Ultrafast electronic state conversion at room temperature utilizing hidden state in cuprate ladder system.

Photo-control of material properties on femto- (10(-15)) and pico- (10(-12)) second timescales at room temperature has been a long-sought goal of materials science. Here we demonstrate a unique ultrafast conversion between the metallic and insulating state and the emergence of a hidden insulating state by tuning the carrier coherence in a wide temperature range in the two-leg ladder superconductor Sr(14-x)Ca(x)Cu24O41 through femtosecond time-resolved reflection spectroscopy. We also propose a theoretical scenario that can explain the experimental results. The calculations indicate that the holes injected by the ultrashort light reduce the coherence among the inherent hole pairs and result in suppression of conductivity, which is opposite to the conventional photocarrier-doping mechanism. By using trains of ultrashort laser pulses, we successively tune the carrier coherence to within 1 picosecond. Control of hole-pair coherence is shown to be a realistic strategy for tuning the electronic state on ultrafast timescales at room temperature.

Facilitated nitration and oxidation of LDL in cigarette smokers.

BACKGROUND: Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking-induced oxidative stress is considered to favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers. MATERIALS AND METHODS: Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion-exchange high-performance liquid chromatography (AE-HPLC) and measurements of thiobarbituric acid-reactive substances (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), vitamin E, 3-nitrotyrosine and 3-chlorotyrosine. RESULTS: Smokers showed a significantly higher level of TBARS and 8-OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3-nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3-chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption. CONCLUSION: The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.

Information gain in an optical bistable system by stochastic resonance.

We have shown an experimental demonstration of information gain due to the stochastic resonance in an optical bistable system, that is, information hidden in the input wave form appears in the output of a nonlinear system when the input noise amplitude is adequate. The optical bistable system is a hybrid type comprising a LiNbO3 crystal with an electric feedback loop, and the input of the system is the sum of a binary bit series and a Gaussian colored noise. The information gain is proved to be prominent when the noise cutoff frequency is larger than the bit rate.

Ginkgo biloba extract-induced relaxation of rat aorta is associated with increase in endothelial intracellular calcium level.

Ginkgo biloba extract (GBE) has been used clinically for improving peripheral vascular diseases in France and Germany. In the present study, to clarify the pharmacological properties of vasodilation produced by GBE, we examined the effect of GBE and quercetin, one of the ingredients in GBE, on the thoracic aorta isolated from Wistar rats. GBE produced a dose-dependent relaxation in the aortic ring precontracted with noradrenaline, and the relaxation was abolished by L-N(G)-nitro arginine methyl ester (L-NAME). Quercetin produced a similar relaxation, which was also abolished by L-NAME. We then examined the effects of GBE and quercetin on the intracellular calcium level ([Ca2+]i) of cultured aortic endothelial cells using a fluorescent confocal microscopic imaging system. Both GBE and quercetin produced significant increases in [Ca2+]i in the endothelial cells. The increase in [Ca2+]i by quercetin (10(-6) M) was abolished by removing the extracellular Ca2+, but was not affected by thapsigargin, a calcium pump inhibitor. These findings suggest that a principal ingredient of GBE producing vasodilation is quercetin, which can activate nitric oxide synthesis and release by increasing [Ca2+]i in vascular endothelial cells.

Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats.

1. Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO) - cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR). 2. Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks. 3. In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY. 4. In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake. 5. Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake. 6. These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway.

Participation of ATP in cell volume regulation in the endothelium after hypotonic stress.

1. The role of ATP in the regulatory volume decrease (RVD) after hypotonic cell swelling was examined in cultured endothelial cells isolated from the rat caudal artery. 2. Hypotonic stress increased [Ca2+]i in addition to increasing the overflow of ATP and cell volume. The hypotonicity induced increase in [Ca2+]i was prevented by pyridoxalphosphate-6-azophenyl-1-2',4'-disulphonic acid (PPADS; a P2 purinoceptor antagonist), U-73122 (a phospholipase C inhibitor) and thapsigargin (a Ca2+ pump inhibitor). However, the hypotonicity induced increase in cell volume was potentiated by PPADS, U-73122 and thapsigargin. 3. Similar changes were observed in cells treated with 2-methylthioATP, a P2Y purinoceptor agonist, but not by alpha,beta-methylene ATP, a P2X purinoceptor agonist. Thus, it appears that the responses observed following hypotonic stress are mediated by activation of P2Y purinoceptors. 4. On the basis of these findings, it is suggested that ATP, which is released by hypotonicity, may participate in the RVD as a substantial regulator or initiator via P2 purinoceptor-induced increases in [Ca2+]i.

Role of 5-HT(2) receptor subtypes in depletion of 5-HT induced by p-chloroamphetamine in the mouse frontal cortex.

A serotonin (5-hydroxytryptamine, 5-HT)-releasing drug, p-chloroamphetamine elicited decreases in 5-HT levels in the mouse frontal cortex. 5-HT reduction elicited by p-chloroamphetamine was inhibited by the 5-HT(2A/2B/2C) receptor antagonist, LY 53857 and the 5-HT(2A) receptor antagonist, ketanserin. However, the 5-HT(2B/2C) receptor antagonist, SB 206553, enhanced it. LY 53857 and ketanserin can inhibit hyperthermia elicited by p-chloroamphetamine, although SB 206553 enhances it. The effects of the 5-HT(2) receptor antagonists on neurotoxicity are very similar to those on hyperthermia. Since hyperthermia facilitates neurotoxicity induced by amphetamine analogue, these 5-HT(2) receptor antagonists may modify 5-HT depletion induced by p-chloroamphetamine through responses to body temperature.

Oxidants in cigarette smoke extract modify low-density lipoprotein in the plasma and facilitate atherogenesis in the aorta of Watanabe heritable hyperlipidemic rabbits.

Epidemiological studies have shown that cigarette smoking is a major cause of atherosclerosis. Oxidants as well as nicotine in cigarette smoke have been implicated in atherogenesis. To clarify the mechanism involved, we examined the chronic effects of nicotine and nicotine-free cigarette smoke extracts (CSE) on oxidative modification of low-density lipoprotein (LDL) in the plasma of Watanabe heritable hyperlipidemic rabbits and atherogenesis in the aorta. CSE was prepared by bubbling the gas phase of smoke (1 ml/three cigarettes) into phosphate buffer saline, and 3 ml of this CSE was injected daily into the ear vein of the rabbit for five months. The rabbits treated with CSE showed an increase in lipid peroxide levels, estimated as thiobarbituric acid reactive substances (TBARS), with a corresponding decrease in vitamin E levels in the plasma. They also showed enhanced oxidative modification of LDL, assessed by anion-exchange HPLC, incorporation into macrophages and measurement of TBARS. These events could be efficiently prevented by administering vitamin E (150 mg/kg/day, p.o.). Nicotine alone (0.5 mg/kg/day, s.c.) led to a temporary increase in the plasma triglyceride level. At the end of the experiment, CSE but not nicotine had caused progression of atherosclerotic lesions together with accumulation of cholesteryl ester in the thoracic aorta, while vitamin E had significantly prevented such atheromatous formation. These results indicate that oxidants in CSE can promote the development of atherosclerosis through oxidative modification of plasma LDL, particularly in hypercholesterolemia, and offer evidence for increased vitamin E utilization in smokers.

Nicorandil--induced ATP release in endothelial cells of rat caudal artery is associated with increase in intracellular Ca(2+).

The effect of nicorandil, an ATP-sensitive K(+) channel opener, on the level of intracellular Ca(2+) ([Ca(2+)](i)) and on ATP release in endothelial cells of the rat caudal artery was examined using a fluorescent confocal microscopic imaging system and high-performance liquid chromatography (HPLC) with fluorescent detection, respectively. Nicorandil significantly increased [Ca(2+)](i) and the overflow of ATP and its metabolites. The former reaction was abolished in the absence of extracellular Ca(2+), but it did not change in the presence of thapsigargin or cyclopiazonic acid. The increase in the overflow of ATP and [Ca(2+)](i) induced by nicorandil was markedly suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. The increase of [Ca(2+)](i) induced by nicorandil was significantly and inversely correlated with the level of intracellular ATP in the endothelial cells, suggesting that activation of ATP-sensitive K(+) channels by nicorandil increases Ca(2+) influx in endothelial cells. The increase of [Ca(2+)](i) might be associated with ATP release.

2-Arachidonoylglycerol, a candidate of endothelium-derived hyperpolarizing factor.

We investigated whether 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, is involved in acetylcholine- and calcium ionophore A23187-induced relaxations in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin, which is considered to be mediated by endothelium-derived hyperpolarizing factor (EDHF). In rabbit mesenteric arterial rings pre-constricted with noradrenaline, 2-arachidonoylglycerol caused concentration-dependent relaxation. The 2-arachidonoylglycerol-induced relaxations were not affected by endothelium removal. N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-caroxamide (SR141716A) and 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morholinyl-1H-pyrazole-3-carboxamide (AM281), cannabinoid CB(1) receptor antagonists, significantly attenuated 2-arachidonoylglycerol-induced relaxation and the acetylcholine-induced relaxation only slightly, but not the calcium ionophore A23187-induced relaxation. On the other hand, charybdotoxin plus apamin, K(+) channel blockers, significantly attenuated acetylcholine and calcium ionohore A23187-induced relaxations but not 2-arachidonoylglycerol-induced relaxations. These results suggest that 2-arachidonoylglycerol can cause relaxations via cannabinoid CB(1) receptors, but is not involved in EDHF-mediated relaxations.

Anion-exchange high-performance liquid chromatography assays of plasma lipoproteins and modified low-density lipoproteins using a ProtEx-DEAE column.

Previously [Anal. Biochem., 232 (1995) 163-171], we reported a high-performance liquid chromatography (HPLC) assay method for human plasma lipoproteins using a diethylaminoethyl (DEAE)-glucomannan column, which is not commercially available. In this study, HPLC assay methods for lipoproteins in plasma samples of human and experimental animals, and modified low-density lipoproteins (LDLs) of rabbits have been developed using a commercially available anion-exchange ProtEx-DEAE column. For the assays of plasma lipoproteins, the method includes complete separation of high-density lipoproteins, LDLs and very low-density lipoproteins within 20 min using stepwise elution, and determination by post-column reaction with an enzymatic cholesterol reagent as the total cholesterol (TC) level. Similarly, mild oxidative and artificially oxidised LDLs were separated into their subfractions using stepwise elution, and determined based on the TC level. The methods using the DEAE-glucomannan and ProtEx-DEAE columns were cross-validated. There was an excellent correlation between the two methods. The obtained results reveal that the anion-exchange HPLC method using the ProtEx-DEAE column could be useful for the assays of plasma lipoproteins and modified LDLs.

Effect of 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine on noradrenaline release from vascular sympathetic nerves.

1. The effects of 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine (HAK2701), a selective and potent ligand for P3 receptor-like protein, on the release of endogenous noradrenaline (NA) from electrically stimulated rat mesenteric artery and rabbit ear artery were compared with those of a number of purinoceptor agonists. 2. In the rat mesenteric artery, the P1 receptor agonists 2-chloroadenosine (2CA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the P2 purinoceptor agonists beta,gamma-methylene ATP (betagammamATP) and 2-methylthio ATP (2mSATP) significantly inhibited the release of NA in a xanthine-sensitive manner. HAK2701 did not significantly inhibit the release of NA, the relative order of potency being betagammamATP > NECA > 2CA > 2mSATP >> HAK2701. 3. In the rabbit ear artery, both P1 and P2 receptor agonists significantly facilitated the release of NA in a xanthine-sensitive manner. HAK2701 also significantly facilitated the release of NA, the relative order of potency being HAK2701 > betagammamATP > 2CA > 2mSATP > NECA. 4. These findings suggest that HAK2701 may be a potent and selective agonist for facilitatory prejunctional purinoceptors, but not for inhibitory purinoceptors, on adrenergic nerve terminals.

Characterization of prejunctional purinoceptors inhibiting noradrenaline release in rat mesenteric arteries.

The effects of purinoceptor agonists on noradrenaline NA release by electrical stimulation in rat mesenteric arteries were examined to clarify the pharmacological properties of prejunctional purinoceptors on adrenergic nerves. Adenosine and the other P1-receptor agonists, 5'-(N-ethylcarboxamido) adenosine and 2-chloroadenosine, significantly inhibited the release of NA. Also beta,gamma-methylene ATP and 2-methylthio ATP, P2-receptor agonists, significantly inhibited NA releases. The inhibitory effect of adenosine was significantly reduced by adenosine deaminase, but those of beta,gamma-methylene ATP and 2-methylthio ATP were not affected. This suggests that the inhibitory effects of P2-receptor agonists are not due to conversion into adenosine. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), a P1 (A1)-receptor antagonist, significantly reduced the inhibitory effects of not only the P1- but also P2-receptor agonists. Therefore, DPCPX appears to act on both prejunctional P1- and P2-receptor as an antagonist. Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), a P2-receptor antagonist, significantly reduced the inhibitory effects of the P2-receptor agonists, but not those of the P1-receptor agonists. From these findings in the rat mesenteric artery, the P1-receptor agonist-induced inhibition of NA-release appears to be mediated via a well-known prejunctional P1-receptor of the A1-subtype, but the P2-receptor agonist-induced inhibition appears to be mediated via an unidentified purinoceptor that is blocked not only by P2-receptor antagonists but also by P1-receptor antagonists.

Suitable indices for evaluating the intensity of tumor metastasis in a mouse experimental metastatic model.

We investigated the time course of developmental changes of tumor metastasis in mice intravenously inoculated with B16-F10 melanoma cells. The mice showed a normal blood profile at 7 and 14 days after the injection, while at 21 days they developed severe anemia and thrombocytopenia. The number of metastatic lung nodules in the mice at 7 and 14 days after the cell injection was 68 +/- 12 and 326 +/- 39 (mean +/- S. E. of 5 mice), respectively, while it could not be accurately counted at 21 days owing to a fusion of the nodules. The wet weight and the melanin content of the lung markedly increased at 21 days. These results suggest that an abnormal blood profile, lung weight and the melanin content of the lung are suitable indices for the late stage of the experimental metastatic model, while the number of lung nodules is suitable for the early stage.

Altered endothelium-dependent responsiveness in the aortas and renal arteries of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus.

We examined endothelium-dependent relaxation in the aortas and renal arteries of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus, in comparison with non-diabetic Long-Evans Tokushima Otsuka rats as controls. Acetylcholine-induced relaxation in both arteries was attenuated, and the attenuation was restored to the control level by indomethacin. The relaxation was inhibited completely in the aortas, but only partially in renal arteries by N(G)-nitro-L-arginine methyl ester, and the degree of the latter inhibition was greater in OLETF rats than in the controls. The relaxation was inhibited by aminoguanidine in both arteries of OLETF rats but not in the controls. Serum NO(2) plus NO(3) levels significantly increased in OLETF rats. These results suggest that impairment of relaxation in OLETF rat arteries is due to increased release of contractile factors but not decreased release of nitric oxide.

Inhibitory effects of water extracts from fruiting bodies of cultured Cordyceps sinensis on raised serum lipid peroxide levels and aortic cholesterol deposition in atherosclerotic mice.

We investigated the effects of the water extracts of the fruiting bodies of cultured Cordyceps sinensis (WECS) on lipid metabolism in mice fed an atherogenic diet. WECS was orally administered at doses of 50, 100 and 200 mg/kg/day for 12 weeks. WECS showed no toxic effects on the growth rate, liver or kidney weights of the mice. Mice fed the atherogenic diet showed marked increases in serum lipid and lipid peroxide levels and also aortic cholesterol levels, particularly cholesteryl ester level, a major lipid constituent in atherosclerotic lesions. WECS significantly suppressed the increased serum lipid peroxide level but not other lipid levels in a dose-dependent manner. WECS also suppressed the increased aortic cholesteryl ester level in a dose-dependent manner. These results suggest that WECS prevents cholesterol deposition in the aorta by inhibition of LDL oxidation mediated by free radicals rather than by reduction in serum lipid level. WECS may exert beneficial effects on the formation of the atherosclerotic lesion induced by oxidative stress with few side effects.

Antioxidant activity of the extracts from fruiting bodies of cultured Cordyceps sinensis.

Cordyceps sinensis is one of the most valued herbs in traditional Chinese medicine. We investigated the antioxidant activities of the cultured fruiting bodies of Cordyceps sinesis. The water and ethanol extracts of Cordyceps sinensis were found to possess a potent antioxidant activity. The scavenging effects of the extracts on superoxide were very weak, but the extracts moderately inhibited malondialdehyde formation via hydroxyl radical induced by SIN-1, a peroxynitrite generator. Of the extracts examined, the hot water extract (70 degrees C for 5 min) showed the greatest oxygen free radical scavenging activity. Also, when low-density lipoprotein (LDL) was incubated with macrophages in the presence of CuCl2 (1 microM), the hot water extract showed a strong inhibitory effect against lipid peroxidation in the medium and consequent accumulation of cholesteryl ester in macrophages. Their activities were comparable to that of authentic Cu/Zn SOD. These results suggest that the extracts of cultured Cordyceps sinensis possess potent antioxidant and anti-lipid peroxidation activities and inhibit accumulation of cholesteryl ester in macrophages via suppression of LDL oxidation.

Evidence of modified LDL in the plasma of hypercholesterolemic WHHL rabbits injected with aqueous extracts of cigarette smoke.

Cigarette smoking is a major risk factor for atherosclerosis, and oxidative modification of low density lipoprotein (LDL) is a key event in the development of atherosclerosis. The aim of the present study was to determine whether modified LDL would be formed in the plasma of Watanabe heritable hyperlipidemic (WHHL) rabbits injected with nicotine-free cigarette smoke extracts (CSE). In order to assess this, cigarette smoke-modified LDL (CS-LDL) was prepared by incubation of rabbit native LDL (N-LDL) with CSE for 24 h. The oxidative modification in CS-LDL was well established by the reduced ratio between two LDL subfractions (LDL2/LDL3) separated by anion-exchange HPLC, together with the fast migration in the anodic direction in agarose gel electrophoresis and the increased lipid peroxide levels. Very similar modification was noted with mildly oxidatively modified LDL prepared by incubation of N-LDL with 5 µM CuCl(2) for 1 h. When WHHL rabbits (n=4) intravenously received a single injection of CSE, the ratio of LDL2/LDL3 was markedly reduced compared with the control rabbits (n=4) while total cholesterol levels in the plasma gradually decreased until 24 h after the injection. These results suggest that oxidatively modified LDL, probably like CS-LDL, is produced in the plasma of WHHL rabbits injected with CSE.

A nitric oxide synthase inhibitor reduces hyperphagia induced in rats by the 5-HT(1A) receptor agonist, 8-OH-DPAT, independently of hypothalamic serotonin metabolism.

In rats, a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) inhibited the hyperphagia induced by the 5-hydroxytryptamine (5-HT)(1A) autoreceptor agonist, 8-hydroxy-2-di-n-(propylamino)tetralin (8-OH-DPAT). 8-OH-DPAT reduced 5-HT metabolism in the hypothalamus, and this was not blocked by pretreatment with L-NAME. L-NAME also did not affect basal hypothalamic 5-HT metabolism or reverse the decreases in 5-HT synthesis in hypothalamus. These results suggest that the hypophagic effects of L-NAME, which inhibits NO formation, are independent of 5-HT metabolism in the hypothalamus.