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Terzioglu B.,Pharmacology and Toxicology Unit | Berkman Z.,Haydarpasa Numune Research and Training Hospital
Journal of Research in Medical Sciences | Year: 2015

Background: Hyperglycemia is frequently encountered in critically ill patients and has been shown to contribute to both morbidity and mortality. We aimed to study the predictive role of blood glucose level in clinical outcomes of mechanically ventilated patients with traumatic brain injury during intensive care unit (ICU) stay and to explore its relationship with Glasgow coma scale (GCS) and acute physiology and chronic health examination (APACHE) II scores that are used in the evaluation of ICU patients as predictor. Materials and Methods: A total of 185 patients with craniocerebral trauma who were hospitalized in the ICU were included in the study. Comparisons of mean glucose values (MGVs) and APACHE II scores between survivors and nonsurvivors were made with Student’s t-test and chi-square test. Survival analysis was performed with log rank (Mantel-Cox) test and Cox regression was used for mortality risk factors analysis. Results: MGVs at the initial, last, and all measurements were significantly higher for nonsurvivors than for survivors. Hazard rate at any given time point for patients with mean glucose value (MGV) between 150 and 179 was found to be 3.691 times that of patients with MGV values between 110 and 149. The hazard rate at any given time point for patients with MGV values ≥180 was found to be 6.571 times that of patients with MGV values between 110 and 149. Conclusion: High glucose level is an independent risk factor for mortality in mechanically ventilated ICU patients with traumatic brain injury. © 2015 Journal of Research in Medical Sciences.

Karsli N.D.,Haydarpasa Numune Research | Subasi D.,Haydarpasa Numune Research | Terziolu B.,Pharmacology and Toxicology Unit | Turan G.,Haydarpasa Numune Research | Ekinci O.,Haydarpasa Numune Research
Drug Research | Year: 2014

Background: Levobupivacaine use is progressively increased for intrathecal anesthesia in transurethral resections. The aim was to determine ED50 and ED95 of intrathecal isobaric levobupivacaine by addition of 25mcg fentanyl for patients undergoing transurethral resections. Methods: A total of 100 patients undergoing transurethral resections with ASA I-III, were randomized to groups receiving intrathecal 0.5% isobaric levobupivacaine in doses of 6, 8, 10, 12 or 14mg in equal volumes with 25mcg intrathecal fentanyl addition. Sensorial block level was determined by pinprick and motor block by Bromage scale. Results: Mean onset time of sensorial block in 6mg group was significantly longer than that of sensorial block in 10mg, 12mg and 14mg groups (p<0.01), 8mg was longer than 12mg and 14mg (p<0.01), and 10mg onset time of sensorial block was significantly longer than 12mg and 14mg (p<0.01). Mean onset time of T10 sensory level in 6mg group was significantly longer than mean onset time of T10 sensory level in 10mg, 12mg and 14mg (p<0.01), the mean onset time of T10 sensory level in 8mg group was also significantly longer than that of 12mg, 14mg groups (p<0.01). ED50 and ED95 of levobupivacaine coadministered with 25 mcg fentanyl were 7.32mg and 10.88mg, respectively. Conclusion: Levobupivacaine with opioid co-administration can be used in doses considerably lower than doses proposed for routine use as it is a safe drug depending on its hemodynamic effects, side effects. © Georg Thieme Verlag KG Stuttgart New York.

Imbert L.,University of Limoges | Imbert L.,Pharmacology and Toxicology Unit | Boucher A.,Evaluation and Information Center for Drug Addiction | Delhome G.,Addictology Unit | And 8 more authors.
Journal of Analytical Toxicology | Year: 2014

Methoxetamine (MXE) is increasingly used and abused, as it is frequently presented as being safer than ketamine, and legal. Cases of only MXE consumption being associated with the occurrence of seizures are rarely reported. A single MXE intoxication case by inhalation is described concerning a 21-year-old man, not known to be epileptic, who was found collapsed in his bedroom, supposedly after an epileptic seizure. He was transferred to the Emergency Department of the Henri Mondor Hospital, Aurillac, France. He was conscious, but with a sinus bradycardia (48/min) and an ST-segment elevation on the electrocardiogram, and a slightly increased creatine kinase level (270 U/L) and hyponatremia (127 mmol/L). New seizure activity occurred during hospitalization, but the clinical course in the intensive care unit was favorable. Quantitation of MXE in serum and urine using gas chromatography coupled to mass spectrometry (GC-MS) was developed, as well as a liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) method for the determination of MXE in hair. Limits of detection and quantification were, respectively, 2 and 10 μg/L for the GC-MS method and both 0.5 pg/mg for the LC-MS-MS method. Concentrations of 30 and 408 mg/L were, respectively, measured in serum and urine. Concentrations of 135 and 145 pg/mg were detected in two 2.5 cm hair strands, consistent with one or several consumptions during the 2 1/2 months prior to sampling. A sample of the powder consumed was available and also analyzed. This case illustrates the dangers of this drug, which justify its classification as a narcotic in France since August 2013. © The Author 2014. Published by Oxford University Press. All rights reserved.

Stifanese R.,National Research Council Italy | Stifanese R.,University of Genoa | Averna M.,University of Genoa | De Tullio R.,University of Genoa | And 10 more authors.
Archives of Biochemistry and Biophysics | Year: 2014

Elevation in [Ca2+]i and activation of calpain-1 occur in central nervous system of SOD1G93A transgenic mice model of amyotrophic lateral sclerosis (ALS), but few data are available about the early stage of ALS. We here investigated the level of activation of the Ca2+-dependent protease calpain-1 in spinal cord of SOD1G93A mice to ascertain a possible role of the protease in the aetiology of ALS. Comparing the events occurring in the 120 day old mice, we found that [Ca2+]i and activation of calpain-1 were also increased in the spinal cord of 30 day old mice, as indicated by the digestion of some substrates of the protease such as nNOS, αII-spectrin, and the NR2B subunit of NMDA-R. However, the digestion pattern of these proteins suggests that calpain-1 may play different roles depending on the phase of ALS. In fact, in spinal cord of 30 day old mice, activation of calpain-1 produces high amounts of nNOS active species, while in 120 day old mice enhanced-prolonged activation of calpain-1 inactivates nNOS and down-regulates NR2B. Our data reveal a critical role of calpain-1 in the early phase and during progression of ALS, suggesting new therapeutic approaches to counteract its onset and fatal course. © 2014 Elsevier Inc. All rights reserved.

Terzioglu B.,Pharmacology and Toxicology Unit | Kaleli M.,Marmara University | Aydin B.,Marmara University | Ketenci S.,Marmara University | And 2 more authors.
Neurochemical Research | Year: 2013

The dysregulation of hypothalamic-pituitary-adrenal axis and noradrenergic, serotonergic and glutamatergic systems are thought to be involved in the pathophysiology of post-traumatic stress disorder. The effect of selective M1 muscarinic receptor antagonist, pirenzepine on anxiety indices was investigated by using elevated plus maze, following exposure to trauma reminder. Upon receiving the approval of ethics committee, Sprague-Dawley rats were exposed to dirty cat litter (trauma) for 10 min and 1 week later, the rats confronted to a trauma reminder (clean litter). The rats also received intraperitoneal pirenzepine (1 or 2 mg/kg/day) or saline for 8 days. Noradrenaline (NA) concentration in the rostral pons was analyzed by HPLC with electrochemical detection. The anxiety indices of the rats subjected to the trauma reminder were increased when compared to control rats (p < 0.05). Pirenzepine treatment in traumatized rats displayed similar anxiety indices of non-traumatized rats treated with physiological saline. Although freezing time was prolonged with pirenzepine in traumatized groups the change was not found statistically significant. The NA level was 1.5 ± 0.1 pg/mg in non-traumatized rats and increased to 2.4 ± 0.2 pg/mg in traumatized rats. Bonferroni post hoc test revealed that the NA content of the rostral pons of the traumatized rats treated with physiological saline was significantly higher than the content of other groups (p < 0.01). We conclude that NA content in the rostral pons increases in respect to confrontation to a trauma reminder which can be reversed by M1 antagonist pirenzepine indicating the roles of M1 receptors. © 2013 Springer Science+Business Media New York.

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