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Rationale, aims, and objective: There is limited information about the comparative effectiveness of the START/STOPP (Screening Tool of Older Person's Prescriptions/Screening Tool to Alert doctors to Right Treatment) criteria and the Ghent Older People's Prescriptions community Pharmacy Screening tool (GheOP 3 S tool) for the screening of potentially inappropriate prescribing (PIP) in the geriatric population. Considering this, the aim of this study was to compare the ability of the START/STOPP criteria and GheOP 3 S tool to identify the PIP and potential prescribing omissions (PPOs) among elderly patients visiting their primary care physician.Methods: This is a retrospective observational study where a total of 422 subjects were included. The Charlson Co-morbidity Index (CCI) and the Medicines Comorbidity Index (MCI) for older people were used to determine the co-morbidity status. The user's diagnosis and medications prescribed were analysed with the START/STOPP criteria and GheOP 3 S tool. The Wilcoxon signed rank test was used to compare these criteria. The statistical relationship between the occurrence of PIP and users' age, the number of medication prescribed, the number of diagnoses, CCI, and MCI was determined with one-tailed bivariate correlation. Results:The START/STOPP criteria detected 843 PIPs and 1067 PPOs, while the GheOP 3 S tool detected 936 PIPs and 202 PPOs. The GheOP 3 S tool detected significantly more PIPs than did the STOPP criteria (P = 0.003). A significantly higher number of PPOs were detected with the START criterion (P < 0.0001). The results obtained with the START/STOPP criteria positively correlated with mentioned variables. Oppositely, there is a negative correlation between the results obtained with the GheOP 3 S tool and age. Still, the positive correlation could be found with the rest of the variables. Conclusion:The results of this study indicate that both tested tools demonstrated efficiency to detect PIPs and PPOs. The GheOP 3 S tool detected significantly more PIPs than did the STOPP criteria. On the other hand, the START criteria performed much better for the screening of PPOs.

The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO) synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells' count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

Gentamicin, belonging to the aminoglycosides, possesses the greatest nephrotoxic effect of all other antibiotics from this group. On the other hand, pioglitazone, which represents peroxisome proliferator-activated receptor γ (PPARγ) agonist recently showed antiinflamatory, antioxidative effects, amelioration of endothelial dysfunction etc. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. These effects were observed by following values of biochemical (serum urea and creatinine) parametars, total histological kidney score, urine level of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as well as parametars of oxidative stress (malondialdehyde, superoxide dismutase, catalase, total oxidant status, total antioxidant status, oxidative stress index and advanced oxidation protein products). It seems that pioglitazone protects the injured rat kidney in a U-shaped manner. Medium dose of pioglitazone (1 mg/kg, i.p.) was protective regarding biochemical (serum urea and creatinine), total histological score and the values of kidney injury molecule-1 (KIM-1) (P < 0.05 vs. control group, i.e. rats injected with gentamicin only). This finding could be of great importance for the wider use of aminoglycosides, with therapy that would reduce the occurrence of serious adverse effects, such as nephrotoxicity and acute renal failure.

The amphipathic peptide duramycin is in clinical development for the treatment of cystic fibrosis. It is deposited in cellular membranes where it binds to phosphatidylethanolamine. Duramycin may thereby change the biophysical membrane properties and perturb the function of ion channels. If so, in heart tissue, its application carries the risk to elicit cardiac arrhythmias. In fact, premature ventricular complexes were observed in the electrocardiogram during toxicological testing in dogs. To study the arrhythmogenic potential of duramycin, we investigated its effects on currents through voltage-gated hERG potassium, sodium, and calcium channels in native cells, and using a heterologous expression system, by means of the whole-cell patch clamp technique; duramycin bath concentrations between 1 nM and 0.1 microM did not generate any effects on these currents. Concentrations >or=0.3 microM, however, reduced the amplitudes of all investigated currents. Moreover, sodium current fast inactivation kinetics was slowed in the presence of duramycin. A further rise in duramycin bath concentration (>or=3.3 microM) induced a leak current consistent with pore formation. The reported effects of duramycin on ion channel function are likely to arise from a change in the biophysical properties of the membrane rather than from a specific interaction of the peptide with ion channel proteins. Under therapeutic conditions (i.e., administration via inhalation), duramycin plasma concentrations are below 0.5 nM. Thus, upon inhalation, duramycin has a large safety margin and is highly unlikely to elicit arrhythmias.

Abstract:The present experiments were undertaken in order to examine the effect of adenosine in isolated rat aorta, to investigate the possible role of intact endothelium and endothelial relaxing factors in this action and to determine which population of adenosine receptors is involved in rat aorta response to adenosine. Adenosine (0.1-300 mM) produced concentration-dependent (intact rings: pD 2 Ω4.39∫0.09) and endothelium-independent (denuded rings: pD 2 Ω4.52∫0.12) relaxation of isolated rat aorta. In the presence of high concentration of K π (100 mM) adenosine-evoked relaxation was significantly reduced (maximal relaxation in denuded rings: control -92.1∫9.8 versus K π -54.4∫5.0). Similar results were obtained after incubation of ouabain (100 mM) or glibenclamide (1 mM). In K π -free solution, K π (1-10 mM)-induced rat aorta relaxant response was significantly inhibited by ouabain (100 mM). Application of indomethacin (10 mM), N G -nitro-L-arginine (10 mM) or tetraethylammonium (500 mM) did not alter the adenosine-elicited effect in rat aorta. 8-(3-Chlorostyril)-caffeine (0.3-3 mM), a selective A 2A -receptor antagonist, significantly reduced adenosine-induced relaxation of rat aorta in a concentration-dependent manner (pK B Ω6.57). Conversely, 1,3-dipropyl-8-cyclopentylxanthine (10 nM), an A 1 -receptor antagonist, did not affect adenosine-evoked dilatation. These results indicate that in isolated rat aorta, adenosine produces endothelium-independent relaxation, which is most probably dependent upon activation of smooth muscle Na π /K π -ATPase, and opening of ATP-sensitive K π channels, to a smaller extent. According to receptor analysis, vasorelaxant action of adenosine in rat aorta is partly induced by activation of smooth muscle adenosine A 2A receptors.

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