Aging protects rat cortical slices against to oxygen-glucose deprivation induced damage.

Objective: In present study, we aimed to clarify effect of aging on the susceptibility of brain tissue to neurodegeneration induced by ischemia.Methods: Damage induced by oxygen-glucose deprivation (OGD) followed by reoxygenation (REO) were compared in cortical slices prepared from young (3 months of age) and aged (22-24 months of age) male Sprague Dawley rats.Results: After incubation of the slices in an oxygen and glucose containing control condition, 2,3,5-triphenyl tetrazolium chloride (TTC) staining intensity was found significantly high in aged cortical slices. Although thirty minutes incubation of the slices in OGD medium followed by REO (OGD-REO) caused similar decline in TTC staining in young and aged cortical slices, staining intensity was still significantly higher in the slices prepared from aged animals. Thirty minutes of OGD-REO, on the other hand, also caused more increase in lactate dehydrogenase (LDH) leakage from young slices. While water contents of the slices were almost equal under control condition, it was significantly high in young cortical slices after OGD-REO incubations. In contrary to these findings, OGD and REO caused more increases in S100B output from aged rat cortical slices. S100B levels in brain regions including the cerebral cortex were also found higher in aged rats.Conclusion: All these results indicate that, cortical slices prepared from aged male rats are significantly less responsive to in vitro OGD-REO induced alterations. Since protein S100B outputs were almost doubled from aged cortical slices, a possible involvement of this enhanced S100B output seems to be likely.

Protective Effects of Chlorogenic Acid and its Metabolites on Hydrogen Peroxide-Induced Alterations in Rat Brain Slices: A Comparative Study with Resveratrol.

The effectiveness of chlorogenic acid and its main metabolites, caffeic and quinic acids, against oxidative stress was investigated. Resveratrol, another natural phenolic compound, was also tested for comparison. Rat cortical slices were incubated with 200 µM H2O2 for 1 h, and alterations in oxidative stress parameters, such as 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the production of both malondialdehyde (MDA) and reactive oxygen species (ROS), were assayed in the absence or presence of phenolic compounds. Additionally, the effectiveness of chlorogenic acid and other compounds on H2O2-induced increases in fluorescence intensities were also compared in slice-free incubation medium. Although quinic acid failed, chlorogenic and caffeic acids significantly ameliorated the H2O2-induced decline in TTC staining intensities. Although resveratrol also caused an increase in staining intensity, its effect was not dose-dependent; the high concentrations of resveratrol tested in the present study (10 and 100 µM) further lessened the staining of the slices. Additionally, all phenolic compounds significantly attenuated the H2O2-induced increases in MDA and ROS levels in cortical slices. When the IC50 values were compared to H2O2-induced alterations, chlorogenic acid was more potent than either its metabolites or resveratrol for all parameters studied under these experimental conditions. In slice-free experimental conditions, on the other hand, chlorogenic and caffeic acids significantly attenuated the fluorescence emission enhanced by H2O2 with a similar order of potency to that obtained in slice-containing physiological medium. These results indicate that chlorogenic acid is a more potent phenolic compound than resveratrol and its main metabolites caffeic and quinic acids against H2O2-induced alterations in oxidative stress parameters in rat cortical slices.

High glutamate attenuates S100B and LDH outputs from rat cortical slices enhanced by either oxygen-glucose deprivation or menadione.

One hour incubation of rat cortical slices in a medium without oxygen and glucose (oxygen-glucose deprivation, OGD) increased S100B release to 6.53 ± 0.3 ng/ml/mg protein from its control value of 3.61 ± 0.2 ng/ml/mg protein. When these slices were then transferred to a medium containing oxygen and glucose (reoxygenation, REO), S100B release rose to 344 % of its control value. REO also caused 192 % increase in lactate dehydrogenase (LDH) leakage. Glutamate added at millimolar concentration into the medium decreased OGD or REO-induced S100B release and REO-induced LDH leakage. Alpha-ketoglutarate, a metabolic product of glutamate, was found to be as effective as glutamate in decreasing the S100B and LDH outputs. Similarly lactate, 2-ketobutyrate and ethyl pyruvate, a lipophilic derivative of pyruvate, also exerted a glutamate-like effect on S100B and LDH outputs. Preincubation with menadione, which produces H2O2 intracellularly, significantly increased S100B and LDH levels in normoxic medium. All drugs tested in the present study, with the exception of pyruvate, showed a complete protection against menadione preincubation. Additionally, each OGD-REO, menadione or H2O2-induced mitochondrial energy impairments determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and OGD-REO or menadione-induced increases in reactive oxygen substances (ROS) determined by 2,7-dichlorofluorescin diacetate (DCFH-DA) were also recovered by glutamate. Interestingly, H2O2-induced increase in fluorescence intensity derived from DCFH-DA in a slice-free physiological medium was attenuated significantly by glutamate and alpha-keto acids. All these drug actions support the conclusion that high glutamate, such as alpha-ketoglutarate and other keto acids, protects the slices against OGD- and REO-induced S100B and LDH outputs probably by scavenging ROS in addition to its energy substrate metabolite property.

Intramuscular tramadol vs. diclofenac sodium for the treatment of acute migraine attacks in emergency department: a prospective, randomised, double-blind study.

The aim of this prospective, randomised, double-blind study was to evaluate the efficacy of intramuscular (IM) tramadol 100 mg in emergency department treatment of acute migraine attack and to compare it with that of IM diclofenac sodium 75 mg. Forty patients who were admitted to our emergency department with acute migraine attack according to the International Headache Society criteria were included in the study. Patients were randomised to receive either tramadol 100 mg (n=20) or diclofenac sodium 75 mg (n=20) intramuscularly. Patients rated their pain on a four-point verbal scale (0=none, 1=mild, 2=moderate, 3=severe) at the beginning of the trial and at 30, 60, 90 and 120 min. At each time interval, severity of associated symptoms were also questioned and recorded. Global evaluation of the drugs by patients and doctors were also recorded. Patients were also asked if they would prefer the same injection in future visits. Any adverse events, whether related to the drug or not, were also recorded. Patients were followed up by telephone 48 h later to check for any headache recurrence. Two-hour pain response rate, which was the primary endpoint, was 80% for both tramadol and diclofenac groups. There were no statistically significant differences among groups in terms of 48-h pain response, rescue treatment, associated symptoms' response, headache recurrence and adverse event rates. Fifteen (75%) patients in the tramadol group and 16 (80%) patients in the diclofenac group stated that they may prefer the same agent for future admissions. In selected patients, tramadol 100 mg IM may be an effective and reliable alternative treatment choice in acute migraine attacks.

Analysis of the outcomes of cardiopulmonary resuscitation in an emergency department.

OBJECTIVE: The aim of this study is to analyse the factors affecting emergency department (ED) cardiopulmonary resuscitation (CPR) outcome. METHODS: A standard CPR protocol was performed in all patients and certain pre and postresuscitation parameters including age, sex, initial arrest rhythm, primary underlying disease, initiation time of advanced cardiac life support, duration of return of spontaneous circulation were recorded. Patients were followed up to determine rates of successful CPR, survival and one-year survival. RESULTS: From December 1999 to May 2001, 80 consecutive adult patients in whom a standard CPR was performed in the ED were prospectively included in the study. The overall rate for successful CPR, survival and one-year survival were found to be 58.8% (47/80), 15% (12/80) and 10% (8/80), respectively. Survival and one-year survival rates were better in patients with an initial arrest rhythm of ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) than both pulseless electrical activity (pEA) and asystole; survival and one-year survival rates were better in patients with a primary underlying disease of cardiac origin than non-cardiac origin. Acute myocardial infarction had the best prognosis among conditions causing arrest. Presence of sudden death was found to have a better survival and one-year survival rate. CONCLUSION: Initial cardiac rhythm of VF/pVT, cardiac origin as the primary disease causing cardiopulmonary arrest and presence of sudden death were found to be good prognostic factors in CPR.