Life sciences
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The relative contributions of cardiomyocyte sarcolemmal ATP-sensitive K(+) (K(ATP)) and mitochondrial K(ATP) channels in the cardioprotection and antiarrhythmic activity induced by K(ATP) channel openers remain obscure, though the mitochondrial K(ATP) channels have been proposed to be involved as a subcellular mediator in cardioprotection afforded by ischemic preconditioning. In the present study, we sought to investigate the effects of administration of ATP-sensitive K(+) channel (K(ATP)) openers (nicorandil and minoxidil), a specific mitochondrial K(ATP) channel blocker (5-hydroxydecanoate (5-HD)) and a specific sarcolemmal K(ATP) channel blocker (HMR 1883; (1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methylthiourea) prior to coronary occlusion as well as prior to post-ischemic reperfusion on survival rate, ischemia-induced and reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. The thorax was opened in the left 4th intercostal space and after pericardiotomy the heart was exposed. ⋯ In the present study, higher levels of malondialdehyde (MDA) and lower levels of reduced glutathione (GSH) and superoxide dismutase (SOD) in necrotic zone of myocardium in all the 16 subgroups in Group II suggest little anti-free radical property of nicorandil and minoxidil. We conclude that intervention by intravenous administration of nicorandil and minoxidil (through the selective activation of mitochondrial K(ATP) channels) increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to coronary occlusion. The cardiomyocyte mitochondrial K(ATP) channel may be a pharmacologically modulable target of cardioprotection and antiarrhythmic activity.
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Comparative Study
Neuromechanical effects of pyrethroids, allethrin, cyhalothrin and deltamethrin on the cholinergic processes in rat brain.
Our previous microdialysis study of freely moving rats demonstrated that 3 pyrethroids, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II) differentially modulate acetylcholine (ACh) release in the hippocampus. To better understand the mechanisms of their modulatory effects and also other effects on the cholinergic system in the brain, the activities of ACh hydrolyzing enzyme acetylcholinesterase (AChE), ACh synthesizing enzyme choline acetyltransferase (ChAT) and ACh synthesizing rate-limiting step, high-affinity choline uptake (HACU) were examined in the present study. The pyrethroids studied had no effect on AChE activity in the cortex, hippocampus and striatum. ⋯ Allethrin (60 mg/kg) and cyhalothrin (20 and 60 mg/kg) decreased while deltamethrin (60 mg/kg) increased the Vmax for HACU. In vitro study showed that at higher concentrations (> or = 10(-) (6) M) allethrin and cyhalothrin reduced the hippocampal HACU but deltamethrin increased it. These results suggest that mechanisms of ACh synthesis are involved in the modulatory effects of the pyrethroids on ACh release and other cholinergic activities.
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Due to the increasing importance of nitrosative stress in pathology and the efficacy displayed by flavonoids in cancelling the effects of peroxynitrite, we decided to conduct a comparative study of three commonly used beverages with the highest polyphenol contents and proven antioxidant properties: mate (Ilex paraguariensis); green tea (Camelia sinensis) extracts and white and red wines of the main varietals. We directly evaluated and compared the extracts and wines as protein nitration inhibitors using 3-nitrotyrosine as a biomarker, we studied the extracts as protectors from OONO-induced cytotoxicity in two mammalian cell lines. Both green tea and mate extracts have a high polyphenol content, in the case of Ip, its higher concentration and higher free radical quenching activity on the DPPH assay may be mainly due to the sui generis extraction procedure. ⋯ When we studied peroxynitrite-induced cytotoxicity in murine RAW 264.7 macrophages and 31EG4 mammary cells., we found a potent, dose-dependent protective effect that was Ilex paraguariensis > red wines > green tea. Taken together, our results indicate that when the herbal preparations studied here are prepared the way they are usually drunk, Ip displays the highest inhibition of protein nitration, and the highest promotion of cell survival, whereas green tea or red wines display significant but lesser effects at the same concentrations. Further studies aiming at isolation of the active principles and assessment of their bioavailability are warranted.
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Naturalistic research methods have been developed to collect data in the daily environment, providing ecological valid measures. Recent reports suggest, however, that compliance with fixed time sampling protocols may be problematic and can bias results. This study investigated compliance with an intensive, random time sampling protocol for salivary cortisol and effects of non-compliance on cortisol results. ⋯ Contrary to previous reports, inclusion of non-compliant samples in the analysis did not distort the cortisol diurnal profile. Intensive, random time sampling appears to have advantages over fixed time sampling for obtaining valid cortisol profiles when researchers do not have devices to monitor compliance. Results indirectly support the validity of momentary self-report data about daily experiences obtained with the same sampling methods.
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Cerebral salt wasting (CSW) frequently occurs concomitantly with aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces total blood volume. As a result, the risk of symptomatic cerebral vasospasm may be elevated. ⋯ This study demonstrated for the first time that a rat SAH model exhibited CSW. It was suggested that the cause of CSW was neither ANP nor BNP. In addition, this rat SAH model will be useful for study of CSW after SAH.