Yeşim HAMURTEKİN, Ammar NOUILATI, Cansu DEMİRBATIR, Emre HAMURTEKİN* Asetaminofen yaygın kullanılan analjezik ve antipiretik bir ajandır. Reçetesiz verilebilen formülasyonlarının da mevcudiyeti sık kullanımını artırmıştır. Günümüze kadar asetaminofenin analjezik etki mekanizmasını inceleyen bir çok çalışma bulunmaktadır. Santral sinir sisteminde siklooksijenaz yolağını inhibe etmesinin yanında, opioiderjik, kannabinoiderjik, dopaminerjik, kolinerjik ve nitrerjik sistemler kadar, bulbospinal serotonerjik yolaklar gibi analjezik etkili inen inhibitör yolakların da asetaminofenin analjezik etkisinde katkısı olan olası mekanizmalar olduğu önerilmiştir. Bu derlemede santral serotonerjik sistem ve santral sinir sistemindeki serotonerjik reseptör alt tiplerinin parasetamolün analjezik etkisine katkısını ortaya koyan verileri bir araya getirmeyi amaçladık. Bunu yaparken, esas olarak son on yılda yapılmış çalışmalara odaklandık ve önceki verilerle son eklenenler arasında bir bağlantı kurmaya çalıştık. Serotonerjik sistemin katkısına ek olarak, aynı zamanda son on yıldaki yeni bulgularla asetaminofenin ağrı kesici etkisinde nitrik oksidin rolünü de derledik. Anahtar kelimeler: Asetaminofen, serotonin, ağrı, nitrik oksit Acetaminophen is a widely used analgesic and antipyretic agent. It is also available in over the counter formulations, which has increased its wide use. There have been many studies to date that have aimed to evaluate the mechanism of the analgesic action of acetaminophen. Additional to the inhibition of the cyclooxygenase pathway in the central nervous system, the involvement of opioidergic, cannabinoidergic, dopaminergic, cholinergic, and nitrergic systems as well as the contribution of descending pain inhibitory systems like the bulbospinal serotonergic pathway has been proposed as possible mechanisms of the analgesic action of acetaminophen. In this review, we aimed to collect the data from studies revealing the contribution of the central serotonergic system and the role of central nervous system-located serotonergic receptor subtypes in the analgesic effect of acetaminophen. While doing this, we mainly focused on the research that has been performed in the last ten years and tried to link the previous data with the lately added results. In addition to serotonergic system involvement, we also reviewed the role of nitric oxide in the analgesic action of acetaminophen, especially with the new findings reported over the last decade.

The aim of this study is to assess the results of inspections in the last three years of drug abuse testing in medical laboratories according to the latest regulations in Turkey. The on-site inspections of medical laboratories for drugs abuse testing performed in Alcohol and Drug Addiction Treatment Centers during 2014-2016 are described, and laboratory processes and performance evaluated. The performance of 35 laboratories in 2014, 62 laboratories in 2015, and 94 laboratories in 2016 were scored as the sum of the scores for all answers on the inspection form. An inspected laboratory was considered to have an unconformity if the total score was less than 2/3 of maximum score. The total scores of inspections and the number of laboratories with between years were compared using one-way analysis of variance and slope Chi-square for trend test, respectively. Total scores increased statistically significantly from 35.9 ± 16.2 in 2014, to 43.5 ± 16.3 in 2015 and 49.1 ± 1.3 in 2016 (p < 0.001). The laboratories with unconformities decreased statistically significantly from 57% in 2014 to 37% in 2015 and 22% in 2016 (p < 0.001). The published legislation and the inspections contributed to national standardization and improved quality of service in medical laboratories for drug abuse testing.

Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.