Life sciences
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Although the understanding of migraine pathophysiology is still incomplete, there seems to be little doubt that dilatation of cranial blood vessels, including meningeal arteries, is involved in the headache phase of migraine. Since calcitonin gene-related peptide (CGRP) has been implicated in this vasodilatation, the present study set out to compare the relaxant effects of the endogenous ligand h-alphaCGRP, and [ethylamide-Cys(2,7)]h-alphaCGRP ([Cys(Et)(2,7)]h-alphaCGRP), a CGRP(2) receptor agonist, on human isolated middle meningeal artery segments, precontracted with KCl. Classical Schild plot analysis was used to characterise the receptor population in this artery using BIBN4096BS and h-alphaCGRP(8-37) as antagonists. h-alphaCGRP relaxed arterial segments more potently than [Cys(Et)(2,7)]h-alphaCGRP (pEC(50): 8.51+/-0.16 and 7.48+/-0.24, respectively), while the maximal responses to these agonists were not significantly different. ⋯ Furthermore, the results obtained from RT-PCR studies confirmed the presence of all the essential components required for a functional CGRP(1) receptor in these arteries. Considering the high antagonist potency of BIBN4096BS, coupled to the lower agonist potency of [Cys (Et)(2,7)]h-alphaCGRP, it is reasonable to suggest a predominant role of CGRP(1) receptors in the human middle meningeal artery. This view is reinforced by Schild plot analysis, which revealed a slope of unity in all experiments, giving further evidence for a homogeneous CGRP receptor population in this vascular preparation.
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The aim of the present study was to determine whether the clinically effective cardioprotection conferred by puerarin (Pue) against ischemia and reperfusion is mediated by mitochondrial transmembrane pores and/or channels. Hearts isolated from male Sprague-Dawley rats were perfused on a Langendorff apparatus and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The production of formazan, which provides an index of myocardial viability, was measured by absorbance at 550 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was determined. ⋯ In mitochondria isolated from hearts pretreated with 0.24 mmol/l Pue for 5 min, a significant inhibition of Ca(2+)-induced swelling was observed, and this inhibition was attenuated by 5-hydroxydecanoate. In isolated ventricular myocytes, pretreatment with Pue prevented ischemia-induced cell death and depolarization of the mitochondrial membrane, and atractyloside and 5-hydroxydecanoate attenuated the effects of Pue. These findings indicate that puerarin protects the myocardium against ischemia and reperfusion injury via inhibiting mitochondrial permeability transition pore opening and activating the mitochondrial ATP-sensitive potassium channel.
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There is an emerging body of data suggesting that mood disorders are associated with decreased brain-derived neurotrophic factor (BDNF). The present study aims to investigate the effects of the mood stabilizers lithium (Li) and valproate (VPT) in an animal model of bipolar disorder. In the first experiment (acute treatment), rats were administered D-amphetamine (AMPH) or saline for 14 days, and then between day 8 and 14, rats were treated with either Li, VPT or saline. ⋯ In the first experiment, Li increased BDNF levels in rat hippocampus. In the second experiment, AMPH decreased BDNF levels and Li and VPT increased BDNF levels in rat hippocampus. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
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High density lipoprotein (HDL) binds lipopolysaccharide (LPS) and neutralizes its toxicity. The aim of our study was to investigate the effects of Apolipoprotein (ApoA-I), the major apolipoprotein of HDL, on LPS-induced acute lung injury (ALI) and endotoxemia. BALB/c mice were challenged with LPS, followed by ApoA-I or saline administration for 24h. ⋯ Furthermore, we investigated in vivo the effects of ApoA-I on the mortality rate and survival time after LPS administration and found that ApoA-I significantly decreased the mortality (P<0.05) and increased the survival time (P<0.05). In summary, the results suggest that ApoA-I could effectively protect against LPS-induced endotoxemia and acute lung damage. The mechanism might be related to inhibition of inflammatory cytokine release from macrophages.