Cetin Hakan Karadag

Combined systemic administration of morphine and magnesium sulfate attenuates pain-related behavior in mononeuropathic rats

The response to opioids is reduced in neuropathic pain states. We examined the effect of the combination of morphine (0.1 mg/kg) and magnesium sulfate (125 mg/kg) on behavioral signs of neuropathic pain in spinal nerve ligated rats. Administered alone, neither drug produced any effect, but the combination exerted a significant anti-allodynic effect, which was partially reversed by naloxone. These results suggest that combining low doses of magnesium sulfate with opiates might be an alternative in treating neuropathic pain, with reduced risk of side effects.

Involvement of NMDA receptors and nitric oxide in the thermoregulatory effect of morphine in mice.

Summary. Morphine has long been known to have potent effects on body temperature. It has been suggested that both N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO) pathway are involved in thermoregulation and also known to play important roles in some of morphine effects. The aim of this study was therefore to investigate the contribution of NMDA receptors and NO to the thermoregulatory effect of morphine. Morphine produced a hypothermic effect, especially at the dose of 10 mg/kg. Ketamine (5–40 mg/kg, i.p.) and NG-nitro-L-arginine-methyl ester (L-NAME, 1–100 mg/kg, i.p.) also produced hypothermic effects with their higher doses. At doses which themselves produced no effect on colonic temperature in mice, both ketamine (10 mg/kg, i.p.) and L-NAME (10 mg/kg, i.p.) enhanced the hypothermic effect of morphine (10 mg/kg, i.p.). These results further support the relationship between NO and NMDA receptors and suggest a possible role of NMDA-NO pathway in the thermoregulatory effect of morphine.

The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats

OBJECTIVE The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. MATERIAL AND METHODS Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. RESULTS 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. CONCLUSION Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.

Evaluation of Iloprost to Prevent Vasospasm in Coronary Artery Bypass Grafts

This study assessed the efficacy of iloprost in relieving vasospasm in coronary artery bypass grafts. Radial artery (RA), left internal thoracic artery (LITA) and saphenous vein (SV) grafts were taken from 20 patients (13 men and seven women, mean age 63.8 years [range 48 − 74 years]) scheduled to undergo coronary artery bypass grafting. Ten 3 mm vascular rings were cut from each graft and kept under tension for at least 60 min. They were kept alive with 37°C oxygenated Krebs solution. Smooth muscle contraction was achieved with phenylephrine before iloprost was administered every 2 min, starting at a concentration of 10−9 mol/l and increasing in logarithmic increments to a concentration of 10−5 mol/l. The vasodilation response to iloprost started in all samples at a concentration of 10−9 mol/l and increased with each incremental increase in iloprost concentration up to 10−5 mol/l. These data suggest that local administration of iloprost has a role in relieving graft vasospasm during harvesting and preparation for coronary artery bypass grafting.

Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice

We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip) to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20) produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.

Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice

Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing μ‐opioid receptor agonism and noradrenaline re‐uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re‐uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212‐2 and the selective noradrenaline re‐uptake inhibitor maprotiline exert anti‐allodynic synergy on nerve‐injured neuropathic mice.

Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids

Background For centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common. Objective The goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2. Material and methods Scratching behaviour was induced by intradermal injection of serotonin (50 µg/50 µl/mouse) to Balb/c mice. The neurotoxins 5,7-dihydroxytryptamine (5,7-DHT, 50 μg/mouse) and 6-hydroxydopamine (6-OHDA, 20 μg/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. WIN 55,212-2 (1, 3, 10 mg/kg, i.p.) dose-dependently attenuated serotonin-induced scratches. Neurotoxic destruction of neither the serotonergic nor the noradrenergic systems by 5,7-DHT and 6-OHDA, respectively, had any effect on the antipruritic action of WIN 55,212-2. Conclusion Our findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.

Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice

Glutamate is believed to be the predominant excitatory neurotransmitter in the networks responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses serotonin-induced itch-related behavior (similarly to the effect of this agent on pain transmission) in mice. Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam antibiotics looks promising for the treatment of chronic itch.

Announcing the New Website of Balkan Medical Journal

At the end of the last year, we, editorial team, decided to redesign our website to better serve our readers, reviewers and authors. After much hard work, we are excited to officially announce the new and improved Balkan Medical Journal website. You can now reach us at http://balkanmedicaljournal.org/ We thought that it was important to renew the website to reach a wider audience. So, we wanted to have good, clear, easy-tofollow navigation throughout our website. The new website will remain both open access and free of article processing charges. We hope that the website will respond better to our readers’ needs and interests. Key features of the new website include: • Drop down menus to make easier to navigate and improve content layout and design, • Pre-submission inquiry to allow author to have quick feedback from Balkan Medical Journal’s Editors regarding the suitability of a manuscript for the journal, • Image corner which is created from clinical images published in the latest issues for teaching and training purposes, • News section to stay up-to-date on the latest with health news and health science, • Articles section which is composed of selected publications from current issue, • Email alert feature to keep you up-to-date with content of the journal, • We provide you with necessary information about citing in How to Cite, • Advanced Search gives you opportunity to find what you seek more easily, • Select articles you want and make the site to show them with View Selected Articles, • You can share your favorite articles with your colleagues on social media with Share feature. We would like to thank our publisher, Galenos Publishing House, for their tremendous support and effort. For any questions, suggestions, feedback or comments, please contact us via E-mail.

Dopaminin Koroner Arter Bypass Cerrahisi Operasyonlar×nda Kullan×lan únternal Torasik Arter Grefti Üzerine ún Vitro Etkileri

Amac: Bu cal×uman×n amac× dopaminin internal torasik arter (uTA) grefti uzerine etkilerini, invitro araut×rmakt×r. Gerec ve Yontemler: Aral×k 2003- Haziran 2005 tarihleri aras×nda kliniuimizde koroner arter bypass greft (CABG) operasyonu olan toplam 32 hasta (2’si kad×n 30’u erkek, ortalama yau; 59.256±8,.34, 37-75 yaular× aras×) cal×umaya al×nd×. un vitro organ banyosunda hastalar×n ITA’lar×ndan arta kalan parcac×klar uzerinde dopaminin oluuturduuu kas×c× ve gevuetici yan×tlar isometrik olarak kaydedildi. Bulgular: Dopamin 10-9 M-10-7 M konsantrasyon aral×u×nda fenilefrinle onceden kast×r×lm×u ITA’da hafif bir gevueme yan×t×, sonras×nda artan konsantrasyonlar×nda (>10-7 M) kas×lma yan×t× gercekleutirdiui gozlendi. Dopaminin gevuetici etkisinin k×smen L-NAME (nitrik oksit sentaz inhibitoru, 10-6 M), propranolol (10-6 M) ve cis-њ-flupentiksol (dopaminerjik reseptor antagonisti, 10-6 M) ile k×smen azald×u× fakat metoklopramidin (D2-dopaminerjik reseptor antagonisti) dopaminin kaynakl× gevuemeye etki yapmad×u× gozlendi. Dopaminin ITA’daki kas×c× etkisi k×smen fentolamin, prazosin ve yohimbin ile antagonize edildiui gozlendi. Sonuc: Sonuc olarak dopamin duuuk konsantrasyonlarda ITA’da vazodilatasyon yan×t×n× oluutururken daha yuksek konsantrasyonlarda ITA’da vasokonstriksiyon yan×t×n× oluuturmaktad×r. ћ-adrenerjik ve nitrik oksit arac×l× mekanizma (D1-dopaminerjik reseptor yoluyla) dopaminin duuuk konsantrasyonlar×nda ITA’da oluuturduuu gevuetici etkide rol alabilir. Dopaminin yuksek konsantrasyonlardaki ITA’da oluuturduuu kas×c× etki њ1- ve њ2-adrenerjik reseptorlerin aktivasyonu ile oluuturulmaktad×r.