Berna Terzioglu

Fatigue of cholestasis and the serotoninergic neurotransmitter system in the rat

Fatigue associated with cholestasis may impair health‐related quality of life. The pathogenesis of this symptom is largely unknown, but it has been suggested that central serotoninergic neurotransmission may be implicated and that serotonin 1A receptor agonists may yield improvement. The aim of this study was to study the central serotoninergic system, specifically the serotonin (5‐HT)1A receptor–mediated pathway of serotoninergic neurotransmission, in a bile duct resection rat model of cholestasis. Fatigue was assessed in the forced swim test in sham and bile duct–resected rats. The serotonin behavioral syndrome, which includes hyperlocomotion, was assessed in both groups of rats after escalating doses of the 5‐HT1A receptor agonist 8‐hydroxy(di‐n‐propylamine)tetralin (8‐OH DPAT). 5‐HT1A and 5‐HT2 receptor densities were explored in four brain regions using a receptor‐binding assay. Extracellular 5‐HT and 5‐hydroxyindoleacetic acid were measured via in vivo brain dialysis. Bile duct–resected rats spent more time floating in the forced swim test, and 8‐OH DPAT decreased floating time in cholestatic rats (P < .01). Dose–response curves created with 8‐OH DPAT for the serotonin behavioral syndrome were similar in bile duct–resected and sham‐operated rats. 5‐HT1A and 5‐HT2 receptor densities in most brain regions and extracellular serotonin levels were similar in both groups of rats. In conclusion, 5‐HT1A receptor agonist–induced amelioration of fatigue in cholestatic rats may be nonspecific and not linked to reversal of the pathophysiology of fatigue associated with cholestasis; however, these data do not exclude a potential role of the central serotoninergic system in the evolution of fatigue. (HEPATOLOGY 2005.)

Anticonvulsant activity of 3,5-dimethylpyrazole derivatives in animal models

A series of 3,5-dimethylpyrazole derivatives, structurally related to the previously described potent ameltolide analogues, were synthesized and evaluated for their anticonvulsant activity. Ten compounds were prepared by reacting the 4-amino-3,5-dimethylpyrazole with appropriate substituted carboxylic acids, benzoyl chlorides and benzaldehydes to obtain amide and imine derivatives. Initial anticonvulsant screening was performed using intraperitoneal pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizure tests in mice. Among the 10 tested compounds, N-[1-(4-methoxybenzoyl)-3,5-dimethylpyrazole-4-yl]-4-methoxybenzamide 2 and N-[1-(2,6-dichlorobenzoyl)-3,5-dimethylpyrazole-4-yl]-2,6-dichlorobenzamide 3 decreased seizure severity and the mortality rate in the PTZ test. Hence, compound 3 was tested in an animal model of absence epilepsy, Genetic Absence Epileptic Rats from Strasbourg (GAERS). There were no significant changes in the duration or number of spike-and-wave discharges in this model.

Treatment of Lateral Epicondylitis Using Betahistine Dihydrochloride

Objectives Lateral epicondylitis is a commonly encountered problem. Disruption of microcirculation is hypothesized in the pathophysiology of lateral epicondylitis. Betahistine dihydrochloride [BHD] is used in our study for its microcirculation increasing activity. Methods After hospital ethics committee approval and getting written informed consent from patients, adult patients with lateral epicondylitis were recruited in this randomized study. One group received 48 mg/day BHD for 10 days. The control group received 750 mg/day naproxen sodium [NS] for 10 days. Visual Analog Scale [VAS] and Verhaar criteria were evaluated before and after treatment. Results Fifty-five patients [41 females, 14 males], mean age 40 years [21–63 years] participated. The VAS before treatment was not significantly different between groups. In the NS group, mean VAS after the 10th day, third month, and sixth month were found to be significantly higher than that of the BHD group [P = 0.0001]. Verhaar criteria after the 10th day of treatment in the BHD group were significantly improved when compared with the NS group [P = 0.008]. Evaluation of clinical findings showed no difference between groups before treatment, but 10th day, third, and sixth month symptoms were found to be lesser in the BHD group when compared with the NS group [P = 0.001; P = 0.001; P = 0.001, respectively]. Conclusions The microcirculation increasing agent BHD restored the signs and symptoms of lateral epicondylitis. In conclusion BHD, which is a histamine agonist, is a favorable choice in the treatment of lateral epicondylitis.

Escitalopram increases cortical nitric oxide synthase (NOS) in rat brain during ethanol withdrawal.

The effect of escitalopram on ethanol withdrawal syndrome (EWS) and involvement of nitric oxide system in rats was investigated. Male Wistar rats divided into five experimental groups of eight animals each: (a) control group; (b) EWS (saline) group; (c) escitalopram 2.5 mg group; (d) escitalopram 5mg group and (e) escitalopram 10 mg group. Ethanol dependence was induced in rats by ethanol-containing liquid diet and ethanol withdrawal was precipitated by replacing ethanol free diet. Ethanol receiving rats in individual groups were decapitated on 21st day of ethanol ingestion and at sixth hour of ethanol withdrawal. Brains were removed and dissected. Five regions of the brain were dissected: the frontal cortex, cerebellum, striatum, hippocampus and hypothalamus. Immunohistochemical NOS staining was performed. The NOS staining intensity in cortex and hypothalamus regions were significantly lower in EWS group than control group. During EWS period, in rats given 2.5 and 10 mg/kg escitalopram, the staining intensity in cortex, striatum and hippocampus were found to be 11.492, 8.519 and 11.234, respectively, and was statistically different than the control group. The hippocampal NOS staining intensity was found to be significantly decreased with 2.5 mg/kg escitalopram, whereas the cortex, striatum and hippocampal staining intensity were increased significantly with 5 mg/kg. In 10 mg/kg escitalopram group, staining properties were not different than those of the control group. Our results suggest that NOS decreases during ethanol withdrawal in cortex and hypothalamus of rat brain and treatment with escitalopram reverses the enzyme density in cortex but not hypothalamus.

Hyperglycemia is a predictor of prognosis in traumatic brain injury: Tertiary intensive care unit study

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 Students 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.

ED50 and ED95 of intrathecal isobaric levobupivacaine coadministered with fentanyl for transurethral resections: randomized, double-blind trial.

BACKGROUND Levobupivacaine use is progressively increased for intrathecal anesthesia in transurethral resections. The aim was to determine ED(50) and ED(95) of intrathecal isobaric levobupivacaine by addition of 25 mcg 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 14 mg in equal volumes with 25 mcg intrathecal fentanyl addition. Sensorial block level was determined by pinprick and motor block by Bromage scale. RESULTS Mean onset time of sensorial block in 6 mg group was significantly longer than that of sensorial block in 10 mg, 12 mg and 14 mg groups (p<0.01), 8 mg was longer than 12 mg and 14 mg (p<0.01), and 10 mg onset time of sensorial block was significantly longer than 12 mg and 14 mg (p<0.01). Mean onset time of T10 sensory level in 6 mg group was significantly longer than mean onset time of T10 sensory level in 10 mg, 12 mg and 14 mg (p<0.01), the mean onset time of T10 sensory level in 8 mg group was also significantly longer than that of 12 mg, 14 mg groups (p<0.01). ED(50) and ED(95) of levobupivacaine coadministered with 25 mcg fentanyl were 7.32 mg and 10.88 mg, 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.

Comparison of intrathecal hyperbaric bupivacaine and levobupivacaine with fentanyl for caesarean section

Background: Use of levobupivacaine as pure S(-) enantiomer of bupivacaine is progressively increased due to lower cardiotoxicity and neurotoxicity and shorter motor block duration.. The aim was to compare the efficacy of lower dose local anesthetics use together with higher opioid dose to decrease side effects of drugs. We compared sensorial, motor block levels and side effects of equal doses of hyperbaric bupivacaine and levobupivacaine with intrathecal fentanyl addition in elective caesarean cases.