Rationale, design and methodology of the RAMSES Study: ReAl-life Multicenter Survey Evaluating Stroke Prevention Strategies.

OBJECTIVE: Atrial fibrillation is the most common arrhythmia and is associated with a five- fold increased risk of thromboembolic events. Vitamin K antagonists (VKAs) have been the mainstay of oral anticoagulant prophylaxis and the data on stroke prevention strategies are limited to VKA era. The purpose of this study is to evaluate the use of VKA, non-Vitamin K antagonist oral anticoagulants (NOAC), and antiplatelet agents in patients with non-valvular atrial fibrillation (NVAF). METHODS: The ReAl-life Multicenter Survey Evaluating Stroke prevention strategies in Turkey (RAMSES) is an observational, multicenter, prospective study of patients with NVAF. The study targeted enrollment of 7835 patients from 68 sites in Turkey. All the data will be collected at one point in time and current clinical practice will be evaluated. (ClinicalTrials.gov number NCT02344901). RESULTS: Baseline characteristics of patients, antithrombotic therapies, transition to NOACs and rate/rhythm control strategies will be evaluated. CONCLUSION: The RAMSES registry will be the largest study in Turkish NVAF patients. The study will provide insights into real-world problems and anticoagulant treatment in patients with NVAF.

Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels.

Patients' experience and perspectives on the rational use of drugs in Turkey: a survey study.

AIM: Physicians' inappropriate prescribing habits affect patients' lives both medically and financially. To avoid these unwanted situations, the World Health Organization defined the rational use of drugs (RUD) in 1985. This study aimed to investigate whether patients were as informed about their diagnosis and medication as anticipated and their knowledge about the RUD in general. METHODS: A questionnaire was given to 260 patients being treated at the Kartal Training and Research Hospital between February and March 2012. RESULTS: Most of the patients declared that they were not informed enough about their diagnosis and not all of the physicians evaluated their therapies. These undesirable conditions were due to high daily examined patient numbers. A total of 68.6% of patients stated that time allotted per patient was 0-10 minutes, 33.1% found the information given sufficient, and 11.3% were told to repeat back narratives about their treatments. Instructions and warnings given by physicians about prescribed drugs did not fully meet the RUD criteria. The majority of referred patients were willing to be educated about the subject. CONCLUSION: These results showed that heavy patient load seriously affects the RUD process. Improvement of the current health system should be given serious consideration. After sufficient arrangements have been made in this field, patients will be able to be informed properly about medicines prescribed by their physicians. Also, public education programs will be helpful to raise awareness of the subject on a larger scale.

Glycyl-glutamine (beta-endorphin(30-31)) inhibits morphine-induced dopamine efflux in the nucleus accumbens.

Glycyl-glutamine (Gly-Gln) is an endogenous dipeptide that is synthesized from beta-endorphin post-translationally. Previously, we showed that Gly-Gln prevents acquisition of morphine-conditioned place preference, a behavioral test of morphine reward, but does not interfere with morphine analgesia. In this study, we tested the hypothesis that Gly-Gln inhibits morphine reward by blocking morphine-induced dopamine efflux in the nucleus accumbens (NAc). Extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were sampled by microdialysis and analyzed by high-performance liquid chromatography with electrochemical detection. Guide cannulas were implanted in the right NAc and left lateral ventricle of male Sprague-Dawley rats stereotaxically. Approximately 24 h later, a microdialysis probe was inserted into the NAc and perfused at 1 microl/min. Gly-Gln (1, 3, 30, or 100 nmol/5 microl) or saline was administered intracerebroventricularly, morphine (2.5 mg/kg) was injected intraperitoneally (i.p.) 2 min later, and extracellular dopamine and DOPAC were sampled at 20-min intervals. Morphine administration increased extracellular dopamine concentrations by approximately 600% within 40 min. Gly-Gln pretreatment inhibited the rise in extracellular dopamine in a dose-related manner; the lowest significantly inhibitory dose was 1 nmol. Gly-Gln also inhibited the morphine-induced rise in extracellular DOPAC concentrations but did not affect extracellular dopamine or DOPAC in control animals. Gly-Gln (100 nmol/5 microl) prevented morphine-induced dopamine efflux in rats treated with morphine chronically (10 mg/kg, i.p. twice daily for 6 days), although it did not affect DOPAC concentrations significantly. These data support the hypothesis that Gly-Gln abolishes the rewarding effect of morphine by inhibiting the ability of morphine to stimulate dopamine release in the NAc.