The effect of centrally injected Gly-Gln after acute and chronic morphine administration on dopamin and DOPAC output in Nucleus accumbens

Bu çalışmada akut ve kronik olarak morfin uygulanması sonrası nukleus akkumbens'te (NAk) dopamin ve dihidroksifenilasetik asit (DOPAC) salınımı üzerine Glycyl-L-Glutamin'in (Gly-Gln) etkisi araştırıldı.Deneylerde 300-350 g ağırlığında Sprague-Dawley erkek sıçanlar kullanıldı. Morfin hidroklorür intraperitoneal (i.p.), Gly-Gln intraserebroventriküler (i.s.v.) yolla verildi. NAk'e yerleştirilen mikrodiyaliz probundan toplanan örneklerde Yüksek Basınçlı Sıvı Kromatografisi (High Pressure Liquid Cromatography, HPLC) kullanılarak dopamin ve DOPAC düzeyleri ölçüldü.Gly-Gln (1, 3, 30 ve 100 nmol/5?l; i.s.v.) tek doz morfin (2,5 mg/kg; i.p.) verilmesi sonrası görülen dopamin artışını doz ve zamana bağlı olarak anlamlı bir şekilde inhibe etti. Benzer şekilde kronik morfin verilmesi (6 gün sabah ve akşam 10 mg/kg; i.p.) ile görülen dopamin çıkışı da Gly-L-Gln (100 nmol/5?l; i.s.v.) ile bloke oldu.Bu çalışmadan elde edilen bulgular Gly-Gln'in morfin bağımlılığını önleyici etkisinde NAk'te dopamin salıverilmesini azaltmasının rolü olabileceğini ortaya koymaktadır. Kronik dönemde de benzer etkinin gözlenmesi Gly-Gln'in terapötik potansiyele sahip olabileceği görüşünü desteklemektedir.In this study the effect of Glycyl-Glutamine (Gly-Gln) on dopamine and DOPAC (3,4-Dihydroxy-Phenylacetic Acid) release in nucleus accumbens (NAc.) after acute and chronic morphine administration was investigated.Sprague-Dawley male, 300-350 g weight rats were used in the experiments. Morphine hydroclorur was injected intraperitoneally (i.p.), Gly-Gln was administered intracerebroventricularlly (i.c.v.). NAc dialyisate Dopamin and DOPAC levels were evaluated by using High Pressure Liquid Chromatography (HPLC).Gly-Gln (1, 3, 30 ve 100 nmol/5?l; i.c.v.) significantly inhibited the dopamine increase caused by single dose morphine (2,5 mg/kg) administration in time and dose dependent manner. Gly-Gln (100 nmol/5?l; i.c.v.) also blocked dopamine increase seen after chronic morphine (6 days , given twice daily 10 mg/kg , i.p.) administration singificantly.The findings obtained from this study showed that Gly-Gln?s preventing role in morphine dependence is related to its dopamin inhibiting effect in n.acc. This blockage was seen also in chronic morphine administration which strengthens the possibility of Gly-Gln as therapeutic agent

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.lntracerebroventricular (i.c.v.) 0.5,1.0 and 2.0 mu mol 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 mu mol) and cytidine (1.0 mu mol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 mu g) and mecamylamine (50 mu g) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 mu mol 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 close- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDPcholine 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. (C) 2015 Elsevier B.V. All rights reserved

Suboptimal use of non-vitamin K antagonist oral anticoagulants: Results from the RAMSES study

WOS: 000384041400052PubMed ID: 27583892This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians' adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study).RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression.Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance 50mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of 3.The suboptimal use of NOACs is common because of physicians' poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients

Guideline-adherent therapy for stroke prevention in atrial fibrillation in different health care settings: Results from ramses study

Objective No studies have been conducted in Turkey to compare the quality of stroke prevention therapies provided in different healthcare settings in patients with atrial fibrillation (AF). Therefore, we aimed to evaluate possible differences between secondary (SH) and tertiary hospital (TH) settings in the effectiveness of implementing AF treatment strategies. Methods Baseline characteristics of 6273 patients with non-valvular AF enrolled in the RAMSES (ReAl-life Multicentre Survey Evaluating Stroke Prevention Strategies in Turkey) study were compared. Results Of the study population, 3312 (52.8%) patients were treated in THs and 2961 (47.2%) patients were treated in SHs. Patients treated in the SH setting were older (70.8 ± 9.8 vs. 68.7 ± 11.4 years, p &lt; 0.001), had a lower socioeconomic status, had a higher CHA2DS2VASc and HASBLED scores (3.4 ± 1.4 vs. 3.1 ± 1.7, p &lt; 0.001 and 1.7 ± 1.0 vs. 1.6 ± 1.1, p &lt; 0.001 respectively), and had more comorbidities than patients treated in THs. Inappropriate oral anticoagulant use was more prevalent in SHs than THs (31.4% vs. 25.6%, p &lt; 0.001). When over- and undertreatment rates were compared among hospital types, overtreatment was more prevalent in THs (7.6% vs. 0.9%, p &lt; 0.001) while undertreatment was more common in SHs (30.5% vs. 17.9%, p &lt; 0.001). Conclusion This study demonstrates the marked disparity between patient groups with AF presenting at SHs and THs. The use of guideline-recommended therapy is not adequate in either type of centre, overtreatment was more prevalent in THs and undertreatment was more prevalent in SHs