Purpose: Aging increases the prevalence of diseases. The elderly population is consequently often exposed to complex medication regimens. Increased drug use is one of the main reasons for drug-related problems (DRPs). The primary objective of this study was to define and classify DRPs, pharmacist interventions, and frequently prescribed medications in relation to possible DRPs in patients admitted to the geriatric ward of a teaching hospital in Turkey. Patients and methods: Pharmacist medication review reports for 200 orders of 91 patients (mean age: 80.33±0.46) were analyzed retrospectively. Results: A total of 1,632 medications were assessed and 329 interventions were proposed for possible DRPs in 156 orders. A total of 87.5% of the patients used five or more drugs (mean: 8.17±0.23). The number of DRPs per order was higher when polypharmacy was present (1.04±0.15 vs 1.66±0.11, P<0.05). In 71.31% of the cases, adverse drug events were recognized as the problem. The principal cause of possible DRPs was determined as drug interactions (40.12%). Only 22 potentially inappropriate medications were prescribed. The most common interventions included monitoring drug therapy (31.0%), stopping the drug (20.06%), and changing dosage (13.98%). The acceptance rate of pharmacist interventions by treating geriatrician was 85.41%. The most frequently prescribed drugs were for the nervous system, alimentary tract and metabolism, and cardiovascular system (n=358, 314, and 304, respectively). The pharmaceutical forms of 23 drugs were deemed inappropriate by pharmacists. Conclusion: Clinical pharmacy services are still not properly implemented in Turkey. The study highlights ways in which clinical pharmacy services can be instrumental in a geriatric ward. The high acceptance rates of pharmacist recommendations concerning a wide variety of DRPs and different classes of drugs indicate that advanced collaboration among geriatricians and pharmacists is possible in interdisciplinary geriatric assessment teams in Turkey.

Background: Methylglyoxal is a major precursor in the formation of advanced glycation end products and is associated with the pathogenesis of diabetes-related vascular complications. The aim of this study was to evaluate whether methylglyoxal induces endothelial dysfunction and to determine the contributors involved in this process. Methods: Rat thoracic aortic rings were treated for 24 h with 100 μM methylglyoxal by using an organ culture method. A cumulative dose-response curve to acetylcholine was obtained to determine endothelium-dependent relaxation. The protein levels of endothelial nitric oxide synthase (eNOS) and its phosphorylated form at the serine 1177 site [p-eNOS (Ser1177)], heat shock protein 90 (Hsp90), AMP-activated protein kinase α (AMPKα) and its phosphorylated form at the threonine 172 site [p-AMPKα (Thr172)] were evaluated. Superoxide production was determined by lucigenin-chemiluminescence. Results: Treatment with 100 μM methylglyoxal for 24 h decreased acetylcholine-induced vascular relaxation. The levels of eNOS and p-eNOS (Ser1177) were reduced while no effect on Hsp90 was observed. Levels of p-AMPKα (Thr172) were significantly decreased without any change in total AMPKα protein levels. Superoxide level was not affected by methylglyoxal treatment. Conclusions: In rat aortic rings, methylglyoxal determines a reduction in endothelium-dependent relaxation. This effect seems to be mediated via a reduction in p-eNOS (Ser1177) and p-AMPKα (Thr172).

Exposure to mercury has detrimental effects on the cardiovascular system, particularly the vascular endothelium. The present study aimed to investigate the effects of ergothioneine (EGT) on endothelial dysfunction induced by low‑dose mercury chloride (HgCl2). Agonist‑induced contractions and relaxations were evaluated in isolated aortic rings from 3‑month‑old male Wistar rats treated by intra‑muscular injection to caudal hind leg muscle with HgCl2 (first dose, 4.6 µg/kg; subsequent doses, 0.07 µg/kg/day for 15 days) and optionally with EGT (2 µg/kg for 30 days). Reactive oxygen species (ROS) in aortic rings were measured by means of lucigenin‑ and luminol‑enhanced chemiluminescence. The protein level of endothelial nitric oxide synthase was evaluated by ELISA. Blood glutathione (GSH) and catalase levels, lipid peroxidation and total nitrite were measured spectrophotometrically. The results indicated that low‑dose HgCl2 administration impaired acetylcholine (ACh)‑induced relaxation and potentiated phenylephrine‑ and serotonin‑induced contractions in rat aortas. In addition, HgCl2 significantly increased the levels of ROS in the aortic tissue. EGT prevented the loss of ACh‑induced relaxations and the increase in contractile responses. These effects were accompanied by a significant decrease in ROS levels. EGT also improved the ratio of reduced GSH to oxidized GSH and catalase levels with a concomitant decrease in lipid peroxidation. In conclusion, to the best of our knowledge, the present study was the first to report that EGT prevents endothelial dysfunction induced by low‑dose HgCl2 administration. EGT may serve as a therapeutic tool to reduce mercury‑associated cardiovascular complications via improving the antioxidant status.

AMP-activated protein kinase (AMPK) is a regulator of cellular metabolism and is involved in the pathogenesis of several diseases, including type 2 diabetes and cardiovascular diseases. Data showing the effects of AMPK on vasculature are controversial. Therefore, the aim of this study was to determine the impact of prolonged AMPK activation on vascular functions. For this purpose we have examined the role of AMPK in endothelium-dependent and -independent relaxation and vascular contractions. For this, we incubated thoracic aortic rings, from rats, with AMPK activator 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR, 500 μmol/L or 2 mmol/L) in the presence or absence of AMPK inhibitor compound C (10 μmol/L). Next, cumulative dose–response curves to acetylcholine (ACh) (10⁻⁹−10⁻⁴mol/L), nitroglycerine (NG) (10⁻⁹–3 × 10⁻⁵mol/L), and noradrenaline (NA) (10⁻⁹−10⁻⁴mol/L) were obtained. Endothelial nitric oxide synthase (eNOS) protein expression was determined. Our results show that endothelium-dependent relaxation was inhibited after AICAR treatment, and that this effect was reversed by AMPK inhibition. Moreover, AICAR enhanced the contractile response to NA and caused a decrease in eNOS protein expression. In conclusion, prolonged AMPK induction causes endothelial impairment, possibly via increased degradation and (or) reduced expression of eNOS.

Placing a silicone collar around the rabbit carotid artery induces intimal thickening, an early stage in atherosclerosis and restenosis. We investigated whether treatment with oral pranidipine, a new potent, long-lasting dihydropyridine calcium channel blocker (CCB), inhibited collar-induced intimal thickening in addition to the changes in vascular reactivity usually observed in this model. Pranidipine treatment did not inhibit collar-induced intimal thickening. Placing the collar around the carotid artery resulted in the characteristic changes in vascular reactivity, such as increased sensitivity to 5-hydroxytryptamine. Treatment with N^ω-nitro-l-arginine (100 μM) and pranidipine, however, did not affect collar-induced changes in vascular reactivity. From results of this and previous studies, we conclude that pranidipine does not prevent collar-induced intimal thickening or collar-induced changes in vascular reactivity. Not all CCBs prevent collar-induced intimal thickening, suggesting that the effects of these agents are not related to their chemical structure and/or their calcium channel-blocking actions.