1 The objective of this study was to investigate the ability of aminoguanidine, methylguanidine and guanidine to inhibit free radicals or metabolites generated by either stimulated human leucocytes or cellfree systems using luminol-enhanced chemiluminescence (CL). 2 Aminoguanidine (0.1 mM ± 10 mM), methylguanidine (10 mM ± 10 mM) and guanidine (10 mM ± 10 mM) produced concentration-dependent inhibition (96+0.1%, n=7, 59+1.3%, n=6, and 62+3%, n=6, P50.05 at 10 mM, respectively) in FMLP-stimulated leucocytes CL. 3 In cell-free experiments, hydrogen peroxide (H 2 O 2 ), hypochlorous acid (HOCl), hydroxyl radical and peroxynitrite-induced CL responses were initiated by hydrogen peroxide (3.5 mM), NaOCl (50 mM), FeSO 4 (40 nM) and peroxynitrite (20 nM), respectively. Aminoguanidine, methylguanidine and guanidine produced concentration-dependent inhibition in H 2 O 2 -(69+0.7%, n=7, 26+1%, n=6, and 15+0.5%, n=6, at 1 mM, respectively) and HOCl-(84+0.3%, n=6, 50+1%, n=6, and 29+1%, n=7, at 1 mM, respectively) induced luminol CL. Peroxynitrite-induced CL was markedly attenuated in a concentrationdependent manner by aminoguanidine (99+0.1%, n=6, at 10 mM), methylguanidine (5+0.2%, n=6, at 10 mM) and guanidine (27+0.4%, n=7, at 10 mM). However, inhibition with aminoguanidine was found to be more marked than with methylguanidine and guanidine. Aminoguanidine (95+0.5%, n=6, at 1 mM) and methylguanidine (25+1%, n=6, at 1 mM), but not guanidine (2+1%, n=6, at 1 mM), signi®cantly decreased ferrous iron-induced CL. 4 Collectively, these data suggest that aminoguanidine and a high concentration (50.1 mM) of methylguanidine have direct scavenging activities against H 2 O 2 , HOCl, hydroxyl radical and peroxynitrite. Guanidine, at a high concentration (50.1 mM), scavenges H 2 O 2 , HOCl and peroxynitrite, but not the hydroxyl radical. These direct scavenging properties may contribute to inhibitory eects of these compounds on human leucocyte CL.

Glioblastoma multiforme (GBM) is one of the most lethal forms of cancer in humans, with a median survival of 10 to 12 months. Glioblastoma is highly malignant since the cells are supported by a great number of blood vessels. Although new treatments have been developed by increasing knowledge of molecular nature of the disease, surgical operation remains the standard of care. The TRP (transient receptor potential) superfamily consists of cation-selective channels that have roles in sensory physiology such as thermo- and osmosensation and in several complex diseases such as cancer, cardiovascular, and neuronal diseases. The aim of this study was to investigate the expression levels of TRP channel genes in patients with glioblastoma multiforme and to evaluate the relationship between TRP gene expressions and survival of the patients. Thirty-three patients diagnosed with glioblastoma were enrolled to the study. The expression levels of 21 TRP genes were quantified by using qRT-PCR with dynamic array 48 × 48 chip (BioMark HD System, Fluidigm, South San Francisco, CA, USA). TRPC1, TRPC6, TRPM2, TRPM3, TRPM7, TRPM8, TRPV1, and TRPV2 were found significantly higher in glioblastoma patients. Moreover, there was a significant relationship between the overexpression of TRP genes and the survival of the patients. These results demonstrate for the first time that TRP channels contribute to the progression and survival of the glioblastoma patients.

1 The aim of this study was to investigate the involvement of peroxynitrite, reactive metabolite originating from nitric oxide and superoxide, in preconditioning of the ischaemic myocardium in rat isolated hearts. 2 Isolated hearts perfused with Krebs-Henseleit solution were preconditioned either by 3 min of coronary artery occlusion (CAO) or by peroxynitrite administration at three dierent concentrations (0.1, 1, 10 mM) for 3 min, followed by 10 min reperfusion and 30 min of CAO. Peroxynitrite, at 1 mM concentration, decreased the incidence of VT from 100% (n=14) to 62% (n=13) and abolished the occurrence of VF (50% in the control group). 3 N-2-mercaptopropionylglycine (MPG, 1 mM ± 10 mM) produced a concentration-dependent inhibition of peroxynitrite signals in luminol chemiluminescence and 67+1% inhibition was observed at 100 mM (n=7). MPG (at 300 mM, n=7) added to the perfusate 10 min prior to ischaemic preconditioning or peroxynitrite infusion and maintained until CAO, signi®cantly reversed the bene®cial eects of the ischaemic and peroxynitrite-treated groups. MPG administration in the peroxynitrite-treated group increased the incidence of VT from 62% (n=13) to 100% (n=10) and total VF from 0% (n=0) to 67% (n=10). Similarly, MPG elevated the incidence of VT from 50% (n=10) to 100% (n=8) in the ischaemic preconditioned group. On its own, MPG did not aect the severity of cardiac arrhythmias. 4 These results suggest that endogenously produced peroxynitrite plays a signi®cant role in the antiarrhythmic eect of ischaemic preconditioning in the rat isolated hearts.

These results suggest that dexmedetomidine provides analgesia, adequate sedation and surgical comfort without adverse effects for patients undergoing functional endoscopic sinus surgery under local anaesthesia.

The aim of the study was to elucidate the mechanism of the contraction produced by hypoxia in human intrapulmonary artery rings. Hypoxia (5 mm Hg) produced a contraction that was greater when the artery rings were precontracted (with endothelin-1) than when recorded under optimal resting force. The contraction was similar in small-diameter (0.38 to 0.68 mm) and in large-diameter (2.2 to 4.5 mm) artery rings under resting force. Removal of the endothelium markedly reduced or abolished the hypoxic contraction in precontracted artery rings (large diameter, 26 +/- 9 to -7 +/- 4 g cm-2) or under optimal resting force. Hypoxia markedly reduced or abolished the acetylcholine-induced relaxation in precontracted artery rings without affecting relaxation produced by sodium nitroprusside. Flurbiprofen caused a slight contraction itself (large diameter, 10 +/- 3 g cm-2) and significantly inhibited the contraction produced by hypoxia both under resting force (8 +/- 2 to 2 +/- 1 g cm-2) and in precontracted artery rings (18 +/- 2 to 1 +/- 1 g cm-2). Verapamil had no significant effect on the hypoxic contraction either under resting force or when precontracted. It is concluded that hypoxic contraction of human pulmonary artery rings depends on the presence of endothelium and is partly due to inhibition of a vasodilator cyclooxygenase product.