum and prefrontal cortex

The administration of methamphetamine to experimental animals results in damage to dopaminergic neurons. The hypothesis that methampheta-mine-induced neurotoxicity is mediated by reactive oxygen species was evaluated. It was found that acute administration of methamphetamine (5 and 15 mg kg-1) resulted in production of oxidative stress as demonstrated by decreased glutathione and increased oxidized glutathione levels in the rat striatum and prefrontal cortex. These changes in glutathione and oxidized glutathione levels were dose-dependent in striatum, but not in prefrontal cortex. In conclusion, the results of present study provide further evidence in support of the notion that oxidative stress may play an important role in the metham-phetamine-induced neurotoxicity.

The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model

1. We measured the ability of glucagon and amrinone, used alone and in combination, to improve the myocardial function in a rat isolated heart model of calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol consistently decreased heart rate and cardiac contractile force in our Langendorff rat isolated heart preparations. Glucagon increased the heart rate in a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(-1) mol concentration, and had no significant effect on cardiac contractility. 3. A positive linear correlation was found between the glucagon concentration and the percent recovery of baseline contractile force. 4. Although complete reversal of verapamil-induced myocardial depression occurred at glucagon concentrations of > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were administered together, there was no additional increase over glucagon alone in the increase in contractile force. 6. Glucagon, and not amrinone, is an appropriate agent, capable of reversing verapamil-induced myocardial toxicity in this rat isolated heart model. In vivo studies should be performed to assess whether this may be a reliable therapy in clinical cases.

Urinary N-acetyl-β-D-glucosaminidase activity in rabbits with experimental hypercalciuria

Abstract. Routinely used renal function tests remain normal in uncomplicated hypercalciuria. The aim of this study was to assess the value of N-acetyl-β-D-glucosaminidase (NAG), a sensitive marker of renal proximal tubular damage, in experimental hypercalciuria. Oral calcium providing 75 mg/kg per day elementary calcium and 20,000 IU/day vitamin D3 was administered for 15 days to 7 rabbits (Orytolagus cuniculus-New Zealand white) and 7 rabbits were given placebo as a control group. Serum calcium, phosphorus, and alkaline phosphatase, daily urinary calcium excretion and NAG/creatinine ratio were measured before and after drug administration. Kidneys were examined macroscopically and microscopically following the study period. Serum calcium, phosphorus and urinary calcium excretion increased, while alkaline phosphatase decreased significantly in response to drug treatment [10.8±1.5 vs. 12.2±1.3 mg/dl, 4.6±0.6 vs. 6.7±0.7 mg/dl, 22.3±8.3 vs. 46.8±22.5 mg/kg per day, and 138.0±57.1 vs. 70.1±33.1 IU/l, respectively (P <0.05)]. The NAG/creatinine ratio prior to the study (0.5±0.1 mU/mg) was significantly different from that after the study (5.4±1.5 mU/mg, P <0.01). In the control group, changes in serum and urinary parameters were not significant (P >0.05). The relationship between the urinary NAG/creatinine ratio and the daily urinary calcium excretion was statistically significant (r = 0.67, P <0.05). In the study group, nephrocalcinosis was present in all rabbits except 1 (85.7%), whereas none of the control group rabbits had nephrocalcinosis. In conclusion, in rabbits urinary NAG excretion increases significantly in nephrocalcinosis induced by hypercalciuria.

Prevention of Oral Dichlorvos Toxicity by Different Activated Charcoal Products in Mice

STUDY OBJECTIVE To determine whether immediate treatment with oral activated charcoal (AC) products of differing surface areas prevents clinical toxicity of a lethal oral dose of dichlorvos in mice. DESIGN An in vivo, prospective, randomized, placebo-controlled study using 75 male albino mice. INTERVENTIONS Fasting mice were administered 57.5 mg/kg of a 0.55% dichlorvos solution via feeding tube. One minute later, groups of 15 mice each received 1 or 2 g/kg of Actidose-Aqua AC or 1 or 2 g/kg of Sigma AC or sterile water by feeding tube. In this way, all mice received 15 mL/kg of an AC suspension or sterile water. The animals were observed for 24 hours for seizures or death. RESULTS In all treatment groups, mice were found to have significantly fewer seizures and deaths (P < .05) than the control group when compared by chi 2 and Fishers exact tests. No statistical difference was found between the death and seizure rates when treatment groups were compared with each other. The group sizes were too small, however, to rule out significant type II error (beta > .2). CONCLUSION In this in vivo mouse model, all AC products tested decreased the incidence of seizures and death. Further studies should be done to investigate the clinical effects of AC products with different surface areas.

Lung Clearance of Aerosolized 99mTc Erythromycin Lactobionate in Rabbits

In order to assess the lung clearance of aerosolized 99mTc Erythromycin Lactobionate (EL), 99mTc EL was administered to 9 New Zealand rabbits by inhalation. 5 rabbits inhaled cigarette smoke before 99mTc EL. Clearance half times were 3.0 +/- 0.9 hours in normals, 5.5 +/- 1.0 hours after smoke exposure. Clearance was not affected after destroying the surfactant layer. Slower clearance after smoke exposure may be due to the inhibition of mucociliary clearance. 99mTc EL can be considered as an alternative radioaerosol for ventilation imaging.

Does cisplatin chemotherapy decrease the MDP uptake of normal bone? An experimental study

ObjectiveBone scan is the accepted initial imaging modality for skeletal metastases. Cisplatin is a cell-cycle nonspecific antineoplastic agent used in some chemotherapy regimens. Knowing that platinum reacts with phosphate compounds such as methylenediphosphonic acid (MDP), decreases bone resorption and new bone formation, it can be proposed that cisplatin chemotherapy may decrease Tc-99m MDP bone uptake. We aimed to demonstrate, if present, the decrease in bone uptake and to determine the duration of this effect.MethodsThirty male Wistar rats were randomized into five groups, namely, placebo group (G1) and cisplatin groups (G2, G3, G4, G5). Pre-therapy bone scintigraphies were obtained in all the groups. Cisplatin chemotherapy was given as infusion. Post-therapy bone scintigraphies were obtained 10 min, 1 h, 24 h, and 72 h after chemotherapy in groups G2–G5, respectively. A placebo bone scintigraphy was obtained 10 min after infusion of serum physiologic in G1. Plasma samples for cisplatin plasma values were obtained. The graphite furnace atomic absorption spectrophotometry technique was used for cisplatin analysis. Quantitative analysis (bone uptake ratios) was performed by drawing regions of interest on the right femur, vertebral column, and adjacent soft tissues. The injection/examination time delay and the net injected MDP doses were also noted.ResultsThere was no statistically significant difference in bone uptake values, injected MDP doses or injection/examination time delay in any group. Cisplatin plasma values were significantly different in G2, G3, G4, and G5 (P < 0.05) but not in G1.ConclusionsCisplatin chemotherapy seems to have no effect on the Tc-99m MDP uptake of normal bone.

The effect of acute bilateral adrenalectomy on serotonin-induced inhibition of gastric acid secretion and acute gastric mucosal injury in rats

Serotonin (5‐hydroxytryptamine, 5‐HT) produces many changes in gastric functional parameters, including the inhibition of gastric acid secretion and changes in mucosal blood flow. Exogenous 5‐HT has also been shown to induce gastric erosion. The influence of adrenalectomy on experimental lesions in the rat gastric mucosa remains controversial. The aim of this study was to see the effects of adrenalectomy on pentagastrin stimulated gastric acid secretion in anaesthetized male Wistar rats. Gastric acid was collected via cannulae placed in the stomach. 5‐HT (3.5 μmol/kg, i.v.) inhibited pentagastrin stimulated acid output by 54% and produced haemorrhagic gastric lesions with a mean ulcer index of 2±0.3. Adrenalectomy prevented both 5‐HT induced inhibition of gastric acid secretion and mucosal injury. The results suggest that the effects of 5‐HT require an intact adrenal gland.